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Sample records for age 5y 5mo

  1. Dietary protein intake is associated with body mass index and weight up to 5 y of age in a prospective cohort of twins12

    PubMed Central

    Pimpin, Laura; Jebb, Susan; Johnson, Laura; Wardle, Jane

    2016-01-01

    Background: Few large epidemiologic studies have investigated the role of postweaning protein intake in excess weight and adiposity of young children, despite children in the United Kingdom consistently consuming protein in excess of their physiologic requirements. Objective: We investigated whether a higher proportion of protein intake from energy beyond weaning is associated with greater weight gain, higher body mass index (BMI), and risk of overweight or obesity in children up to 5 y of age. Design: Participants were 2154 twins from the Gemini cohort. Dietary intake was collected by using a 3-d diet diary when the children had a mean age of 21 mo. Weight and height were collected every 3 mo, from birth to 5 y. Longitudinal models investigated associations of protein intake with BMI, weight, and height, with adjustment for age at diet diary, sex, total energy intake, birth weight/length, and rate of prior growth and clustering within families. Logistic regression investigated protein intake in relation to the odds of overweight or obesity at 3 and 5 y of age. Results: A total of 2154 children had a mean ± SD of 5.7 ± 3.2 weight and height measurements up to 5 y. Total energy from protein was associated with higher BMI (β = 0.043; 95% CI: 0.011, 0.075) and weight (β = 0.052; 95% CI: 0.031, 0.074) but not height (β = 0.088; 95% CI: −0.038, 0.213) between 21 mo and 5 y. Substituting percentage energy from fat or carbohydrate for percentage energy from protein was associated with decreases in BMI and weight. Protein intake was associated with a trend in increased odds of overweight or obesity at 3 y (OR = 1.10; 95% CI 0.99, 1.22, P = 0.075), but the effect was not statistically significant at 5 y. Conclusion: A higher proportion of energy from protein during the complementary feeding stage is associated with greater increases in weight and BMI in early childhood in this large cohort of United Kingdom children. PMID:26718416

  2. Immunological persistence in 5 y olds previously vaccinated with hexavalent DTPa-HBV-IPV/Hib at 3, 5, and 11 months of age.

    PubMed

    Silfverdal, Sven A; Assudani, Deepak; Kuriyakose, Sherine; Van Der Meeren, Olivier

    2014-01-01

    The combined diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis/Haemophilus influenza vaccine (DTPa-HBV-IPV/Hib: Infanrix™ hexa, GlaxoSmithKline Vaccines) is used for primary vaccination of infants in a range of schedules world-wide. Antibody persistence after 4 DTPa-HBV-IPV/Hib doses in the first 2 y of life has been documented, but long-term persistence data following the 3, 5, 11-12 months (3-5-11) infant vaccination schedule, employed for example in Nordic countries, are limited. We assessed antibody persistence in 57 5-year-old children who had received either DTPa-HBV-IPV/Hib or DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in the 3-5-11 schedule. Among DTPa-HBV-IPV/Hib recipients, 7/12 retained seroprotective antibody concentrations for diphtheria, 10/12 for tetanus, 5/12 for hepatitis and 10/12 for Hib. Detectable antibodies were observed for 0/12 children for pertussis toxin (PT), 12/12 for filamentous haemagglutinin (FHA) and 8/12 for pertactin (PRN). Among DTPa-IPV/Hib recipients, 28/45 retained seroprotective anti-diphtheria concentrations, 34/44 for tetanus and 40/45 for Hib. Detectable antibodies were observed for 9/45 children for PT, 41/45 for FHA and 34/45 for PRN. Antibody persistence in DTPa-HBV-IPV/Hib and DTPa-IPV/Hib-vaccinees appeared similar in 5 y olds to that previously observed in children of a similar age who had received 4 prior doses of DTPa-HBV-IPV/Hib (or DTPa-IPV/Hib). As in subjects primed with 4 prior doses, we observed that antibodies markedly declined by 5 y of age, calling for the administration of a pre-school booster dose in order to ensure continued protection against pertussis. PMID:25483640

  3. Layer structure: The oxides A 3Ti 5MO 14

    NASA Astrophysics Data System (ADS)

    Hervieu, M.; Rebbah, H.; Desgardin, G.; Raveau, B.

    1980-11-01

    Five new oxides, K 3Ti 5MO 14, Rb 3Ti 5MO 14 ( M = Ta, Nb), and Tl 3Ti 5NbO 14, have been synthesized. The structure of these oxides consists of octahedral layers similar to those observed for Na 2Ti 3O 7 and held together by monovalent ions; the sheets consist of blocks of 2 × 3 edge-sharing octahedra, which are then joined to each other by the corners of the octahedra. The relative disposition of the layers is similar to that observed for Tl 2Ti 4O 9. These oxides can be considered as the member n = 3 of a series of closely related structures with formula AnB2 nO 4 n+2 , where n indicates the number of octahedra which determines the width of the blocks of 2 × n octahedra.

  4. Dietary intake of soluble fiber and risk of islet autoimmunity by 5 y of age: results from the TEDDY study12

    PubMed Central

    Beyerlein, Andreas; Liu, Xiang; Uusitalo, Ulla M; Harsunen, Minna; Norris, Jill M; Foterek, Kristina; Virtanen, Suvi M; Rewers, Marian J; She, Jin-Xiong; Simell, Olli; Lernmark, Åke; Hagopian, William; Akolkar, Beena; Ziegler, Anette-G; Krischer, Jeffrey P; Hummel, Sandra

    2015-01-01

    Background: Deficient soluble fiber intake has been suggested to dysregulate the immune response either directly or through alterations of the microbial composition in the gut. Objective: We hypothesized that a high intake of dietary soluble fiber in early childhood decreases the risk of type 1 diabetes (T1D)–associated islet autoimmunity. Design: We analyzed 17,620 food records collected between age 9 and 48 mo from 3358 children from the United States and Germany prospectively followed in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. HRs for the development of any/multiple islet autoantibodies (242 and 151 events, respectively) and T1D (71 events) by soluble fiber intake were calculated in Cox regression models and adjusted for potential confounders. Results: There were no statistically significantly protective associations observed between a high intake of soluble fiber and islet autoimmunity or T1D. For example, the adjusted HRs (95% CIs) for high intake (highest compared with lowest quintile) at age 12 mo were 0.90 (0.55, 1.45) for any islet autoantibody, 1.20 (0.69, 2.11) for multiple islet autoantibodies, and 1.24 (0.57, 2.70) for T1D. In analyzing soluble fiber intake as a time-varying covariate, there were also no short-term associations between soluble fiber intake and islet autoimmunity development, with adjusted HRs of 0.85 (0.51, 1.42) for high intake and development of any islet autoantibody, for example. Conclusion: These results indicate that the intake level of dietary soluble fiber is not associated with islet autoimmunity or T1D in early life. PMID:26156735

  5. Postnatal weight and height growth velocities at different ages between birth and 5 y and body composition in adolescent boys and girls

    PubMed Central

    Botton, Jérémie; Heude, Barbara; Maccario, Jean; Ducimetière, Pierre; Charles, Marie-Aline

    2008-01-01

    Background Rapid weight gain in the first years of life is associated with adult obesity. Whether there are critical windows for this long term effect is unclear. Objective To study anthropometry in adolescence by gender according to weight and height growth velocities at different ages between birth and five years. Design Anthropometric parameters, including fat and fat-free mass by bipodal impedancemetry, were measured in 468 8–17 year old adolescents. We retrospectively collected early infancy data and individually estimated weight and height growth velocities in 69.4% of them using a mathematical model. Associations between birth parameters, growth velocities and anthropometric parameters in adolescence were studied. Results Weight growth velocity at three months was associated with overweight (OR for a 1 SD increase [95% CI]=1.52[1.04–2.22]), fat mass and waist circumference in adolescence in both genders, and with fat-free mass only in boys (r=0.29, P<0.001 versus r=−0.01, ns in girls). Weight growth velocities after 2 years were associated with all anthropometric parameters in adolescence, in both genders. Between 6 months and 2 years, weight growth velocities were significantly associated only with adolescent height in boys; in girls, associations with fat mass in adolescence were weaker. Discussion Our results support the hypothesis of two critical windows in early childhood associated with the later risk of obesity: up to 6 months and from 2 years onwards. The study of the determinants of growth during these two periods is of major importance for the prevention of obesity in adolescence. PMID:18541566

  6. Structure and properties of Y 5Mo 2O 12 and Gd 5Mo 2O 12: Mixed valence oxides with structurally equivalent molybdenum atoms

    NASA Astrophysics Data System (ADS)

    Torardi, C. C.; Fecketter, C.; McCarroll, W. H.; DiSalvo, F. J.

    1985-12-01

    Crystals of Ln5Mo 2O 12 ( Ln = Y, Gd) were grown by electrochemical reduction of alkali-molybdate/rare-earth oxide melts at 1075-1100°C. A single crystal of Y 5Mo 2O 12, used for structure determination, was found to be monoclinic with a = 12.2376(7) Å, b = 5.7177(8) Å, c = 7.4835(5) Å, β = 108.034(5)°, and Z = 2. Although the structure was refined in space group {C2}/{m}, the true space group appears to be {P2 1}/{m}. In Y 5Mo 2O 12, rutile-like sheets of edge-shared MoO 6 chains linked by YO 6 octahedra are interconnected with YO 7 monocapped trigonal prisms. The Mo atoms in the chains have alternating distances of 2.496 and 3.221 Å and in that respect are similar to MoO 2. However, in contrast to metallic MoO 2 both the Y and Gd compounds are n-type semiconductors with room temperature resistivities of the order of 10 3 ohm-cm. Magnetic susceptibility measurements confirm the presence of one unpaired electron per Mo 2 unit. The semiconducting behavior can be explained in terms of an unfavorable bridging oxygen coordination which prevents electron delocalization through metal-oxygen pi bonding as in MoO 2.

  7. Thermophysical properties of Ti-5Al-5V-5Mo-3Cr-1Zr titanium alloy

    NASA Astrophysics Data System (ADS)

    Bykov, V. A.; Kulikova, T. V.; Vedmid', L. B.; Fishman, A. Ya.; Shunyaev, K. Yu.; Tarenkova, N. Yu.

    2014-07-01

    The thermophysical properties of the Ti-5Al-5V-5Mo-3Cr-1Zr titanium alloy in a wide range of temperatures from room temperature to 1000°C have been studied by the methods of differential scanning calorimetry, the laser flash method, and dilatometry. The obtained data on heat capacity, thermal diffusivity, and thermal expansion have been used for calculating coefficient of thermal conductivity. The sequence and temperatures of structural transformations during heating of the alloy have been established. It has been shown that the studied alloy possesses a coefficient of thermal conductivity that is 3.5-4 times smaller than that of pure titanium.

  8. Surface modification of a Ti-7.5Mo alloy using NaOH treatment and Bioglass coating.

    PubMed

    Ho, Wen-Fu; Lai, Chien-Hung; Hsu, Hsueh-Chuan; Wu, Shih-Ching

    2010-05-01

    The objective of this study was to propose a surface modification for a low-modulus Ti-7.5Mo alloy to initiate the formation of hydroxyapatite (HA) during in vitro bioactivity tests in simulated body fluid (SBF). Specimens of commercially pure titanium (c.p. Ti) and Ti-7.5Mo were initially immersed in a 15 M NaOH solution at 60 degrees C for 24 h, resulting in the formation of a porous network structure composed of sodium titanate (Na(2)Ti(5)O(11)). Afterwards, bioactive Bioglass particles were deposited on the surface of NaOH-treated c.p. Ti and Ti-7.5Mo. The specimens were then immersed in SBF at 37 degrees C for 1, 7 and 28 days, respectively. The apatite-forming ability of the NaOH-treated and Bioglass-coated Ti-7.5Mo was higher than that of the c.p. Ti under the same condition. The X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS) results indicated that the deposited amounts of calcium phosphate were much greater for the surface-treated Ti-7.5Mo than for the c.p. Ti, a finding attributable to or correlated with the higher pH value of the SBF containing surface-treated Ti-7.5Mo. Moreover, in the surface-treated Ti-7.5Mo, the pH value of the SBF approached a peak of 7.66 on the first day. A combination of NaOH treatment and subsequent Bioglass coating was successfully used to initiate in vitro HA formation in the surface of the Ti-7.5Mo alloy. PMID:20069344

  9. Advanced glycation end products induce oxidative stress and mitochondrial dysfunction in SH-SY5Y cells.

    PubMed

    Wang, Xu; Yu, Song; Wang, Chun-Yan; Wang, Yue; Liu, Hai-Xing; Cui, Yong; Zhang, Li-De

    2015-02-01

    This study aimed to investigate the direct effects of advanced glycation end products (AGEs) on the mitochondrial structure and function of SH-SY5Y cells and the possible molecular mechanism(s) underlying mitochondria dysfunction by AGEs. SH-SY5Y cells were cultured in 400 μg/ml of AGE-bovine serum albumin (BSA) for 24 h, and changes in the mitochondrial function of SH-SY5Y cells were analysed as follows. Reactive oxygen species (ROS) were detected using 2',7'-dichlorodihydrofluorescein diacetate molecular probes. Mitochondrial membrane potential (ΔΨm) was determined by flow cytometry using fluorescent probes. The expression of cytochrome c (Cyt c) protein level was assessed by Western blotting. Mitochondrial structures were observed by transmission electron microscopy. Our results showed that AGE-BSA induced an increase in ROS levels, a decrease in mitochondrial ΔΨm, and the release of Cyt c from mitochondria in SH-SY5Y cells. The mitochondria of SH-SY5Y cells showed remarkable swelling and vacuolisation, but these changes were recovered after pretreatment with neutralising anti-receptor for advanced glycation end products (RAGE) antibody. Our results suggested that AGE-BSA induced mitochondrial dysfunction in SH-SY5Y cells through RAGE pathways. Thus, AGEs are potential mechanistic links between diabetes mellitus and Alzheimer's disease. PMID:25381033

  10. Effect of tempering temperature on properties of 00Cr16Ni5Mo stainless steel

    SciTech Connect

    Qin, B. Wang, Z.Y.; Sun, Q.S.

    2008-08-15

    Specimens of 00Cr16Ni5Mo low carbon martensitic stainless steel were normalized at 1000 deg. C followed by tempering at 525 deg. C, 550 deg. C, 575 deg. C, 600 deg. C and 625 deg. C. After heat treatment, mechanical properties and pitting potential were determined through tensile, impact and electrochemical polarization tests. The results showed that the samples tempered at 550 deg. C and 600 deg. C for 2 h had an excellent combination of tensile strength, elongation, impact energy, hardness and corrosion resistance. Scanning electron microscopy, and X-ray diffraction examinations were conducted. These revealed that the properties of the steel were affected by the structure of the lath martensite, {delta}-ferrite, retained austenite and carbides.

  11. Synthesis of CORONA 5 (Ti-4.5Al-5Mo-1.5Cr)

    NASA Astrophysics Data System (ADS)

    Froes, F. H.; Highberger, W. T.

    1980-05-01

    The synthesis of CORONA 5 (Ti-4.5Al-5Mo-1.5Cr) is described from the viewpoints of alloy chemistry and microstructure. Lenticular alpha is shown to maximize fracture resistance parameters, while a globular alpha optimizes hightemperature flow characteristics. The processing and application of CORONA 5 as forging, plate, sheet and powder metallurgy products are presented. The weldability of the alloy is described and potential use of the alloy for engine applications discussed. The improved mechanical property behavior over the "workhorse" Ti-6Al-4V alloy combined with cost-effective production should result in use of CORONA 5 in many applications. Future developments for CORONA 5 are suggested both in terms of further mechanical property optimization and in light of the economics of producing the alloy.

  12. Effect of boron on creep characteristics in 9Cr-1.5Mo alloys

    NASA Astrophysics Data System (ADS)

    Kim, Bumjoon; Yun, Haksu; Lee, Dongbok; Lim, Byeongsoo

    2009-01-01

    For thick-section components such as headers and pipes of the power plants, high creep rupture strength and oxidation resistance are required. It is known that the addition of boron can improve the creep strength and oxidation resistance through the stabilization of M23C6 carbides in the vicinity of prior austenite grain boundaries. In this study, the effect of boron addition with the range of 0.0033~0.0133 wt% on the creep behavior of 9Cr-1.5Mo steel was investigated. Small punch creep tests were carried out to investigate the effect of boron addition on creep properties. Microstructure observation was performed to analyze the effect of boron addition on creep strength and rupture life. Also, the relationship between the minimum creep rate and the amount of boron addition were analyzed. The addition of boron is beneficial in lowering the steady-state creep rate.

  13. Biomimetic calcium phosphate coating on Ti-7.5Mo alloy for dental application.

    PubMed

    Escada, A L A; Machado, J P B; Schneider, S G; Rezende, M C R Alves; Claro, A P R Alves

    2011-11-01

    Titanium and its alloys have been used as bone-replacement implants due to their excellent corrosion resistance and biocompatibility. However, a titanium coating is a bioinert material and cannot bond chemically to bone tissue. The objective of this work was to evaluate the influence of alkaline treatment and heat treatment on the formation of calcium phosphate layer on the surface of a Ti-7.5Mo alloy after soaking in simulated body fluid (SBF). Thirty six titanium alloy plates were assigned into two groups. For group I, samples were immersed in a 5.0-M NaOH aqueous solution at 80°C for 72 h, washed with distilled water and dried at 40°C for 24 h. For group II, after the alkaline treatment, samples were heat-treated at 600°C for 1 h in an electrical furnace in air. Then, all samples were immersed in SBF for 7 or 14 days to allow the formation of a calcium phosphate coating on the surface. The surfaces were characterized using SEM, EDS, AFM and contact angle measurements. PMID:21909642

  14. Structural and Dielectric Studies on Pb(Mg0.5Mo0.5)O3 Compound

    NASA Astrophysics Data System (ADS)

    Barbur, I.; Ardelean, I.; Borodi, G.; Ciomos, D.

    Structural and dielectric measurements were performed on Pb(Mg0.5Mo0.5)O3 (PMM). Polycrystalline samples of PMM were synthesized by solid-state reaction technique at normal pressure. The X-ray measurements indicate formation of single-phase perovskite structure with absence of Mg and Mo ions ordering. The temperature dependence of the relative dielectric constant suggests that PMM undergoes a phase transition (FE or AFE) at 63°C.

  15. Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and 5 mo of age

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effects of prenatal iron supplementation on maternal postpartum iron status and early infant iron homeostasis remain largely unknown. We examined iron absorption and growth in exclusively breastfed infants in relation to fetal iron exposure and iron status during early infancy. Longitudinal, paired ...

  16. Impact toughness of a gradient hardened layer of Cr5Mo1V steel treated by laser shock peening

    NASA Astrophysics Data System (ADS)

    Xia, Weiguang; Li, Lei; Wei, Yanpeng; Zhao, Aimin; Guo, Yacong; Huang, Chenguang; Yin, Hongxiang; Zhang, Lingchen

    2015-09-01

    Laser shock peening (LSP) is a widely used surface treatment technique that can effectively improve the fatigue life and impact toughness of metal parts. Cr5Mo1V steel exhibits a gradient hardened layer after a LSP process. A new method is proposed to estimate the impact toughness that considers the changing mechanical properties in the gradient hardened layer. Assuming a linearly gradient distribution of impact toughness, the parameters controlling the impact toughness of the gradient hardened layer were given. The influences of laser power densities and the number of laser shots on the impact toughness were investigated. The impact toughness of the laser peened layer improves compared with an untreated specimen, and the impact toughness increases with the laser power densities and decreases with the number of laser shots. Through the fracture morphology analysis by a scanning electron microscope, we established that the Cr5Mo1V steel was fractured by the cleavage fracture mechanism combined with a few dimples. The increase in the impact toughness of the material after LSP is observed because of the decreased dimension and increased fraction of the cleavage fracture in the gradient hardened layer.

  17. Impact toughness of a gradient hardened layer of Cr5Mo1V steel treated by laser shock peening

    NASA Astrophysics Data System (ADS)

    Xia, Weiguang; Li, Lei; Wei, Yanpeng; Zhao, Aimin; Guo, Yacong; Huang, Chenguang; Yin, Hongxiang; Zhang, Lingchen

    2016-04-01

    Laser shock peening (LSP) is a widely used surface treatment technique that can effectively improve the fatigue life and impact toughness of metal parts. Cr5Mo1V steel exhibits a gradient hardened layer after a LSP process. A new method is proposed to estimate the impact toughness that considers the changing mechanical properties in the gradient hardened layer. Assuming a linearly gradient distribution of impact toughness, the parameters controlling the impact toughness of the gradient hardened layer were given. The influences of laser power densities and the number of laser shots on the impact toughness were investigated. The impact toughness of the laser peened layer improves compared with an untreated specimen, and the impact toughness increases with the laser power densities and decreases with the number of laser shots. Through the fracture morphology analysis by a scanning electron microscope, we established that the Cr5Mo1V steel was fractured by the cleavage fracture mechanism combined with a few dimples. The increase in the impact toughness of the material after LSP is observed because of the decreased dimension and increased fraction of the cleavage fracture in the gradient hardened layer.

  18. The Flow Behavior and Microstructural Evolution of Ti-5Al-5Mo-5V-3Cr during Subtransus Isothermal Forging

    NASA Astrophysics Data System (ADS)

    Jones, N. G.; Dashwood, R. J.; Dye, D.; Jackson, M.

    2009-08-01

    High-strength metastable β alloys, for example, Ti-5Al-5Mo-5V-3Cr, have replaced steel as the material of choice for large components, such as the main truck beam on the latest generation of airframes. The production of these components is carried out by hot near-net-shape forging, during which process variable control is essential to achieve the desired microstructural condition and subsequent mechanical properties. The flow behavior and microstructural evolution during subtransus isothermal forging of Ti-5Al-5Mo-5V-3Cr has been investigated for two different starting microstructures and analysis has incorporated previously published results. The flow behavior, irrespective of initial microstructural condition, is found to be very similar at strains ≥0.35. It is thought that this is due to a common microstructural state being reached, where dynamic recovery of the β phase is the dominating deformation mechanism. At strains <0.35, the flow behavior is believed to be dominated by the morphology and volume fraction of the α phase. Small globular α particles are thought to have little effect on the flow behavior, while the observed flow softening is directly linked to the fragmentation of acicular α precipitates.

  19. Development of Fe-13%Ni-1.5%Mo Alloy for Ferromagnetic Field Winding Support Shaft of Superconducting Generator

    NASA Astrophysics Data System (ADS)

    Mori, Takanobu; Sato, Hiroyuki; Takahashi, Ryukichi

    Fe-13%Ni-Mo alloy is investigated in order to develop ferromagnetic field winding support shaft of superconducting generator. Solidification test and solidification simulation show that reducing Mo content of the alloy to 1.5% and selecting 1050mm-diameter electroslag remelting process is necessary to avoid harmful macro segregation in the ingot. A trial forging of Fe-13%Ni-1.5%Mo alloy having identical cross section of ferromagnetic field winding support shaft of 200MW machine is manufactured from 1050mm-diameter ingot. A series of test proves that it has no harmful macro segregation and has appropriate properties, that is, stable fracture toughness down to 4K, ferromagnetic property with high flux density, good machinability and weldability. An example of electrical design of 200MW machine shows that the ferromagnetic field winding support shaft can improve output density, efficiency and stability of electrical power system as compared to conventional nonmagnetic one.

  20. The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells.

    PubMed

    Ramalingam, Mahesh; Kim, Sung-Jin

    2016-04-01

    Parkinson's disease (PD) is a common chronic neurodegenerative disorder associated with aging that primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SN). Retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells (SH-SY5Y+RA) have been broadly utilized in studies of mechanisms of the pathogenesis underlying 1-Methyl-4-phenyl pyridinium (MPP(+) )-induced PD models. Here, we investigated the neuroprotective mechanisms of insulin on MPP(+) -induced neurotoxicity on SH-SY5Y+RA cells. Recent studies suggest that insulin has a protective effect against oxidative stress but not been elucidated for PD. In this study, pretreatment of insulin prevented the cell death in a dose dependent manner and lowered nitric oxide (NO) release, reactive oxygen species (ROS), and calcium ion (Ca(2+) ) influx induced by MPP(+) . Insulin also elevated tyrosine hydroxylase (TH) and insulin signaling pathways in dopaminergic neuron through activating PI3K/Akt/GSK-3 survival pathways which in turn inhibits MPP(+) -induced iNOS and ERK activation, and Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on MPP(+) -neurotoxicity in SH-SY5Y+RA cells. J. Cell. Biochem. 117: 917-926, 2016. © 2015 Wiley Periodicals, Inc. PMID:26364587

  1. Creep damage of weldments in 1Cr-0.5Mo steels during long term service at elevated temperature

    SciTech Connect

    Lee, Y.J.; Muddle, B.C.

    1995-08-01

    The cracking of 1Cr-0.5Mo steel stub welds from the Electricity Commission of New South Wales (E.C.N.S.W.) 3rd stage superheater outlet header occurs almost exclusively within the heat affected zone (HAZ). The cracking is intergranular and follows prior austenite grain boundaries. There is extensive cavitation along prior austenite grain boundaries adjacent to and ahead of these cracks. There is an enhanced concentration of MnS inclusions confined almost exclusively to the HAZ of those stub welds from the E.C.N.S.W. header exhibiting cracking. This is attributed to an effective overheating of the HAZ during weld formation, leading to dissolution and then re-precipitation of MnS particles at prior austenite grain boundaries during heating and cooling cycles, respectively. Techniques of scanning electron microscopy, and transmission electron microscopy of extraction replicas from both fracture surfaces and polished and etched sections, have been used to identify the presence of a large volume fraction of sub-micron MnS particles at prior austenite grain boundaries in the HAZ of cracked weldments. Coarse carbides have also been identified at these boundaries, the most common carbides being M{sub 7}C{sub 3} and M{sub 3}C.

  2. Synthesis of CeFe10.5Mo1.5 with ThMn12-type structure by melt spinning

    SciTech Connect

    Zhou, C; Tessema, M; Meyer, MS; Pinkerton, FE

    2013-06-01

    Rare earth compounds RFe12_xMx with tetragonal ThMn12-type structure are of great research interest for potential applications as permanent magnets. These materials are known to serve as the precursors for nitriding and hydriding processes which in certain conditions can dramatically increase the Curie temperature, spontaneous magnetization, and affect the magnetic anisotropy. In this paper, we report the phase study of CeFe10.5Mo1.5 samples melt spun at various surface wheel speeds vs between 5 m/s and 60 m/s. The results from quantitative Rietveld analysis indicate that the as-spun ribbons are a mixture of primary CeFe10.5Mo1.5 phase with impurity phases such as Ce2Fe17, Fe-Mo alloy and CeFe2. When the wheel speed vs is below 25 m/s, CeFe10.5Mo1.5 phase accounts for greater than 85 wt% in the as-spun ribbons, while the Fe-Mo alloy is the only detectable impurity phase. Above v(s)=25 m/s, as the wheel speed increases, CeFe10.5Mo1.5 phase decreases monotonically to about 60 wt% at v(s)=6O m/s while the amounts of impurity phases increase. Thermogravimetric measurement indicates that the Curie temperature T-c. corresponding to CeFe10.5Mo1.5 phase is 341 K. As a result, the best performing sample melt spun at v(s),=15 m/s only exhibits an energy product BHmax=0.121 MGOe at room temperature. Although such a number is modest for a permanent magnet, further nitriding is expected to greatly enhance the Curie temperature, and hence the magnetic performance. (C) 2013 Elsevier B.V. All rights reserved.

  3. The effect of chloride ions on the corroded surface layer of 00Cr22Ni5Mo3N duplex stainless steel under cavitation.

    PubMed

    Wan, Tong; Xiao, Ning; Shen, Hanjie; Yong, Xingyue

    2016-11-01

    The effects of Cl(-) on the corroded surface layer of 00Cr22Ni5Mo3N duplex stainless steel under cavitation in chloride solutions were investigated using nanoindentation in conjunction with XRD and XPS. The results demonstrate that Cl(-) had a strong effect on the nano-mechanical properties of the corroded surface layer under cavitation, and there was a threshold Cl(-) concentration. Furthermore, a close relationship between the nano-mechanical properties and the cavitation corrosion resistance of 00Cr22Ni5Mo3N duplex stainless steel was observed. The degradation of the nano-mechanical properties of the corroded surface layer was accelerated by the synergistic effect between cavitation erosion and corrosion. A key factor was the adsorption of Cl(-), which caused a preferential dissolution of the ferrous oxides in the passive film layer on the corroded surface layer. Cavitation further promoted the preferential dissolution of the ferrous oxides in the passive film layer. Simultaneously, cavitation accelerated the erosion of the ferrite in the corroded surface layer, resulting in the degradation of the nano-mechanical properties of the corroded surface layer on 00Cr22Ni5Mo3N duplex stainless steel under cavitation. PMID:27245950

  4. Synthesis, crystal structure and properties of alluaudite-like triple molybdate Na25Cs8Fe5(MoO4)24

    NASA Astrophysics Data System (ADS)

    Savina, Aleksandra A.; Solodovnikov, Sergey F.; Belov, Dmitry A.; Basovich, Olga M.; Solodovnikova, Zoya A.; Pokholok, Konstantin V.; Stefanovich, Sergey Yu.; Lazoryak, Bogdan I.; Khaikina, Elena G.

    2014-12-01

    A new triple molybdate Na25Cs8Fe5(MoO4)24 was synthesized using solid state reactions and studied with X-ray powder diffraction, second harmonic generation (SHG) technique, differential scanning calorimetry, Mössbauer and dielectric impedance spectroscopy. Single crystals of Na25Cs8Fe5(MoO4)24 were obtained and its structure was solved (the space group P1bar, a=12.5814(5), b=13.8989(5), c=28.4386(9) Å, α=90.108(2), β=90.064(2), γ=90.020(2)°, V=4973.0(3) Å3, Z=2, R=0.0440). Characteristic features of the structure are polyhedral layers composed of pairs of edge-shared FeO6 and (Fe, Na)O6 octahedra, which are connected by bridging МоО4 tetrahedra. The layers share common vertices with bridging МоО4 tetrahedra to form an open 3D framework with the cavities occupied by the Cs+ and Na+ cations. The compound undergoes first-order phase transformation at 642 K and above this phase transition, electrical conductivity reaches 10-3-10-2 S cm-1. Thus, Na25Cs8Fe5(MoO4)24 may be considered as a promising compound for developing new materials with high ionic conductivity.

  5. Growth, spectral property and crystal field analysis of Cr3+-doped Na2Mg5(MoO4)6 crystal

    NASA Astrophysics Data System (ADS)

    Zhang, Lizhen; Li, Linyun; Huang, Yisheng; Sun, Shijia; Lin, Zhoubin; Wang, Guofu

    2015-11-01

    This paper reports the growth and spectral properties of Cr3+:Na2Mg5(MoO4)6 crystals. The Na2Mg5(MoO4)6 crystal was grown from a flux of Na2Mo2O7 by the top seeded solution growth method. The absorption cross-sections are 0.692 × 10-19 cm2 at 507 nm and 1.151 × 10-19 cm2 at 736 nm, respectively. The emission cross-section is 1.62 × 10-19 cm2 at 914 nm with FWHM of 192 nm. Based on the absorption and emission spectra, the crystal field strength Dq, the Racah parameters B and C, effective phonon energy ℏω and the Huang-Rhys factor S were calculated. The spectral properties of Cr3+:Na2Mg5(MoO4)6 crystal demonstrate a good potential for tunable laser material.

  6. The cluster compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} containing Mo{sub 14} clusters and the new mono- and bi-capped trioctahedral Mo{sub 15} and Mo{sub 16} clusters: Synthesis, crystal structure, and electrical and magnetic properties

    SciTech Connect

    Gall, Philippe; Guizouarn, Thierry; Gougeon, Patrick

    2015-07-15

    Single crystals of the new quaternary compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} were obtained by solid state reaction. The crystal structure was determined by single-crystal X-ray diffraction. In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} crystallizes in the orthorhombic space group Pbca with unit-cell parameters a=9.4432(14) Å, b=11.4828(12) Å, c=20.299(4) Å and Z=4. Full-matrix least-squares refinement on F{sup 2} using 3807 independent reflections for 219 refinable parameters resulted in R{sub 1}=0.0259 and wR{sub 2}=0.0591. The crystal structure contains in addition to Mo{sub 14} clusters the first examples of mono- and bi-capped trioctahedral Mo{sub 14} i.e. Mo{sub 15} and Mo{sub 16} clusters. The oxygen framework derives from a stacking along the a direction of close-packed layers with sequence (…ABAC…). The Mo–Mo distances range between 2.6938(5) and 2.8420(6) Å and the Mo–O distances between 1.879(5) and 2.250(3) Å, as usually observed in molybdenum oxide clusters. The indium atoms form In{sub 4}{sup 6+} bent chains with In–In distances of 2.6682(5) and 2.6622(8) Å and the Ti atoms are in highly distorted octahedral sites of oxygen atoms with Ti–O distances ranging between 1.865(4) and 2.161(4) Å. Magnetic susceptibility measurements confirm the presence of Ti{sup 4+} cations and the absence of localized moments on the Mo network. Electrical resistivity measurements on a single crystal of In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} show a semimetallic behavior. - Graphical abstract: We present here the synthesis, the crystal structure, and the electrical and magnetic properties of the new compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} in which Mo{sub 14} clusters coexist statistically with mono- and bi-capped trioctahedral Mo{sub 14} that is Mo{sub 15} and Mo{sub 16} clusters. - Highlights: • Single crystals of In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} were obtained by solid state

  7. A new method to effectively and rapidly generate neurons from SH-SY5Y cells.

    PubMed

    Yang, HongNa; Wang, Jing; Sun, JinHua; Liu, XiaoDun; Duan, Wei-Ming; Qu, TingYu

    2016-01-01

    It is well known that neurons differentiated from SH-SY5Y cells can serve as cell models for neuroscience research; i.e., neurotoxicity and tolerance to morphine in vitro. To differentiate SH-SY5Y cells into neurons, RA (retinoic acid) is commonly used to produce the inductive effect. However, the percentage of neuronal cells produced from SH-SY5Y cells is low, either from the use of RA treatment alone or from the combined application of RA and other chemicals. In the current study, we used CM-hNSCs (conditioned medium of human neural stem cells) as the combinational inducer with RA to prompt neuronal differentiation of SH-SY5Y cells. We found that neuronal differentiation was improved and that neurons were greatly increased in the differentiated SH-SY5Y cells using a combined treatment of CM-hNSCs and RA compared to RA treatment alone. The neuronal percentage was higher than 80% (about 88%) on the 3rd day and about 91% on the 7th day examined after a combined treatment with CM-hNSCs and RA. Cell maturation and neurite growth of these neuronal cells were also improved. In addition, the use of CM-hNSCs inhibited the apoptosis of RA-treated SH-SY5Y cells in culture. We are the first to report the use of CM-hNSCs in combination with RA to induce neuronal differentiation of RA-treated SH-SY5Y cells. Our method can rapidly and effectively promote the neuronal production of SH-SY5Y cells in culture conditions. PMID:26497914

  8. Structure of compound Pr{sub 5}Mo{sub 3}O{sub 16+δ} exhibiting mixed electronic—ionic conductivity

    SciTech Connect

    Antipin, A. M. Alekseeva, O. A.; Sorokina, N. I.; Kuskova, A. N.; Artemov, V. V.; Murzin, V. Yu.; Kharitonava, E. P.; Orlova, E. A.; Voronkova, V. I.

    2015-09-15

    The structure of Pr{sub 5}Mo{sub 3}O{sub 16+δ} single crystals is studied by X-ray diffraction, EDXS microanalysis, transmission microscopy, and XANES spectroscopy. It is found that in the structure Pr and Mo cations mutually replace each other, atomic positions of oxygen are split into several additional positions, and structural voids accommodate interstitial oxygen atoms (which make the main contribution to the conductivity). The disorder of the oxygen sublattice is responsible for the continuity of the framework of the ways of migration of oxygen ions.

  9. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  10. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  11. Characterization of the structure, thermal stability and wettability of the TiO2 nanotubes growth on the Ti-7.5Mo alloy surface

    NASA Astrophysics Data System (ADS)

    Chaves, J. M.; Escada, A. L. A.; Rodrigues, A. D.; Alves Claro, A. P. R.

    2016-05-01

    In this study, the Ti-7.5Mo experimental alloy for biomedical applications was processed showing orthorhombic (α″) martensite phase and low elastic modulus (54 GPa). The surface treatment permitted the growth of ordered TiO2 nanotubes via anodization process. The heat treatment during in situ Raman measurement revealed that the TiO2 nanotubes were transformed of the amorphous state for crystalline (anatase phase) around 400 °C. Annealing of the nanotubes was evaluated by XRD, SEM and Raman spectroscopy. Results showed a high stability of the nanostructure, since only for temperatures above of 500 °C, at which the phase rutile appears, the nanostructure tends to vanish. It was observed in Raman analysis an increasing of the average size of the crystallite of the anatase phase with annealing temperature ranging from 6.5 nm up to 13 nm, besides of the precipitation of the layer rutile in the interface nanotubes-substrate. It is believed that the contact between anatase crystallites or layer rutile of the interface lead to growth of the rutile phase, causing coalescence and subsequent collapse of the tubular nanostructure. The wettability, as well as, surface energy was dependent of the crystalline structure and morphology, becoming more hydrophilic in the anatase phase when as compared with amorphous and rutile phase. The typical features of the surface together excellent bulk properties (low elastic modulus) of the Ti-7.5Mo alloy can provide a guideline for future biomedical applications.

  12. Fretting wear behavior of laser-nitrided Ti-5Al-5Mo-5V-1Cr-1Fe alloy fabricated by laser melting deposition

    NASA Astrophysics Data System (ADS)

    Liu, L.; Shangguan, Y. J.; Tang, H. B.; Wang, H. M.

    2014-09-01

    Fretting wear behavior of laser-nitrided titanium alloy (Ti-5Al-5Mo-5V-1Cr-1Fe) fabricated by laser melting deposition (LMD) has been investigated to explore surface engineering for protection against wear damage of laser melting deposited titanium alloy. The morphology and volume of the wear scars of unmodified and laser-nitrided LMD Ti-5Al-5Mo-5V-1Cr-1Fe tested at different frequencies, 10 and 50 Hz, were studied using non-contact three-dimensional surface profilometer and scanning electron microscope. Friction coefficients measured at different frequencies or loading forces were compared for unmodified and laser-nitrided LMD specimens. Experimental results show that laser-nitrided LMD specimens have shown fretting resistance superior to unmodified LMD specimens due to the presence of hard TiN dendrites in the laser-nitrided layer. W-shaped wear scar caused by local rotation of fretting ball at the two ends of the scar was observed. Given a constant loading force of 50 N, unmodified and laser-nitrided LMD specimens exhibited similar friction coefficients and their friction coefficients increased with test frequency. The friction coefficients of both specimens increased with the reduction of normal load, which corresponds to the trend in Hertzian contact model.

  13. Catalytic performance of V2O5-MoO3/γ-Al2O3 catalysts for partial oxidation of n-hexane1

    NASA Astrophysics Data System (ADS)

    Mahmoudian, R.; Khodadadi, Z.; Mahdavi, Vahid; Salehi, Mohammed

    2016-01-01

    In the current study, a series of V2O5-MoO3 catalyst supported on γ-Al2O3 with various V2O5 and MoO3 loadings was prepared by wet impregnation technique. The characterization of prepared catalysts includes BET surface area, powder X-ray diffraction (XRD), and oxygen chemisorptions. The partial oxidation of n-hexane by air over V2O5-MoO3/γ-Al2O3 catalysts was carried out under flow condition in a fixed bed glass reactor. The effect of V2O5 loading, temperature, MoO3 loading, and n-hexane LHSV on the n-hexane conversion and the product selectivity were investigated. The partial oxygenated products of n-hexane oxidation were ethanol, acetic anhydride, acetic acid, and acetaldehyde. The 10% V2O5-1%MoO3/γ-Al2O3 was found in most active and selective catalyst during partial oxidation of n-hexane. The results indicated that by increasing the temperature, the n-hexane conversion increases as well, although the selectivity of the products passes through a maximum by increasing the temperature.

  14. Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y

    PubMed Central

    Jones, Simon A.; Bialer, Martin; Parini, Rossella; Martin, Ken; Wang, Hui; Yang, Ke; Shaywitz, Adam J.; Harmatz, Paul

    2015-01-01

    Background: Previous studies have shown that elosulfase alfa has a favorable efficacy/safety profile in Morquio A patients aged5 y. This study evaluated safety and impact on urine keratan sulfate (uKS) levels and growth velocity in younger patients. Methods: Fifteen Morquio A patients aged <5 y received elosulfase alfa 2.0 mg/kg/week for 52 wk during the primary treatment phase of a phase II, open-label, multinational study. Primary endpoint was safety and tolerability; secondary endpoints were change in uKS and growth velocity over 52 wk. Results: All 15 patients completed the primary treatment phase. Six of 743 infusions (0.8%) administered led to adverse events (AEs) requiring infusion interruption and medical intervention. Eleven patients (73.3%) had ≥1 study drug-related AE, mostly infusion-associated reactions. Mean z-score growth rate per year numerically improved from −0.6 at baseline to −0.4 at week 52. Comparison to untreated subjects of similar age in the Morquio A Clinical Assessment Program study showed a smaller decrease in height z-scores for treated than for untreated patients. Mean percent change from baseline in uKS was −30.2% at 2 wk and −43.5% at 52 wk. Conclusion: Early intervention with elosulfase alfa is well-tolerated and produces a decrease in uKS and a trend toward improvement in growth. PMID:26331768

  15. Propolis Inhibits Neurite Outgrowth in Differentiating SH-SY5Y Human Neuroblastoma Cells.

    PubMed

    Kim, Han Bit; Yoo, Byung Sun

    2016-07-01

    Propolis is a multicomponent, active, complex resinous substance collected by honeybees from a variety of plant sources. We have studied the effect of propolis on neurite outgrowth of SH-SY5Y human neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Propolis, at a concentration of 3 μg/mL, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells treated with propolis (0.3~3 μg/mL) for 48 hr was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 0.3 to 3 μg/mL propolis resulted in decreased level of transglutaminase and 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The results indicate that propolis is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells. PMID:27437091

  16. Propolis Inhibits Neurite Outgrowth in Differentiating SH-SY5Y Human Neuroblastoma Cells

    PubMed Central

    Kim, Han Bit; Yoo, Byung Sun

    2016-01-01

    Propolis is a multicomponent, active, complex resinous substance collected by honeybees from a variety of plant sources. We have studied the effect of propolis on neurite outgrowth of SH-SY5Y human neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Propolis, at a concentration of 3 μg/mL, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells treated with propolis (0.3~3 μg/mL) for 48 hr was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 0.3 to 3 μg/mL propolis resulted in decreased level of transglutaminase and 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The results indicate that propolis is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells. PMID:27437091

  17. Characterization of Differentiated SH-SY5Y as Neuronal Screening Model Reveals Increased Oxidative Vulnerability

    PubMed Central

    Forster, J. I.; Köglsberger, S.; Trefois, C.; Boyd, O.; Baumuratov, A. S.; Buck, L.; Balling, R.; Antony, P. M. A.

    2016-01-01

    The immortalized and proliferative cell line SH-SY5Y is one of the most commonly used cell lines in neuroscience and neuroblastoma research. However, undifferentiated SH-SY5Y cells share few properties with mature neurons. In this study, we present an optimized neuronal differentiation protocol for SH-SY5Y that requires only two work steps and 6 days. After differentiation, the cells present increased levels of ATP and plasma membrane activity but reduced expression of energetic stress response genes. Differentiation results in reduced mitochondrial membrane potential and decreased robustness toward perturbations with 6-hydroxydopamine. We are convinced that the presented differentiation method will leverage genetic and chemical high-throughput screening projects targeting pathways that are involved in the selective vulnerability of neurons with high energetic stress levels. PMID:26738520

  18. Microstructure and property modifications of an AISI H13 (4Cr5MoSiV) steel induced by pulsed electron beam treatment

    SciTech Connect

    Zhang Kemin; Zou Jianxin; Grosdidier, Thierry; Dong Chuang

    2010-11-15

    In the present work, surface modifications generated by the low energy high current pulsed electron beam (LEHCPEB) treatments have been investigated on an AISI H13 (4Cr5MoSiV) steel. From the observations of scanning electron microscopy, x-ray diffraction, and electron back scattering diffraction determinations, it could be established that the final structure in the melted layer is a mixture of ultrafine {delta} phase, martensite, and residual austenite. The formation of the heterogeneous microstructures on the surface layer is related to the very rapid heating, melting, solidification, and cooling induced by the LEHCPEB irradiation. After the LEHCPEB treatment, the wear resistance of the steel effectively improved. This can be mainly attributed to the higher hardness of the ultrafine structures formed on the top surface and the hardened subsurface layers after the treatment.

  19. Comparison of Heat Treatments on the Toughness of 1.7Ni-1.5Cu-0.5Mo Pre-alloyed P/M Steels

    NASA Astrophysics Data System (ADS)

    Güral, Ahmet; Türkan, Mustafa

    2015-05-01

    Effects of quenching plus tempering and intercritical annealing plus quenching heat treatments on the impact toughness properties of 1.7Ni-1.5Cu-0.5Mo pre-alloyed powder metallurgy steels with 0.2 (in mass%) graphite were investigated. Specimens were prepared by pressing at 670 MPa and sintering at 1250 °C. Different heat treatments, namely quenching and tempering, directly intercritically annealing and fully austenization plus intercritically annealing were carried out on the sintered specimens. The results showed that the impact toughness decreased with increasing intercritical annealing temperature in ferrite plus martensite dual phase powder metallurgy steels and with increasing tempering temperature in the quenched plus tempered specimens. Besides, impact toughness of fully austenizated plus intercritically annealed specimens was higher than those of quenched plus tempered and directly intercritically annealed specimens at the same hardness levels.

  20. Flowerlike CeO2 microspheres coated with Sr2Fe1.5Mo0.5Ox nanoparticles for an advanced fuel cell

    NASA Astrophysics Data System (ADS)

    Liu, Yanyan; Tang, Yongfu; Ma, Zhaohui; Singh, Manish; He, Yunjuan; Dong, Wenjing; Sun, Chunwen; Zhu, Bin

    2015-07-01

    Flowerlike CeO2 coated with Sr2Fe1.5Mo0.5Ox (Sr-Fe-Mo-oxide) nanoparticles exhibits enhanced conductivity at low temperatures (300-600 oC), e.g. 0.12 S cm-1 at 600 oC, this is comparable to pure ceria (0.1 S cm-1 at 800 oC). Advanced single layer fuel cell was constructed using the flowerlike CeO2/Sr-Fe-Mo-oxide layer attached to a Ni-foam layer coated with the conducting transition metal oxide. Such fuel cell has yielded a peak power density of 802 mWcm-2 at 550 oC. The mechanism of enhanced conductivity and cell performance were analyzed. These results provide a promising strategy for developing advanced low-temperature SOFCs.

  1. Flowerlike CeO2 microspheres coated with Sr2Fe1.5Mo0.5Ox nanoparticles for an advanced fuel cell

    PubMed Central

    Liu, Yanyan; Tang, Yongfu; Ma, Zhaohui; Singh, Manish; He, Yunjuan; Dong, Wenjing; Sun, Chunwen; Zhu, Bin

    2015-01-01

    Flowerlike CeO2 coated with Sr2Fe1.5Mo0.5Ox (Sr-Fe-Mo-oxide) nanoparticles exhibits enhanced conductivity at low temperatures (300–600 oC), e.g. 0.12 S cm−1 at 600 oC, this is comparable to pure ceria (0.1 S cm−1 at 800 oC). Advanced single layer fuel cell was constructed using the flowerlike CeO2/Sr-Fe-Mo-oxide layer attached to a Ni-foam layer coated with the conducting transition metal oxide. Such fuel cell has yielded a peak power density of 802 mWcm−2 at 550 oC. The mechanism of enhanced conductivity and cell performance were analyzed. These results provide a promising strategy for developing advanced low-temperature SOFCs. PMID:26154917

  2. Effect of a 5-mo nutritional intervention on nutritional status and quality of life for patient with 3-hydroxyisobutyryl-coenzyme A hydrolase deficiency: A case report.

    PubMed

    Li, Chun-Wei; Yu, Kang; Xu, Yan; Sun, Xia-Yuan; Li, Rong-Rong; Wang, Fang

    2015-01-01

    3-Hydroxy-isobutyryl-coenzyme A (CoA) hydrolase (HBICH) deficiency is a rare cerebral organic aciduria caused by disturbance of valine catabolism that leads to the accumulation of toxic metabolites, methacrylyl-CoA. The major feature exhibited by a patient with HBICH deficiency includes multiple congenital malformations and abnormal neurologic findings. However, the pathophysiology of this disease remains unknown. The major treatment for HBICH deficiency involves a low-protein diet, especially restricting valine, supplemented with micronutrients and carnitine. To our knowledge, only four patients with HBICH deficiency have been reported. These patients were boys and presented with different clinical, biochemical, and genetic features than our patient. In this report, we described what was to our knowledge the first genetically confirmed girl with HBICH deficiency in China. A 5-mo nutritional intervention was given to the patient by a nutritional support team. On this regimen, the patient's symptoms were alleviated and her quality of life was improved. PMID:26001807

  3. An investigation of the fatigue and fracture behavior of a Nb-12Al-44Ti-1.5Mo intermetallic alloy

    SciTech Connect

    Soboyejo, W.O.; Dipasquale, J.; Ye, F.; Mercer, C.; Srivatsan, T.S.; Konitzer, D.G.

    1999-04-01

    This article presents the results of a study of the fatigue and fracture behavior of a damage-tolerant Nb-12Al-44Ti-1.5Mo alloy. This partially ordered B2 + orthorhombic intermetallic alloy is shown to have attractive combinations of room-temperature ductility (11 to 14 pct), fracture toughness (60 to 92 MPa{radical}m), and comparable fatigue crack growth resistance to IN718, Ti-6Al-4V, and pure Nb at room temperature. The studies show that tensile deformation in the Nb-12Al-44Ti-1.5Mo alloy involves localized plastic deformation (microplasticity via slip-band formation) which initiates at stress levels that are significantly below the uniaxial yield stress ({approximately}9.6 pct of the 0.2 pct offset yield strength (YS)). The onset of bulk yielding is shown to correspond to the spread of microplasticity completely across the gage sections of the tensile specimen. Fatigue crack initiation is also postulated to occur by the accumulation of microplasticity (coarsening of slip bands). Subsequent fatigue crack growth then occurs by the unzipping of cracks along slip bands that form ahead of the dominant crack tip. The proposed mechanism of fatigue crack growth is analogous to the unzipping crack growth mechanism that was suggested originally by Neumann for crack growth in single-crystal copper. Slower near-threshold fatigue crack growth rates at 750 C are attributed to the shielding effects of oxide-induced crack closure. The fatigue and fracture behavior are also compared to those of pure Nb and emerging high-temperature niobium-based intermetallics.

  4. Phenotypic Characterization of Retinoic Acid Differentiated SH-SY5Y Cells by Transcriptional Profiling

    PubMed Central

    Korecka, Joanna A.; van Kesteren, Ronald E.; Blaas, Eva; Spitzer, Sonia O.; Kamstra, Jorke H.; Smit, August B.; Swaab, Dick F.; Verhaagen, Joost; Bossers, Koen

    2013-01-01

    Multiple genetic and environmental factors play a role in the development and progression of Parkinson’s disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD. PMID:23724009

  5. Shuyusan-containing serum protects SH-SY5Y cells against corticosterone-induced impairment

    PubMed Central

    Chen, Liping; Sun, Zhigao; Wang, Fawei; Xu, Chengyong; Geng, Miao; Chen, Hongyan; Duan, Dongmei

    2013-01-01

    The Chinese herb Shuyusan, whose main constituent is jasminoidin, has been shown to protect SH-SY5Y cells against corticosterone-induced damage. SH-SY5Y cells injured by 400 μmol/L corticosterone were treated with 5 and 30 μg/mL Shuyusan-containing serum. Results revealed that Shuyusan-containing serum elevated the survival rate of SH-SY5Y cells, reduced Bax expression, increased Bcl-2 expression, markedly elevated brain-derived neurotrophic factor mRNA expression, and blocked cell apoptosis. Moreover, the effect of high-dose (30 μg/mL) Shuyusan-containing serum was more remarkable. Therefore, Shuyusan-containing serum appears to protect SH-SY5Y cells against corticosterone-induced impairment by adjusting the expression of apoptosis-associated proteins and brain-derived neurotrophic factor. Moreover, high-dose Shuyusan-containing serum has a protective effect on high-dose corticosterone-induced impairment. PMID:25206514

  6. Comparative proteomic analysis of human SH-SY5Y neuroblastoma cells under simulated microgravity.

    PubMed

    Zhang, Yongqian; Wang, Hongbin; Lai, Chengjun; Wang, Lu; Deng, Yulin

    2013-02-01

    Microgravity is one of the most important features in spaceflight. Previous evidence has shown that neurophysiological impairment signs occurred under microgravity. The present study was undertaken to explore the change in protein abundance in human SH-SY5Y neuroblastoma cells that were grown in a microgravity environment. The comparative proteomic method based on the (18)O labeling technique was applied to investigate the up-regulated proteins and down-regulated proteins in SH-SY5Y under simulated microgravity. Twenty-two differentially abundant proteins were quantified in human SH-SY5Y neuroblastoma cells. The cell microfilament network was disrupted under simulated microgravity, which was determined by the immunocytochemistry. The concentration of reactive oxygen species, malondialdehyde, and free Ca2+ ion significantly increased, and the level of ATP significantly decreased under simulated microgravity. However, there was no obvious cell apoptosis observed under simulated microgravity. These results provide new molecular evidence for the change in protein abundance in SH-SY5Y cells under simulated microgravity, which might unfold biological mechanisms and the development of effective countermeasures to deal with microgravity-related neurological problems. We believe that the state-of-the-art proteomic assay may be a means by which aerospace scientists will begin to understand the underlying mechanisms of space life activities at the protein level. PMID:23421552

  7. Handwriting, Visuomotor Integration, and Neurological Condition at School Age

    ERIC Educational Resources Information Center

    Van Hoorn, Jessika F.; Maathuis, Carel G. B.; Peters, Lieke H. J.; Hadders-Algra, Mijna

    2010-01-01

    Aim: The study investigated the relationships between handwriting, visuomotor integration, and neurological condition. We paid particular attention to the presence of minor neurological dysfunction (MND). Method : Participants were 200 children (131 males, 69 females; age range 8-13y) of whom 118 received mainstream education (mean age 10y 5mo, SD…

  8. Effect of Amaranthus on Advanced Glycation End-Products Induced Cytotoxicity and Proinflammatory Cytokine Gene Expression in SH-SY5Y Cells.

    PubMed

    Amornrit, Warisa; Santiyanont, Rachana

    2015-01-01

    Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Advanced glycation end-products (AGEs) cause cell toxicity in the human neuronal cell line, SH-SY5Y, through an increase in oxidative stress, as shown by reducing cell viability and increasing cell toxicity in a dose-dependent manner. We found that preincubation of SH-SY5Y cells with either petroleum ether, dichloromethane or methanol extracts of A. lividus and A. tricolor dose-dependently attenuated the neuron toxicity caused by AGEs treatment. Moreover, the results showed that A. lividus and A. tricolor extracts significantly downregulated the gene expression of the pro-inflammatory cytokines, TNF-α, IL-1 and IL-6 genes in AGEs-induced cells. We concluded that A. lividus and A. tricolor extracts not only have a neuroprotective effect against AGEs toxicity, but also have anti-inflammatory activity by reducing pro-inflammatory cytokine gene expression. This suggests that Amaranthus may be useful for treating chronic inflammation associated with neurodegenerative disorders. PMID:26393562

  9. SH-SY5Y neuroblastoma cells: a model system for studying biosynthesis of NAAG.

    PubMed

    Arun, Peethambaran; Madhavarao, Chikkathur N; Hershfield, Jeremy R; Moffett, John R; Namboodiri, M A Aryan

    2004-05-19

    N-Acetylaspartylglutamate (NAAG) is a neuropeptide that is thought to modulate neurotransmitter release through pre-synaptic mGluR3 receptors. Despite years of research into NAAG biochemistry, almost nothing is known about NAAG biosynthesis. To date, NAAG biosynthesis has only been demonstrated conclusively in explanted animal neural tissues, including frog retina, rat dorsal root ganglia and crayfish nerve cord, but not in human cells or tissues. We show here that a human neuroblastoma cell line, SH-SY5Y, provides a good model system for the study of NAAG biosynthesis. Radiolabled NAAG synthesis occurred using both L-[3H]glutamic acid and L-[3H]glutamine as precursors, with glutamine being the preferred substrate. Differentiation of SH-SY5Y cells with retinoic acid resulted in decreased radiolabel incorporation into NAAG, whereas differentiation with nerve growth factor did not affect radiolabel incorporation. PMID:15129167

  10. Preparation and structural study from neutron diffraction data of Pr{sub 5}Mo{sub 3}O{sub 16}

    SciTech Connect

    Martinez-Lope, M.J.; Alonso, J.A.; Sheptyakov, D.; Pomjakushin, V.

    2010-12-15

    The title compound has been prepared as polycrystalline powder by thermal treatments of mixtures of Pr{sub 6}O{sub 11} and MoO{sub 2} in air. In the literature, an oxide with a composition Pr{sub 2}MoO{sub 6} has been formerly described to present interesting catalytic properties, but its true stoichiometry and crystal structure are reported here for the first time. It is cubic, isostructural with CdTm{sub 4}Mo{sub 3}O{sub 16} (space group Pn-3n, Z=8), with a=11.0897(1) A. The structure contains MoO{sub 4} tetrahedral units, with Mo-O distances of 1.788(2) A, fully long-range ordered with PrO{sub 8} polyhedra; in fact it can be considered as a superstructure of fluorite (M{sub 8}O{sub 16}), containing 32 MO{sub 2} fluorite formulae per unit cell, with a lattice parameter related to that of cubic fluorite (a{sub f}=5.5 A) as a{approx}2a{sub f}. A bond valence study indicates that Mo exhibits a mixed oxidation state between 5+ and 6+ (perhaps accounting for the excellent catalytic properties). One kind of Pr atoms is trivalent whereas the second presents a mixed Pr{sup 3+}-Pr{sup 4+} oxidation state. The similarity of the XRD pattern with that published for Ce{sub 2}MoO{sub 6} suggests that this compound also belongs to the same structural type, with an actual stoichiometry Ce{sub 5}Mo{sub 3}O{sub 16}. -- Graphical Abstract: Formerly formulated as Pr{sub 2}MoO{sub 6}, the title compound is a cubic superstructure of fluorite (a=11.0897(1) A, space group Pn-3n) due to the long-range ordering of PrO{sub 8} scalenohedra and MoO{sub 4} tetrahedral units, showing noticeable shifts of the oxygen positions in order to provide a tetrahedral coordination for Mo ions. A mixed valence Mo{sup 5+}-Mo{sup 6+} is identified, which could account for the excellent catalytic properties of this material. Display Omitted

  11. Solving Fermat-type equations x^5+y^5=dz^p

    NASA Astrophysics Data System (ADS)

    Billerey, Nicolas; Dieulefait, Luis V.

    2010-01-01

    In this paper, we are interested in solving the Fermat-type equations x^5+y^5=dz^p , where d is a positive integer and p a prime number ≥ 7 . We describe a new method based on modularity theorems which allows us to improve all earlier results for this equation. We finally discuss the present limits of the method by looking at the case d=3 .

  12. Chlorpyrifos and cypermethrin induce apoptosis in human neuroblastoma cell line SH-SY5Y.

    PubMed

    Raszewski, Grzegorz; Lemieszek, Marta Kinga; Łukawski, Krzysztof; Juszczak, Małgorzata; Rzeski, Wojciech

    2015-02-01

    Our previous in vivo studies showed that chlorpyrifos (CPF) and cypermethrin (CM) in a mixture dermally administered, strongly inhibited cholinesterase activity in plasma and the brain and were very toxic to the rat central nervous system. In this work, the mechanisms of neurotoxicity have not been elucidated. We used human undifferentiated SH-SY5Y cells to study mechanisms of pesticide-induced neuronal cell death. It was found that chlorpyrifos (CPF) and its mixture with cypermethrin (CPF+CM) induced cell death of SH-SY5Y cells in a dose- and time-dependent manner, as shown by MTT assays. Pesticide-induced SH-SY5Y cell death was characterized by concentration-dependent down-regulation of Bcl-2 and Bcl-xL as well as an increase in the caspase 3 activation. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal effect of pesticide-induced toxicity indicating that the major caspase pathways are not integral to CPF- and CPF+CM-induced cell death. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 and mecamylamine failed to attenuate pesticides effect. Atropine exhibited minimal ability to reverse toxicity. Finally, it was shown that inhibition of TNF-α by pomalidomide attenuated CPF-/CPF+CM-induced apoptosis. Overall, our data suggest that FAS/TNF signalling pathways may participate in CPF and CPF+CM toxicity. PMID:24975276

  13. Weightlessness influences the cytoskeleton and ROS level in SH-SY5Y neuroblastoma cells

    NASA Astrophysics Data System (ADS)

    Bo, Wang; Lina, Qu; Yingxian, Li; Qi, Li; Lei, Bi; Yinghui, Li

    During Spaceflight the nerve system of astronauts was obviously influenced To investigate how gravity effects nerve system the SH-SY5Y neuroblastoma cells were taken as research object By utilizing clinostat and parabolic flight for the model of gravity changing the level of reactive oxygen species was assayed in different time under simulated microgravity the cytomorphology and cytoskeleton of SH-SY5Y neuroblastoma cells were also observed after parabolic flight and clinostat by the conventional and the confocal laser scanning microscope The data showed that ROS level was enhanced and the cytoskeleton was damaged which microfilaments and microtubules were highly disorganized the cell shape was deteriorated under simulated microgravity indicating the relativity between the ROS level fluctuating and cytoskeleton changing It illuminates signal transduction disturbed by oxidative stress also regulates the cytoskeleton changing in SH-SY5Y cells The results suggest the cytoskeleton which is the receptor for sensing gravity was also regulated by cellular redox state which clues on the complexity of cell for self-adjusting to gravity changing

  14. Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells

    SciTech Connect

    Chen Yan; Yu Min; Jones, Dean P.; Greenamyre, J. Timothy; Cai Jiyang . E-mail: jiyang.cai@vanderbilt.edu

    2006-10-15

    Mitochondrial oxidative stress plays important roles in aging and age-related degenerative disorders. The newly identified mitochondrial thioredoxin (mtTrx; Trx2) is a key component of the mitochondrial antioxidant system which is responsible for the clearance of reactive intermediates and repairs proteins with oxidative damage. Here, we show that in cultured SH-SY5Y human neuroblastoma 1cells, overexpression of mtTrx inhibited apoptosis and loss of mitochondrial membrane potential induced by a chemical oxidant, tert-butylhydroperoxide (tBH). The effects of calcium ionophore (Br-A23187) were not affected by mtTrx, suggesting the protection was specific against oxidative injury. The mitochondrial glutathione pool was oxidized by tBH, and this oxidation was not inhibited by increased mtTrx. Consequently, the antioxidant function of mtTrx is not redundant, but rather in addition, to that of GSH. Mutations of Cys90 and Cys93 to serines rendered mtTrx ineffective in protection against tBH-induced cytoxicity. These data indicate that mtTrx controls the mitochondrial redox status independently of GSH and is a key component of the defensive mechanism against oxidative stress in cultured neuronal cells.

  15. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    SciTech Connect

    Park, Jae Hyeon; Lee, Jeong Eun; Shin, In Chul; Koh, Hyun Chul

    2013-04-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  16. The Effect of Colored Titanium Oxides on the Color Change on the Surface of Ti-5Al-5Mo-5V-1Cr-1Fe Alloy

    NASA Astrophysics Data System (ADS)

    Peng, Wenwen; Zeng, Weidong; Zhang, Yaowu; Shi, Chunling; Quan, Biao; Wu, Jianding

    2013-09-01

    In the present investigation, a color change on the surface of Ti-5Al-5Mo-5V-1Cr-1Fe alloy was studied through thermal oxidation experiments in the temperature range of 100-1000 °C with an interval of 50 °C. The phase composition and morphology of oxide layer were characterized by x-ray diffraction and light optical microscopy, respectively. The result shows that the achieved colors after thermal oxidation followed a chromatic scale which went from silver white to light yellow to golden yellow to blue and then to light green and brownish black. The color change on the alloy mainly resulted from the different colored titanium oxides in the oxide layer. The silver white, yellow, and blue on the alloy with the oxidation temperature below 600 °C were the results of TiO2 white tint, TiO golden tint, and Ti2O3 blue color, respectively. The light green was the mixed color of TiO golden tint and Ti2O3 blue color in the oxidation temperature range of 600-700 °C. However, at the oxidation temperatures exceeding 750 °C, the color turned to be brownish black. It might be associated with the thick, porous, and multilayered oxide layer. Consequently, it can be suggested that the illustration of the color change is vitally necessary for assessing the quality of the final workpieces according to the color change on titanium alloys.

  17. Polysulfides protect SH-SY5Y cells from methylglyoxal-induced toxicity by suppressing protein carbonylation: A possible physiological scavenger for carbonyl stress in the brain.

    PubMed

    Koike, Shin; Kayama, Tasuku; Yamamoto, Shigeyoshi; Komine, Daisuke; Tanaka, Ryo; Nishimoto, Shoichi; Suzuki, Toshihiro; Kishida, Atsushi; Ogasawara, Yuki

    2016-07-01

    The formation of advanced glycation end products (AGEs) is associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease and schizophrenia. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is known to be a major precursor for AGEs in modified proteins. Thus, a scavenger of MG might provide beneficial effects by suppressing the accumulation of AGEs and the occurrence of diseases induced by carbonyl stress. Meanwhile, polysulfides, one of the typical bound sulfur species, are oxidized forms of hydrogen sulfide (H2S) and may play a variety of roles in the brain. Herein, we assessed the scavenging ability of polysulfides against neuronal carbonyl stress induced by MG. First, we showed that polysulfides could protect differentiated (df)-SH-SY5Y cells from MG-induced cytotoxicity. When cells were pretreated with polysulfides, MG-induced cytotoxicity was attenuated with a rapid decrease in intracellular MG levels. Moreover, we found that polysulfides significantly suppressed the formation of MG-modified proteins in df-SH-SY5Y cells. Although polysulfide treatment increased endogenous GSH levels in the neuronal cells, its effects on MG-induced cytotoxicity were not affected by GSH concentration. Our results demonstrated that polysulfides had the direct potentials to protect neuronal cells against MG separate to the enzymatic detoxification system that required GSH. PMID:27163164

  18. The Interactions Between Aligned Poly(L-Lactic Acid) Nanofibers and SH-SY5Y Cells In Vitro.

    PubMed

    Yu, Yadong; Meng, Dianhuai; Man, Lili; Wang, Xin

    2016-06-01

    Aligned nanofibers have been regarded as promising nanomaterials in facilitating nerve regeneration. Investigating the interactions between aligned nanofibers and neuronal cells will be critically important for the design and application of aligned nanofibers in nerve tissue engineering. In this study, we explored the effects of electrospun Poly(L-Lactic Acid) (PLLA) aligned nanofibers on SH-SY5Y cells (a type of human neuroblastoma cell line) and specifically focused on the role of integrin in the PLLA aligned nanofiber-SH-SY5Y cell interaction. We found that PLLA aligned nanofibers could significantly guide the neurite outgrowth of SH-SY5Y cell, and promote the viability, proliferation, glucose and lactic acid metabolism of SH-SY5Y cell. This promotion effect could be alleviated when the functions of integrins on the SH-SY5Y cell membrane were hampered by pentapeptide GRGDS. Moreover, we found that PLLA aligned nanofibers could enhance the expression of phosphorylated-ERK1/2 (p-ERK1/2) in the SH-SY5Y cells and blocking the integrins would decrease p-ERK1/2 expression. These results suggested that PLLA aligned nanofibers might affect many cellular behaviors of SH-SY5Y cells via integrin mediated ERK pathway. Our findings provided more insights for understanding the interaction between aligned nanofibers and neuronal cells. PMID:27427727

  19. Changes in vitamin D supplement use and baseline plasma 25-hydroxyvitamin D concentration predict 5-y change in concentration in postmenopausal women.

    PubMed

    Kluczynski, Melissa A; Wactawski-Wende, Jean; Platek, Mary E; DeNysschen, Carol A; Hovey, Kathleen M; Millen, Amy E

    2012-09-01

    Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L). PMID:22833661

  20. Cyclic Deformation Response of β-Annealed Ti-5Al-5V-5Mo-3Cr Alloy Under Compressive Loading Conditions

    NASA Astrophysics Data System (ADS)

    Huang, Jun; Wang, Zhirui; Zhou, Jie

    2011-09-01

    This article reports the cyclic deformation behavior of the β-annealed metastable Ti-5Al-5V-5Mo-3Cr (Ti-5553) alloy under the condition of pure compressive fatigue stress. The following three aspects, namely, the mechanical response, the surface morphology evolution, and the dislocation structures, were systematically investigated. Under all testing conditions, the material demonstrated cyclic softening in the initial cycles followed by saturation. The progressive observation of surface morphology at fixed locations, but after different numbers of cycles, elucidated typical planar slip behavior and the early appearance of fatigue microcracks, which were found often to be induced by the highly localized planar slip bands. The transmission electron microscopy (TEM) study revealed dislocation annihilation upon cycling, i.e., the reduction of dislocation density as well as the simplification of dislocation configurations. In addition, detwinning and changed twin boundary structures upon cycling were also detected. Such activities, together with the intersection of coherent ω precipitates by moving dislocations, are considered to be responsible for the initial softening, whereas the dislocation dipole flip-flop mechanism is presumably responsible for the cyclic saturation behavior. An attempt was made to explain the strain-localized planar slip behavior by considering the stacking fault energy (SFE) as well as the free-electron-to-atom ( e/ a) ratio. The nanoscaled ω and α precipitation in the β matrix may also contribute to the planar slip behavior. The effect of the microstructure in the as-received material was also analyzed for the strain localization and planar-slip mode.

  1. Neuroprotective effects of tenuigenin in a SH-SY5Y cell model with 6-OHDA-induced injury.

    PubMed

    Liang, Zhigang; Shi, Fang; Wang, Yong; Lu, Li; Zhang, Zhanjun; Wang, Xuan; Wang, Xiaomin

    2011-06-22

    Tenuigenin, an active component of Polygala tenuifolia root extracts, has been shown to provide antioxidative and anti-aging effects in Alzheimer's disease, as well as to promote proliferation and differentiation of neural progenitor cells. However, the effects of tenuigenin on Parkinson's disease remain unclear. In the present study, SH-SY5Y cells were utilized to determine the effects of tenuigenin on 6-hydroxydopamine (6-OHDA)-induced injury. Results showed that 1.0 × 10⁻¹-10 μM tenuigenin significantly promoted cell viability and reduced cell death. In addition, tenuigenin protected mitochondrial membrane potential (MMP) against 6-OHDA damage and significantly increased glutathione and superoxide dismutase expression. At the mRNA level, tenuigenin resulted in down-regulation of caspase-3, but up-regulation of tyrosine hydroxylase expression in 6-OHDA damaged cells. These results suggested that tenuigenin provides neuroprotection to dopaminergic neurons from 6-OHDA-induced damage. The neuroprotective mechanisms might involve antioxidative effects, maintenance of mitochondrial function, and regulation of caspase-3 and tyrosine hydroxylase expression and activity. Tenuigenin could provide a novel antioxidative strategy for Parkinson's disease. PMID:21536104

  2. Cyclophilin B protects SH-SY5Y human neuroblastoma cells against MPP(+)-induced neurotoxicity via JNK pathway.

    PubMed

    Oh, Yoojung; Jeong, Kwon; Kim, Kiyoon; Lee, Young-Seok; Jeong, Suyun; Kim, Sung Soo; Yoon, Kyung-Sik; Ha, Joohun; Kang, Insug; Choe, Wonchae

    2016-09-23

    Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. PD involves a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyidine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) inhibit the complex I of the mitochondrial electron transport chain, and have been widely used to construct PD models. Cyclophilin B (CypB) is an endoplasmic reticulum protein that binds to cyclosporine A as a cyclophilin family member. CypB has peptidyl-prolyl cis-trans isomerase (PPIase) activity. We investigated the protective effects of overexpressed CypB on MPP+-induced neurocytotoxicity in SH-SY5Y human neuroblastoma cells. Overexpressed CypB decreased MPP(+)-induced oxidative stress through the modulation of antioxidant enzymes including manganese superoxide dismutase and catalase, and prevented neurocytotoxicity via mitogen-activated protein kinase, especially the c-Jun N-terminal kinase pathway. In addition, CypB inhibited the activation of MPP(+)-induced the pro-apoptotic molecules poly (ADP-ribose) polymerase, Bax, and Bcl-2, and attenuated MPP(+)-induced mitochondrial dysfunction. The data suggest that overexpressed CypB protects neuronal cells from MPP+-induced dopaminergic neuronal cell death. PMID:27569281

  3. Neuroprotective effects of orientin on hydrogen peroxide‑induced apoptosis in SH‑SY5Y cells.

    PubMed

    Law, Benjamin Ngee Tiing; Ling, Anna Pick Kiong; Koh, Rhun Yian; Chye, Soi Moi; Wong, Ying Pei

    2014-03-01

    Neurodegenerative diseases remain a global issue which affects the ageing population. Efforts towards determining their aetiologies to understand their pathogenic mechanisms are underway in order to identify a pathway through which therapeutic measures can be applied. One such pathogenic mechanism, oxidative stress (OS), is widely considered to be involved in neurodegenerative disease. Antioxidants, most notably flavonoids, have promising potential for therapeutic use as shown in in vitro and in vivo studies. In view of the importance of flavonoids for combating OS, this study investigated the neuroprotective effects of orientin, which has been reported to be capable of crossing the blood‑brain barrier. The maximum non‑toxic dose (MNTD) of orientin against SH‑SY5Y neuroblastoma cells was determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. The effects of the MNTD and the half MNTD (½MNTD) of orientin on cell cycle progression and intracellular reactive oxygen species (ROS) levels, as well as the activity of caspases 3/7, 8 and 9 after exposure to 150 µM of hydrogen peroxide (H2O2) were also determined using flow cytometry, a 2',7'‑dichlorodihydrofluorescein‑diacetate (DCFH‑DA) assay and caspase assay kits, respectively. The results revealed that orientin at ≤20 µM was not cytotoxic to SH‑SY5Y cells. After treatment with orientin at the MNTD, the percentage of apoptotic cells was significantly reduced compared with that in cells treated with 150 µM H2O2 alone. The results also showed that, although orientin at the MNTD and ½MNTD did not reduce intracellular ROS levels, it significantly inhibited the activity of caspases 3/7. Caspase 9 was significantly inactivated with orientin at the MNTD. Findings from this study suggest that the neuroprotection conferred by orientin was the result of the intracellular mediation of caspase activity. PMID:24366367

  4. Baicalin protects against thrombin induced cell injury in SH-SY5Y cells

    PubMed Central

    Ju, Xiao-Ning; Mu, Wei-Na; Liu, Yuan-Tao; Wang, Mei-Hong; Kong, Feng; Sun, Chao; Zhou, Qing-Bo

    2015-01-01

    Baicalin, an extract from the dried root of Scutellaria baicalensis Georgi, was shown to be neuroprotective. However, the precise mechanisms are incompletely known. In this study, we determined the effect of baicalin on thrombin induced cell injury in SH-SY5Y cells, and explored the possible mechanisms. SH-SY5Y cells was treated with thrombin alone or pre-treated with baicalin (5, 10, 20 μM) for 2 h followed by thrombin treatment. Cells without thrombin and baicalin treatment were used as controls. Cell viability was detected by MTT assay. Cell apoptosis was analyzed by flow cytometry. Real-time PCR was performed to determine the mRNA expression of protease-activated receptor-1 (PAR-1). Western blotting was conducted to determine the protein expression of PAR-1, Caspase-3 and NF-κB. Baicalin reduced cell death following thrombin treatment in a dose-dependent manner, with concomitant inhibition of NF-κB activation and suppression of PAR-1 expression. In addition, baicalin reduced Caspase-3 expression. The above findings indicated that baicalin prevents against cell injury after thrombin stimulation possibly through inhibition of PAR-1 expression and NF-κB activation. PMID:26823714

  5. Opioid agonists binding and responses in SH-SY5Y cells

    NASA Technical Reports Server (NTRS)

    Costa, E. M.; Hoffmann, B. B.; Loew, G. H.

    1992-01-01

    SH-SY5Y (human neuroblastoma) cultured cells, known to have mu-opioid receptors, have been used to assess and compare the ability of eight representative mu-selective compounds from diverse opioid families to recognize and activate these receptors. A wide range of receptor affinities spanning a factor of 10,000 was found between the highest affinity fentanyl analogs (Ki = 0.1nM) and the lowest affinity analog, meperidine (Ki = 1 microM). A similar range was found for inhibition of PGE1-stimulated cAMP accumulation with a rank order of activities that closely paralleled binding affinities. Maximum inhibition of cAMP accumulation by each compound was about 80%. Maximum stimulation of GTPase activity (approximately 50%) was also similar for all compounds except the lowest affinity meperidine. Both effects were naloxone reversible. These results provide further evidence that mu-receptors are coupled to inhibition of adenylate cyclase and that the SH-SY5Y cell line is a good system for assessment of mu-agonists functional responses.

  6. Gender Differences in Homicide of Neonates, Infants, and Children under 5 y in South Africa: Results from the Cross-Sectional 2009 National Child Homicide Study

    PubMed Central

    Abrahams, Naeemah; Mathews, Shanaaz; Martin, Lorna J.; Lombard, Carl; Nannan, Nadine; Jewkes, Rachel

    2016-01-01

    Background Homicide of children is a global problem. The under-5-y age group is the second largest homicide age group after 15–19 y olds, but has received little research attention. Understanding age and gender patterns is important for assisting with developing prevention interventions. Here we present an age and gender analysis of homicides among children under 5 y in South Africa from a national study that included a focus on neonaticide and infanticide. Methods and Findings A retrospective national cross-sectional study was conducted using a random sample of 38 medico-legal laboratories operating in 2009 to identify homicides of children under 5 y. Child data were abstracted from the mortuary files and autopsy reports, and both child and perpetrator data data were collected from police interviews. We erred towards applying a conservative definition of homicide and excluded sudden infant death syndrome cases. We estimated that 454 (95% CI 366, 541) children under the age of 5 y were killed in South Africa in 2009. More than half (53.2%; 95% CI 46.7%, 59.5%) were neonates (0–28 d), and 74.4% (95% CI 69.3%, 78.9%) were infants (under 1 y), giving a neonaticide rate of 19.6 per 100,000 live births and an infanticide rate of 28.4 per 100,000 live births. The majority of the neonates died in the early neonatal period (0–6 d), and abandonment accounted for 84.9% (95% CI 81.5%, 87.8%) of all the neonates killed. Distinct age and gender patterns were found, with significantly fewer boy children killed in rural settings compared to urban settings (odds ratio 0.6; 95% CI 0.4, 0.9; p = 0.015). Abuse-related killings and evidence of sexual assault were more common among older girls than in all other age and gender groups. Mothers were identified as the perpetrators in all of the neonaticides and were the most common perpetrators overall (71.0%; 95% CI 63.9%, 77.2%). Abandoned neonates were mainly term babies, with a mean gestational age of 38 wk. We did not have

  7. Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation.

    PubMed

    Dias, Irundika H K; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M; Polidori, Maria C; Lip, Gregory Y H; Griffiths, Helen R

    2014-10-01

    Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4μg oxLDL and 25µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. PMID:25048970

  8. Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation

    PubMed Central

    Dias, Irundika H.K.; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M.; Polidori, Maria C.; Lip, Gregory Y.H.; Griffiths, Helen R.

    2014-01-01

    Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4 μg oxLDL and 25 µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. PMID:25048970

  9. Differential effects of "Advanced glycation endproducts" and beta-amyloid peptide on glucose utilization and ATP levels in the neuronal cell line SH-SY5Y.

    PubMed

    Kuhla, B; Loske, C; Garcia De Arriba, S; Schinzel, R; Huber, J; Münch, G

    2004-03-01

    Beta-amyloid peptide (Abeta) and "Advanced glycation endproducts" (AGEs) are components of the senile plaques in Alzheimer's disease patients. It has been proposed that both AGEs and Abeta exert many of their effects, which include the upregulation of pro-inflammatory cytokines, through RAGE ("receptor for advanced glycation endproducts"). To investigate whether Abeta and AGEs cause similar or identical effects on cell survival and energy metabolism, we have compared the effects of a model-AGE and Abeta on cell viability, ATP level, glucose consumption and lactate production in the neuroblastoma cell line SH-SY5Y. The results show that AGEs and Abeta increase glucose consumption and decrease ATP levels in a dose dependent manner. Furthermore, both compounds decrease mitochondrial activity measured by the MTT assay. However, only AGEs decrease the number of cells and significantly increase lactate production. These data indicate that both AGEs and Abeta can cause differential disturbances in neuronal metabolism, which may contribute to the pathophysiological findings in Alzheimer's disease. However, their signalling pathways are apparently quite distinct, a fact which should stimulate a more detailed investigation in this field, e.g. for the purpose of a rational design of potential "neuroprotective" RAGE antagonists. PMID:14991463

  10. The Relationships Between Microstructure, Tensile Properties and Fatigue Life in Ti-5Al-5V-5Mo-3Cr-0.4Fe (Ti-5553)

    NASA Astrophysics Data System (ADS)

    Foltz, John W., IV

    beta-titanium alloys are being increasingly used in airframes as a way to decrease the weight of the aircraft. As a result of this movement, Ti-5Al-5V-5Mo-3Cr-0.4Fe (Timetal 555), a high-strength beta titanium alloy, is being used on the current generation of landing gear. This alloy features good combinations of strength, ductility, toughness and fatigue life in alpha+beta processed conditions, but little is known about beta-processed conditions. Recent work by the Center for the Accelerated Maturation of Materials (CAMM) research group at The Ohio State University has improved the tensile property knowledge base for beta-processed conditions in this alloy, and this thesis augments the aforementioned development with description of how microstructure affects fatigue life. In this work, beta-processed microstructures have been produced in a Gleeble(TM) thermomechanical simulator and subsequently characterized with a combination of electron and optical microscopy techniques. Four-point bending fatigue tests have been carried out on the material to characterize fatigue life. All the microstructural conditions have been fatigue tested with the maximum test stress equal to 90% of the measured yield strength. The subsequent results from tensile tests, fatigue tests, and microstructural quantification have been analyzed using Bayesian neural networks in an attempt to predict fatigue life using microstructural and tensile inputs. Good correlation has been developed between lifetime predictions and experimental results using microstructure and tensile inputs. Trained Bayesian neural networks have also been used in a predictive fashion to explore functional dependencies between these inputs and fatigue life. In this work, one section discusses the thermal treatments that led to the observed microstructures, and the possible sequence of precipitation that led to these microstructures. The thesis then describes the implications of microstructure on fatigue life and

  11. SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP(+) and rotenone.

    PubMed

    Knaryan, Varduhi H; Samantaray, Supriti; Park, Sookyoung; Azuma, Mitsuyoshi; Inoue, Jun; Banik, Naren L

    2014-07-01

    Complex pathophysiology of Parkinson's disease involves multiple CNS cell types. Degeneration in spinal cord neurons alongside brain has been shown to be involved in Parkinson's disease and evidenced in experimental parkinsonism. However, the mechanisms of these degenerative pathways are not well understood. To unravel these mechanisms SH-SY5Y neuroblastoma cells were differentiated into dopaminergic and cholinergic phenotypes, respectively, and used as cell culture model following exposure to two parkinsonian neurotoxicants MPP(+) and rotenone. SNJ-1945, a cell-permeable calpain inhibitor was tested for its neuroprotective efficacy. MPP(+) and rotenone dose-dependently elevated the levels of intracellular free Ca(2+) and induced a concomitant rise in the levels of active calpain. SNJ-1945 pre-treatment significantly protected cell viability and preserved cellular morphology following MPP(+) and rotenone exposure. The neurotoxicants elevated the levels of reactive oxygen species more profoundly in SH-SY5Y cells differentiated into dopaminergic phenotype, and this effect could be attenuated with SNJ-1945 pre-treatment. In contrast, significant levels of inflammatory mediators cyclooxygenase-2 (Cox-2 and cleaved p10 fragment of caspase-1) were up-regulated in the cholinergic phenotype, which could be dose-dependently attenuated by the calpain inhibitor. Overall, SNJ-1945 was efficacious against MPP(+) or rotenone-induced reactive oxygen species generation, inflammatory mediators, and proteolysis. A post-treatment regimen of SNJ-1945 was also examined in cells and partial protection was attained with calpain inhibitor administration 1-3 h after exposure to MPP(+) or rotenone. Taken together, these results indicate that calpain inhibition is a valid target for protection against parkinsonian neurotoxicants, and SNJ-1945 is an efficacious calpain inhibitor in this context. SH-SY5Y cells, differentiated as dopaminergic (TH positive) and cholinergic (ChAT positive), were

  12. Rosiglitazone protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity

    SciTech Connect

    Jung, Tae Woo; Lee, Ji Young; Shim, Wan Sub; Kang, Eun Seok; Kim, Soo Kyung; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo . E-mail: bscha@yumc.yonsei.ac.kr

    2006-02-03

    Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of the intracellular reactive oxygen species level and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor-{gamma} agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In this study, we investigated the protective effects of rosiglitazone on acetaldehyde-induced apoptosis in human neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde-induced apoptosis was moderately reversed by rosiglitazone treatment. Our results suggest that the protective effects of rosiglitazone on acetaldehyde-induced apoptosis may be ascribed to ability to induce the expression of anti-oxidant enzymes and to regulate Bcl-2 and Bax expression. These data indicate that rosiglitazone may provide a useful therapeutic strategy for the prevention of progressive neurodegenerative disease such as Parkinson's disease.

  13. Sodium orthovanadate induces the apoptosis of SH-SY5Y cells by inhibiting PIWIL2.

    PubMed

    Tian, Xiaohong; Fan, Jun; Hou, Weijian; Bai, Shuling; Ao, Qiang; Tong, Hao

    2016-01-01

    PIWIs have been shown to be abnormally expressed in a variety of cancers and may be important in the maintenance and invasion of cancer cells. The high expression of PIWIL2 contributed to the resistance effect of cisplatin in colon cancer cells, and the knockout of the PIWIL2 gene reduced the aggressive nature and malignant degree of colon cancer cells. Sodium orthovanadate (SOV) is a vanadium compound, and exhibited antineoplastic activity in certain types of human cancer cells, including lung, kidney and prostate cancer cells. However, its effects in human neuroblastoma (NB) cells have not yet been reported. The objective of this study was to investigate the effect of SOV on the apoptosis of NB cells and to explore how PIWIL2 is involved in the mechanism underlying this effect. In the present study, SH‑SY5Y cells were treated with SOV and the optimal concentration was determined for further assays. Cell apoptosis, cell count, viability, the cell cycle, and the expression of PIWIL2 mRNA and protein were then determined. The results showed that SOV could induce cell apoptosis, reduce the percentage of viable cells, induce accumulation of SH‑SY5Y cells at the G2/M and S phase of the cell cycle, and inhibit the expression of PIWIL2 and Bcl‑2 mRNA and protein. The results suggested that the underlying mechanisms may be, at least in part, due to SOV inhibiting the expression of PIWIL2. These findings demonstrated the effect of SOV and supported its further evaluation as a treatment for human NB. PMID:26647781

  14. Neuroprotective effect of Amaranthus lividus and Amaranthus tricolor and their effects on gene expression of RAGE during oxidative stress in SH-SY5Y cells.

    PubMed

    Amornrit, W; Santiyanont, R

    2016-01-01

    Amaranthus plants, or spinach, are used as food sources worldwide. Amaranthus leaves are rich in antioxidant compounds, which act as free radical scavengers. Oxidative stress caused by the aberrant production of reactive oxygen species (ROS) represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective effects of antioxidant-containing plants have been extensively demonstrated in different models of neurotoxicity. However, few studies have investigated the antioxidant properties of Amaranthus extracts and their effect on the nervous system. In the present study, the leaves of Amaranthus lividus and Amaranthus tricolor were extracted using petroleum ether, dichloromethane, and methanol. Results indicated that antioxidant activities were the highest in methanol extracts from both kinds of Amaranthus leaves. In addition, oxidative stress was induced in human neuroblastoma cell lines (SH-SY5Y) by using H2O2. Intracellular oxidative stress, cytotoxicity, and gene expression of RAGE were then determined. In vitro results demonstrated that pretreatment with A. lividus and A. tricolor extracts can significantly decrease cell toxicity and intracellular ROS production in SH-SY5Y cells. Interestingly, the extracts also significantly downregulated the expression of oxidative stress genes such as HMOX-1, RAGE, and RelA/ NF-κB. Our results suggested that Amaranthus leaves may be useful for reducing oxidative stress and may be beneficial for age-related diseases and neurodegenerative disorders. PMID:27173239

  15. Synthesis, crystal structure and properties of alluaudite-like triple molybdate Na{sub 25}Cs{sub 8}Fe{sub 5}(MoO{sub 4}){sub 24}

    SciTech Connect

    Savina, Aleksandra A.; Solodovnikov, Sergey F.; Belov, Dmitry A.; Basovich, Olga M.; Solodovnikova, Zoya A.; Pokholok, Konstantin V.; Stefanovich, Sergey Yu.; Lazoryak, Bogdan I.; Khaikina, Elena G.

    2014-12-15

    A new triple molybdate Na{sub 25}Cs{sub 8}Fe{sub 5}(MoO{sub 4}){sub 24} was synthesized using solid state reactions and studied with X-ray powder diffraction, second harmonic generation (SHG) technique, differential scanning calorimetry, Mössbauer and dielectric impedance spectroscopy. Single crystals of Na{sub 25}Cs{sub 8}Fe{sub 5}(MoO{sub 4}){sub 24} were obtained and its structure was solved (the space group P1{sup ¯}, a=12.5814(5), b=13.8989(5), c=28.4386(9) Å, α=90.108(2), β=90.064(2), γ=90.020(2)°, V=4973.0(3) Å{sup 3}, Z=2, R=0.0440). Characteristic features of the structure are polyhedral layers composed of pairs of edge-shared FeO{sub 6} and (Fe, Na)O{sub 6} octahedra, which are connected by bridging MoO{sub 4} tetrahedra. The layers share common vertices with bridging MoO{sub 4} tetrahedra to form an open 3D framework with the cavities occupied by the Cs{sup +} and Na{sup +} cations. The compound undergoes first-order phase transformation at 642 K and above this phase transition, electrical conductivity reaches 10{sup −3}–10{sup −2} S cm{sup −1}. Thus, Na{sub 25}Cs{sub 8}Fe{sub 5}(MoO{sub 4}){sub 24} may be considered as a promising compound for developing new materials with high ionic conductivity. - Graphical abstract: A new triple molybdate Na{sub 25}Cs{sub 8}Fe{sub 5}(MoO{sub 4}){sub 24} was synthesized and structurally characterized, its physicochemical properties were studied. - Highlights: • New compound Na{sub 25}Cs{sub 8}Fe{sub 5}(MoO{sub 4}){sub 24} was synthesized. • Physicochemical properties of the compound were studied. • The first-order phase transformation is observed. • Electrical conductivity above 642 K is (10{sup −2}–10{sup −3}) S cm{sup −1}. • New compound may be considered as promising object with high ionic conductivity.

  16. Analysis of subcellular [57Co] cobalamin distribution in SH-SY5Y neurons and brain tissue.

    PubMed

    Zhao, Hua; Ruberu, Kalani; Li, Hongyun; Garner, Brett

    2013-07-15

    Cobalamin (Cbl) utilization as a cofactor for methionine synthase and methylmalonyl-CoA mutase is dependent on the transport of Cbl through lysosomes and its subsequent delivery to the cytosol and mitochondria. We speculated that neuropathological conditions that impair lysosomal function (e.g., age-related lipofuscinosis and specific neurodegenerative diseases) might impair lysosomal Cbl transport. To address this question, an appropriate method to quantify intracellular Cbl transport in neuronal cell types and brain tissue is required. Thus, we developed methods to measure [57Co] Cbl levels in lysosomes, mitochondria and cytosol obtained from in vitro and in vivo sources. Human SH-SY5Y neurons or HT1080 fibroblasts were labeled with [57Co] Cbl and homogenized using a ball-bearing homogenizer, and the lysates were separated into 10 fractions using ultracentrifugation in an OptiPrep density gradient. Lysosomes were recovered from the top of the gradient (fractions 1-5), which were clearly separated from mitochondria (fractions 7-9) on the basis of the expression of the marker proteins, LAMP2 and VDAC1. The isolated lysosomes were intact based on their colocalization with acid phosphatase activity. The lysosomal and mitochondrial fractions were free of the cytosolic markers beta-actin and methionine synthase. The relative distribution of [57Co] Cbl in both neurons and fibroblasts was as follows: 6% in the lysosomes, 14% in the mitochondria and 80% in the cytosol. This technique was also used to fractionate organelles from mouse brain, where marker proteins were detected in the gradient at positions similar to those observed for the cell lines, and the relative distribution of [57Co] Cbl was as follows: 12% in the lysosomes, 15% in the mitochondria and 73% in the cytosol. These methods provide a useful tool for the investigation of intracellular Cbl trafficking in a neurobiological setting. PMID:23608310

  17. Zinc oxide nanoparticles and SH-SY5Y cell line

    NASA Astrophysics Data System (ADS)

    Zheng, Jinghui

    The Arctic and sub-arctic regions are impacted by the growth of the global nanotechnology industry. Nanomaterials have unique chemical and physical properties that may lead to toxicological effects that interfere with normal cellular metabolism. Zinc oxide nanoparticles (ZnO NPs) are now very common and widely used in daily life. In industry, ZnO NPs are used to protect different materials from damage caused by UV exposure. The scientific literature suggests that ZnO NPs can have negative impacts on both living organisms and plants. However, there is a paucity of research on the mechanisms by which ZnO NPs may affect the neuronal cells. This study investigates how ZnO NPs interact with the neuroblastoma cell line SH-SY5Y. Using transmission electron microscopy, we observed that the ZnO NPs form 36 nm particles on average, and increase the level of vascular endothelial growth factor (VEGF) in extracellular fluid, as measured by an enzyme-linked immunosorbent assay (ELISA). Moreover, ZnO NPs, in presence of tumor necrosis factor-alpha (TNF-alpha), can also decrease the level of extracellular VEGF compared with TNF-alpha treatment alone. These findings suggest the basis for more studies on understanding the mechanism by which ZnO NPs impact cytokine signaling. Another direction is using ELISA technology to observe the interactions of NPs with different cell types such as neuronal stem cells.

  18. N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line.

    PubMed

    Maddirala, Yasaswi; Tobwala, Shakila; Ercal, Nuran

    2015-05-22

    Manganese (Mn) is an essential trace element required for normal cellular functioning. However, overexposure of Mn can be neurotoxic resulting in the development of manganism, a syndrome that resembles Parkinson׳s disease. Although the pathogenetic basis of this disorder is unclear, several studies indicate that it is mainly associated with oxidative stress and mitochondrial energy failure. Therefore, this study is focused on (1) investigating the oxidative effects of Mn on neuroblastoma cells (SHSY5Y) and (2) elucidating whether a novel thiol antioxidant, N-acetylcysteineamide (NACA), provides any protection against Mn-induced neurotoxicity. Reactive oxygen species (ROS) were highly elevated after the exposure, indicating that mechanisms that induce oxidative stress were involved. Measures of oxidative stress parameters, such as glutathione (GSH), malondialdehyde (MDA), and activities of glutathione reductase (GR) and glutathione peroxidase (GPx) were altered in the Mn-treated groups. Loss of mitochondrial membrane potential, as assessed by flow cytometry and decreased levels of ATP, indicated that cytotoxicity was mediated through mitochondrial dysfunction. However, pretreatment with NACA protected against Mn-induced toxicity by inhibiting lipid peroxidation, scavenging ROS, and preserving intracellular GSH and mitochondrial membrane potential. NACA can potentially be developed into a promising therapeutic option for Mn-induced neurotoxicity. This article is part of a Special Issue entitled SI: Metals in neurodegeneration. PMID:25681547

  19. Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells.

    PubMed

    Song, Mee; Song, Mi-Kyung; Choi, Han-Seam; Ryu, Jae-Chun

    2013-06-01

    Iodothyronine deiodinase types I, II, and III (D1, D2, and D3, respectively), which constitute a family of selenoenzymes, activate and inactivate thyroid hormones through the removal of specific iodine moieties from thyroxine and its derivatives. These enzymes are important in the biological effects mediated by thyroid hormones. The expression of activating and inactivating deiodinases plays a critical role in a number of cell systems, including the neuronal system, during development as well as in adult vertebrates. To investigate deiodinase-disrupting chemicals based on transcriptomic responses, we examined differences in gene expression profiles between T3-treated and deiodinase-knockdown SH-SY5Y cells using microarray analysis and quantitative real-time RT-PCR. A total of 1,558 genes, consisting of 755 upregulated and 803 downregulated genes, were differentially expressed between the T3-treated and deiodinase-knockdown cells. The expression levels of 10 of these genes (ID2, ID3, CCL2, TBX3, TGOLN2, C1orf71, ZNF676, GULP1, KLF9, and ITGB5) were altered by deiodinase-disrupting chemicals (2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyls, propylthiouracil, iodoacetic acid, methylmercury, β-estradiol, methimazole, 3-methylcholanthrene, aminotriazole, amiodarone, cadmium chloride, dimethoate, fenvalerate, octylmethoxycinnamate, iopanoic acid, methoxychlor, and 4-methylbenzylidene-camphor). These genes are potential biomarkers for detecting deiodinase deficiency and predicting their effects on thyroid hormone production. PMID:23397585

  20. Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury

    PubMed Central

    Liu, Yang; Zhang, Ren-Yu; Zhao, Jun; Dong, Zheng; Feng, Dong-Yun; Wu, Rui; Shi, Ming; Zhao, Gang

    2015-01-01

    Ginsenoside Rd (GSRd), one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD) model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+), an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results, from the addition of different concentrations of GSRd (1, 10 and 50 μM), showed that GSRd at 1 and 10 μM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation. PMID:26114390

  1. Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells.

    PubMed

    Takahashi, Muneaki; Chin, Yo; Nonaka, Takashi; Hasegawa, Masato; Watanabe, Nobuo; Arai, Takao

    2012-02-21

    Presence of cytoplasmic tau aggregates is a hallmark of brains in patients with tauopathies such as Alzheimer's disease. However, the mechanism underlying formation of these insoluble tau aggregates remains elusive. In this study, we investigated the impact of prolonged nitric oxide (NO) exposure on neuronal SH-SY5Y cells overexpressing human tau. Treatment with the NO donor DETA NONOate for up to 48h resulted in an increase in S-nitrosation of cellular proteins, inactivation of proteasome, and impairment of respiration. Western blot analysis of Triton X-soluble fractions of NO-treated cells revealed that persistent NO treatment increased heterogeneity in tau molecule size, as a result of dephosphorylation, and induced the formation of sodium dodecyl sulfate (SDS)-stable oligomeric tau aggregates, stabilized by disulfide bonds. Moreover, further NO treatment induced the formation of SDS-stable insoluble tau mega-aggregates that were composed of dephosphorylated full-length tau molecules and other proteins, and were stabilized through disulfide bonds. Evaluation of the role of these tau aggregates as potential seeds for tau fibrillization and elucidation of their formation mechanism in our model, could lead to better understanding of the pathogenesis of tauopathies. PMID:22249117

  2. Characterization of catechol-thioether-induced apoptosis in human SH-SY5Y neuroblastoma cells.

    PubMed

    Mosca, Luciana; Tempera, Italo; Lendaro, Eugenio; Di Francesco, Laura; d'Erme, Maria

    2008-03-01

    Recent work has highlighted the involvement of a dopamine derivative, 5-S-cysteinyl-dopamine (CysDA), in neurodegeneration and apoptotic cell death. In this paper we study in further detail the apoptotic process activated by this catechol-thioether derivative of dopamine in SH-SY5Y neuroblastoma cells. CysDA activates a cascade of events by an initial perturbation of Calcium homeostasis in the cell. Cell treatment with the catechol-thioether induces an immediate rise in intracellular Ca(2+) concentration, as demonstrated by a shift in the indo-1 dye emission spectrum, and a sustained high calcium concentration at long times of incubation. Fluorescence microscopy data show that the treatment of cells induces mitochondrial transmembrane potential depolarization, a clear evidence of the onset of apoptotic process. Programmed cell death activation is also demonstrated by cytochrome c release from the mitochondria, by an increased activity of both caspase-8 and -9 and by the poly(ADP-ribose)polymerase (PARP-1) cleavage, yielding the typical 86 kDa fragment due to caspase-3 activity. Overall, our data support the hypothesis that CysDA may induce apoptotic death in neuronal cells, via an initial perturbation of calcium homeostasis in the cytosol. PMID:17929313

  3. Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury.

    PubMed

    Liu, Yang; Zhang, Ren-Yu; Zhao, Jun; Dong, Zheng; Feng, Dong-Yun; Wu, Rui; Shi, Ming; Zhao, Gang

    2015-01-01

    Ginsenoside Rd (GSRd), one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD) model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+), an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results, from the addition of different concentrations of GSRd (1, 10 and 50 μM), showed that GSRd at 1 and 10 μM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation. PMID:26114390

  4. Adult but Not Aged C57BL/6 Male Mice Are Capable of Using Geometry for Orientation

    ERIC Educational Resources Information Center

    Schachner, Melitta; Morellini, Fabio; Fellini, Laetitia

    2006-01-01

    Geometry, e.g., the shape of the environment, can be used by numerous animal species to orientate, but data concerning the mouse are lacking. We addressed the question of whether mice are capable of using geometry for navigating. To test whether aging could affect searching strategies, we compared adult (3- to 5-mo old) and aged (20- to 21-mo old)…

  5. Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Aβ1–42 expression

    PubMed Central

    WANG, YUN; LIU, TE; PAN, WEIDONG; CHI, HUIYING; CHEN, JIULIN; YU, ZHIHUA; CHEN, CHUAN

    2016-01-01

    Oxidative stress and ageing are important factors contributing to the pathogenesis of Alzheimer's disease (AD), which is associated with neuronal damage and β-amyloid (Aβ) deposition. The p66shc adaptor protein is important for the regulation of oxidative stress and ageing. In the present study, SH-SY5Y human neuroblastoma cells were treated with anisomycin in order to establish a cell model of oxidative stress-induced neuronal damage. The results from quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting demonstrated that anisomycin was able to stimulate the secretion of Aβ1–42 from SH-SY5Y cells and upregulate the expression levels of p66shc, which was associated with concomitant damage to SH-SY5Y cells. In addition, the protective effects of various small molecule compounds with antioxidant properties against neuronal damage were evaluated. Notably, treatment of SH-SY5Y cells with gallic acid was associated with significant downregulation of p66shc protein expression levels, reduced anisomycin-induced secretion of Aβ1–42, and increased superoxide dismutase activity and acetylcholine secretion levels. The results of the present study suggested that anisomycin is able to promote oxidative neuronal damage by inducing the secretion of Aβ1–42 from neurons and increasing the neuronal expression of p66shc, and this damage may be attenuated by treatment with gallic acid. Therefore, gallic acid and similar small molecule compounds may be considered for the alleviation of neuronal oxidative stress injury in patients with AD. PMID:26893652

  6. Investigation into the effect of molybdenum-site substitution on the performance of Sr2Fe1.5Mo0.5O6-δ for intermediate temperature solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Hou, Mingyue; Sun, Wang; Li, Pengfa; Feng, Jie; Yang, Guoquan; Qiao, Jinshuo; Wang, Zhenhua; Rooney, David; Feng, Jinsheng; Sun, Kening

    2014-12-01

    In this paper, niobium doping is evaluated as a means of enhancing the electrochemical performance of a Sr2Fe1.5Mo0.5O6-δ (SFM) perovskite structure cathode material for intermediate temperature solid oxide fuel cells (IT-SOFCs) applications. As the radius of Nb approximates that of Mo and exhibits +4/+5 mixed valences, its substitution is expected to improve material performance. A series of Sr2Fe1.5Mo0.5-xNbxO6-δ (x = 0.05, 0.10, 0.15, 0.20) cathode materials are prepared and the phase structure, chemical compatibility, microstructure, electrical conductivity, polarization resistance and power generation are systematically characterized. Among the series of samples, Sr2Fe1.5Mo0.4Nb0.10O6-δ (SFMNb0.10) exhibits the highest conductivity value of 30 S cm-1 at 550 °C, and the lowest area specific resistance of 0.068 Ω cm2 at 800 °C. Furthermore, an anode-supported single cell incorporating a SFMNb0.10 cathode presents a maximum power density of 1102 mW cm-2 at 800 °C. Furthermore no obvious performance degradation is observed over 15 h at 750 °C with wet H2 (3% H2O) as fuel and ambient air as the oxidant. These results demonstrate that SFMNb shows great promise as a novel cathode material for IT-SOFCs.

  7. Identification of alpha 2-adrenergic receptor sites in human retinoblastoma (Y-79) and neuroblastoma (SH-SY5Y) cells

    SciTech Connect

    Kazmi, S.M.; Mishra, R.K.

    1989-02-15

    The existence of specific alpha 2-adrenergic receptor sites has been shown in human retinoblastoma (Y-79) and neuroblastoma (SH-SH5Y) cells using direct radioligand binding. (/sup 3/H)Rauwolscine, a selective alpha 2-adrenergic receptor antagonist, exhibited high affinity, saturable binding to both Y-79 and SH-SY5Y cell membranes. The binding of alpha 1 specific antagonist, (/sup 3/H)Prazocine, was not detectable in either cell type. Competition studies with antagonists yielded pharmacological characteristics typical of alpha 2-adrenergic receptors: rauwolscine greater than yohimbine greater than phentolamine greater than prazocine. Based on the affinity constants of prazocine and oxymetazoline, it appears that Y-79 cells contain alpha 2A receptor, whereas SH-SY5Y cells probably represent a mixture of alpha 2A and alpha 2B receptors. alpha 2-agonists clonidine and (-)epinephrine inhibition curves yielded high and low affinity states of the receptor in SH-SY5Y cells. Gpp(NH)p and sodium ions reduced the proportion of high affinity sites of alpha 2 receptors. These two neuronal cell lines of human origin would prove useful in elucidating the action and regulation of human alpha 2-adrenergic receptors and their interaction with other receptor systems.

  8. Acetaldehyde Induces Cytotoxicity of SH-SY5Y Cells via Inhibition of Akt Activation and Induction of Oxidative Stress

    PubMed Central

    Yan, Tingting; Zhao, Yan; Zhang, Xia

    2016-01-01

    Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease. Acetaldehyde, the most toxic metabolite of ethanol, is speculated to mediate the brain tissue damage and cognitive dysfunction induced by the chronic excessive consumption of alcohol. However, the exact mechanisms by which acetaldehyde induces neurotoxicity are not totally understood. In this study, we investigated the cytotoxic effects of acetaldehyde in SH-SY5Y cells and found that acetaldehyde induced apoptosis of SH-SY5Y cells by downregulating the expression of antiapoptotic Bcl-2 and Bcl-xL and upregulating the expression of proapoptotic Bax. Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). In addition, acetaldehyde induced the activation of p38 mitogen-activated protein kinase (MAPK) while inhibiting the activation of extracellular signal-regulated kinases (ERKs, p44/p42MAPK). Meanwhile, acetaldehyde treatment caused an increase in the production of reactive oxygen species and elevated the oxidative stress in SH-SY5Y cells. Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress. PMID:26649137

  9. Analysis of Microstructural Evolution and Fracture Mechanisms in Ti-5Al-5V-5Mo-3Cr-0.4Fe in Response to Electron Beam Welding and Post Weld Heat Treatments

    NASA Astrophysics Data System (ADS)

    Sabol, Joseph C.

    Within the last half-century, advances in Ti and Ti alloys have increased their popularity in the aerospace industry as well as in commercial products. Some Ti alloys have even replaced steels and Ni-base alloys due to their high strength and superior corrosion resistance. Of the various Ti alloys, near-beta and metastable beta alloys have become more common since their first large-scale use in the SR-71 Blackbird. In particular, TIMET's Ti-5Al-5V-5Mo-3Cr (Timetal Ti555, Ti-5553) gained high attainable strengths, excellent forging characteristics, and increased sensitivity to heat treatments compared to other beta-Ti alloys. Ti-5553 has become widely known for its desirable attributes and has since become the baseline for the next generation of metastable beta and near-beta Ti alloys. However, as well known as Ti-5553 is in the aerospace and Ti industry, its responses to welding have, for the most part, gone uncharacterized. The work presented in this dissertation investigates the influence of electron beam welding and post weld heat treatments on the microstructural, mechanical, and fracture responses of Ti-5553. In this study, Ti-5553 was electron beam welded and heat-treated in accordance to three predetermined heat treatments: 700°C for 4 hours followed by air cooling to room temperature, 804°C for 1 hour followed by air cooling to room temperature, and 804°C for 1 hour followed by air cooling to room temperature then aging at 600°C for 4 hours followed by air cooling to room temperature. Subsequently, the mechanical properties, microstructure, solute partitioning, precipitate identities, and fracture characteristics were evaluated. With the use of traditional techniques and new technology it was shown that electron beam welded Ti-5553 in the as-welded condition and three post weld heat treatment conditions exhibited varying properties, distinctive to each of the corresponding microstructures. It was also found that the o-phase played a large role in the

  10. SPHK1/sphingosine kinase 1-mediated autophagy differs between neurons and SH-SY5Y neuroblastoma cells.

    PubMed

    Moruno Manchon, Jose Felix; Uzor, Ndidi-Ese; Finkbeiner, Steven; Tsvetkov, Andrey S

    2016-08-01

    Although implicated in neurodegeneration, autophagy has been characterized mostly in yeast and mammalian non-neuronal cells. In a recent study, we sought to determine if SPHK1 (sphingosine kinase 1), implicated previously in macroautophagy/autophagy in cancer cells, regulates autophagy in neurons. SPHK1 synthesizes sphingosine-1-phosphate (S1P), a bioactive lipid involved in cell survival. In our study, we discovered that, when neuronal autophagy is pharmacologically stimulated, SPHK1 relocalizes to the endocytic and autophagic organelles. Interestingly, in non-neuronal cells stimulated with growth factors, SPHK1 translocates to the plasma membrane, where it phosphorylates sphingosine to produce S1P. Whether SPHK1 also binds to the endocytic and autophagic organelles in non-neuronal cells upon induction of autophagy has not been demonstrated. Here, we determined if the effect in neurons is operant in the SH-SY5Y neuroblastoma cell line. In both non-differentiated and differentiated SH-SY5Y cells, a short incubation of cells in amino acid-free medium stimulated the formation of SPHK1-positive puncta, as in neurons. We also found that, unlike neurons in which these puncta represent endosomes, autophagosomes, and amphisomes, in SH-SY5Y cells SPHK1 is bound only to the endosomes. In addition, a dominant negative form of SPHK1 was very toxic to SH-SY5Y cells, but cultured primary cortical neurons tolerated it significantly better. These results suggest that autophagy in neurons is regulated by mechanisms that differ, at least in part, from those in SH-SY5Y cells. PMID:27467777

  11. Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol.

    PubMed

    Teppola, Heidi; Sarkanen, Jertta-Riina; Jalonen, Tuula O; Linne, Marja-Leena

    2016-04-01

    Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was to examine in the RA and CHOL treated SH-SY5Y cells the additive impacts of estradiol (E2) and brain-derived neurotrophic factor (BDNF) on cell morphology, cell population growth, synaptic vesicle recycling and presence of neurofilaments. The above features indicate a higher level of neuronal differentiation. Our data show that treatment for 10 days in vitro (DIV) with RA alone or when combined with E2 (RE) or CHOL (RC), but not when combined with BDNF (RB), significantly (p < 0.01) inhibited the cell population growth. Synaptic vesicle recycling, induced by high-K(+) depolarization, was significantly increased in all treatments where RA was included (RE, RC, RB, RCB), and when all agents were added together (RCBE). Specifically, our results show for the first time that E2 treatment can alone increase synaptic vesicle recycling in SH-SY5Y cells. This work contributes to the understanding of the ways to improve suppression of neuroblastoma cells' population growth by inducing maturation and differentiation. PMID:26518675

  12. Epigenetic Regulation of Cytosolic Phospholipase A2 in SH-SY5Y Human Neuroblastoma Cells.

    PubMed

    Tan, Charlene Siew-Hon; Ng, Yee-Kong; Ong, Wei-Yi

    2016-08-01

    Group IVA cytosolic phospholipase A2 (cPLA2 or PLA2G4A) is a key enzyme that contributes to inflammation via the generation of arachidonic acid and eicosanoids. While much is known about regulation of cPLA2 by posttranslational modification such as phosphorylation, little is known about its epigenetic regulation. In this study, treatment with histone deacetylase (HDAC) inhibitors, trichostatin A (TSA), valproic acid, tubacin and the class I HDAC inhibitor, MS-275, were found to increase cPLA2α messenger RNA (mRNA) expression in SH-SY5Y human neuroblastoma cells. Co-treatment of the histone acetyltransferase (HAT) inhibitor, anacardic acid, modulated upregulation of cPLA2α induced by TSA. Specific involvement of class I HDACs and HAT in cPLA2α regulation was further shown, and a Tip60-specific HAT inhibitor, NU9056, modulated the upregulation of cPLA2α induced by MS-275. In addition, co-treatment of with histone methyltransferase (HMT) inhibitor, 5'-deoxy-5'-methylthioadenosine (MTA) suppressed TSA-induced cPLA2α upregulation. The above changes in cPLA2 mRNA expression were reflected at the protein level by Western blots and immunocytochemistry. Chromatin immunoprecipitation (ChIP) showed TSA increased binding of trimethylated H3K4 to the proximal promoter region of the cPLA2α gene. Cell injury after TSA treatment as indicated by lactate dehydrogenase (LDH) release was modulated by anacardic acid, and a role of cPLA2 in mediating TSA-induced injury shown, after co-incubation with the cPLA2 selective inhibitor, arachidonoyl trifluoromethyl ketone (AACOCF3). Together, results indicate epigenetic regulation of cPLA2 and the potential of such regulation for treatment of chronic inflammation. PMID:26162318

  13. Structure, phase evolution, and microwave dielectric properties of (Ag0.5Bi0.5)(Mo0.5W0.5)O4 ceramic with ultralow sintering temperature.

    PubMed

    Zhou, Di; Li, Wen-Bo; Guo, Jing; Pang, Li-Xia; Qi, Ze-Ming; Shao, Tao; Xie, Hui-Dong; Yue, Zhen-Xing; Yao, Xi

    2014-06-01

    In the present work, the microwave dielectric ceramic (Ag0.5Bi0.5)(Mo0.5W0.5)O4 was prepared by using the solid-state reaction method. (Ag0.5Bi0.5)(Mo0.5W0.5)O4 was found to crystallize in the scheelite structure, in which Ag(+) and Bi(3+) occupy the A site randomly with 8-coordination while Mo(6+) and W(6+) occupy the B site with 4-coordination, at a sintering temperature above 500 °C, with lattice parameters a = b = 5.29469(2) Å and c = 11.62114(0) Å, space group I4(1)/a (No. 88), and acceptable Rp = 9.38, Rwp = 11.2, and Rexp = 5.86. High-performance microwave dielectric properties, with permittivity ∼26.3, Qf value ∼10,000 GHz, and temperature coefficient ∼+20 ppm/°C, were obtained in the sample sintered at 580 °C. Its chemical compatibility with aluminum at its sintering temperature was revealed and confirmed by both X-ray and energy dispersive spectrometer analysis. This ceramic could be a good candidate for ultralow-temperature cofired ceramics. PMID:24848200

  14. Na[subscript 1.5]Ag[subscript 1.5]MO[subscript 3]F[subscript 3] (M = Mo, W): An Ordered Oxyfluoride Derivative of the LiNbO[subscript 3] Structure

    SciTech Connect

    Fry, Allyson M.; Seibel, II, Harry A.; Lokuhewa, Indunil N.; Woodward, Patrick M.

    2012-04-02

    Na{sub 1.5}Ag{sub 1.5}MoO{sub 3}F{sub 3} and Na{sub 1.5}Ag{sub 1.5}WO{sub 3}F{sub 3} have been synthesized by solid state reactions and structurally characterized using synchrotron X-ray and neutron powder diffraction. Unlike the vast majority of salts containing [MO{sub 3}F{sub 3}]{sup 3-} anions (M = Mo, W) the oxyfluoride groups in Na{sub 1.5}Ag{sub 1.5}MoO{sub 3}F{sub 3} and Na{sub 1.5}Ag{sub 1.5}WO{sub 3}F{sub 3} are orientationally ordered, so that the Na{sup +} ions are coordinated by fluorine and the Ag{sup +} ions by oxygen. The resulting structure type, which has not previously been reported, is related to the LiNbO{sub 3} structure, but the combination of Na/Ag ordering and orientational ordering of the [MO{sub 3}F{sub 3}]{sup 3-} anions produces a supercell that doubles the c-axis and changes the space group symmetry from R3 to R{bar 3}. The use of hard (Na{sup +}) and soft (Ag{sup +}) cations to direct the orientational ordering of polar oxyfluoride building units provides a new approach to the design of polar materials.

  15. The Development of Multi-axial Creep Damage Constitutive Equations for 0.5Cr0.5Mo0.25V Ferritic Steel at 590°C

    NASA Astrophysics Data System (ADS)

    Xu, Qiang; Barrans, Simon

    Within the framework of a phenomenological approach a set of multi-axial creep damage constitutive equations for 0.5Cr0.5Mo0.25V ferritic steel at 590°C is developed in which a new formulation is employed. The deficiency of the previous formulation and the need for improvement became apparent after a critical review of the development of creep damage constitutive equations for 316 stainless steel(1). The need for improvement was further underpinned by a call for modification of the constitutive equations(36). Recently, a specific formulation was proposed and validated(2)-(4). This paper reports the latest developments of the multi-axial creep constitutive equations for 0.5Cr0.5Mo0.25V ferritic steel at 590°C including: 1) the fundamental requirement; 2) formulation; 3) validation; and 4) conclusion. It systematically shows the suitability of this new set of constitutive equations and the incapability of the previous ones. Furthermore, it contributes knowledge to the methodology.

  16. Effect of 8-hydroxyquinoline and derivatives on human neuroblastoma SH-SY5Y cells under high glucose

    PubMed Central

    Suwanjang, Wilasinee; Prachayasittikul, Supaluk

    2016-01-01

    8-Hydroxyquinoline and derivatives exhibit multifunctional properties, including antioxidant, antineurodegenerative, anticancer, anti-inflammatory and antidiabetic activities. In biological systems, elevation of intracellular calcium can cause calpain activation, leading to cell death. Here, the effect of 8-hydroxyquinoline and derivatives (5-chloro-7-iodo-8-hydroxyquinoline or clioquinol and 8-hydroxy-5-nitroquinoline or nitroxoline) on calpain-dependent (calpain-calpastatin) pathways in human neuroblastoma (SH-SY5Y) cells was investigated. 8-Hydroxyquinoline and derivatives ameliorated high glucose toxicity in SH-SY5Y cells. The investigated compounds, particularly clioquinol, attenuated the increased expression of calpain, even under high-glucose conditions. 8-Hydroxyquinoline and derivatives thus adversely affected the promotion of neuronal cell death by high glucose via the calpain-calpastatin signaling pathways. These findings support the beneficial effects of 8-hydroxyquinolines for further therapeutic development.

  17. Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating GRP78 in SH-SY5Y cells.

    PubMed

    Huang, Jingwei; Chen, Changyan; Gu, Hua; Li, Chen; Fu, Xing; Jiang, Ming; Sun, Hui; Xu, Jun; Fang, Jianmin; Jin, Lingjing

    2016-07-01

    Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects dopaminergic neurons from damage. In this study, we used MTT, immunohistochemistry, and TUNEL staining to investigate the protective effect of MANF in SH-SY5Y cells treated with 6-OHDA or overexpressed α-synuclein. Cleaved caspase-3 levels significantly increased in cells treated with 6-OHDA or overexpressed α-synuclein. 6-OHDA or α-synuclein overexpression that induced cleaved caspase-3 levels to increase was reduced by MANF treatment. In addition, MANF treatment upregulated GRP78 expressions in cells treated with 6-OHDA or overexpressed α-synuclein, and RNAi knockdown for GRP78 could block the MANF induced cell survival from 6-OHDA treatment. Furthermore, GRP78 overexpression inhibited 6-OHDA-induced apoptosis. Our data suggest that MANF inhibits apoptosis induced by 6-OHDA and overexpressed α-synuclein in SH-SY5Y cells via upregulating GRP78 in the transcriptional pattern. PMID:27145383

  18. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  19. Salicin from Willow Bark can Modulate Neurite Outgrowth in Human Neuroblastoma SH-SY5Y Cells.

    PubMed

    Wölfle, Ute; Haarhaus, Birgit; Kersten, Astrid; Fiebich, Bernd; Hug, Martin J; Schempp, Christoph M

    2015-10-01

    Salicin from willow bark has been used throughout centuries in China and Europe for the treatment of pain, headache, and inflammatory conditions. Recently, it could be demonstrated that salicin binds and activates the bitter taste receptor TAS2R16. Studies on rodent tissues showed the general expression of bitter taste receptors (TAS2Rs) in rodent brain. Here, we demonstrate the expression of hTAS2R16 in human neuronal tissues and the neuroblastoma cell line SH-SY5Y. The functionality was analyzed in the neuroblastoma cell line SH-SY5Y after stimulation with salicin, a known TAS2R16 agonist. In this setting salicin induced in SH-SY5Y cells phosphorylation of ERK and CREB, the key transcription factor of neuronal differentiation. PD98059, an inhibitor of the ERK pathway, as well as probenecid, a TAS2R16 antagonist, inhibited receptor phosphorylation as well as neurite outgrowth. These data show that salicin might modulate neurite outgrowth by bitter taste receptor activation. PMID:26096905

  20. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

    PubMed Central

    2012-01-01

    Background Two active compounds, baicalein and its glycoside baicalin were found in the dried root of Scutellaria baicalensis Georgi, and reported to be neuroprotective in vitro and in vivo. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism. Methods Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots. Results Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2. Conclusion The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells. PMID:22264378

  1. Curcumin Attenuated Bupivacaine-Induced Neurotoxicity in SH-SY5Y Cells Via Activation of the Akt Signaling Pathway.

    PubMed

    Fan, You-Ling; Li, Heng-Chang; Zhao, Wei; Peng, Hui-Hua; Huang, Fang; Jiang, Wei-Hang; Xu, Shi-Yuan

    2016-09-01

    Bupivacaine is widely used for regional anesthesia, spinal anesthesia, and pain management. However, bupivacaine could cause neuronal injury. Curcumin, a low molecular weight polyphenol, has a variety of bioactivities and may exert neuroprotective effects against damage induced by some stimuli. In the present study, we tested whether curcumin could attenuate bupivacaine-induced neurotoxicity in SH-SY5Y cells. Cell injury was evaluated by examining cell viability, mitochondrial damage and apoptosis. We also investigated the levels of activation of the Akt signaling pathway and the effect of Akt inhibition by triciribine on cell injury following bupivacaine and curcumin treatment. Our findings showed that the bupivacaine treatment could induce neurotoxicity. Pretreatment of the SH-SY5Y cells with curcumin significantly attenuated bupivacaine-induced neurotoxicity. Interestingly, the curcumin treatment increased the levels of Akt phosphorylation. More significantly, the pharmacological inhibition of Akt abolished the cytoprotective effect of curcumin against bupivacaine-induced cell injury. Our data suggest that pretreating SH-SY5Y cells with curcumin provides a protective effect on bupivacaine-induced neuronal injury via activation of the Akt signaling pathway. PMID:27233246

  2. PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells.

    PubMed

    Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Han, Hailong; Zhao, Mingyi; Li, Ying; Zhang, Chen; Tian, Jing; Bing, Guoying; Zhao, Lingling

    2015-08-01

    Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders. PMID:26070385

  3. Ropinirole alters gene expression profiles in SH-SY5Y cells: a whole genome microarray study

    PubMed Central

    Zhu, M.Z.; Le, W.D.; Jin, G.

    2016-01-01

    Ropinirole (ROP) is a dopamine agonist that has been used as therapy for Parkinson's disease. In the present study, we aimed to detect whether gene expression was modulated by ROP in SH-SY5Y cells. SH-SY5Y cell lines were treated with 10 µM ROP for 2 h, after which total RNA was extracted for whole genome analysis. Gene expression profiling revealed that 113 genes were differentially expressed after ROP treatment compared with control cells. Further pathway analysis revealed modulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, with prominent upregulation of PIK3C2B. Moreover, batches of regulated genes, including PIK3C2B, were found to be located on chromosome 1. These findings were validated by quantitative RT-PCR and Western blot analysis. Our study, therefore, revealed that ROP altered gene expression in SH-SY5Y cells, and future investigation of PIK3C2B and other loci on chromosome 1 may provide long-term implications for identifying novel target genes of Parkinson's disease. PMID:26785691

  4. PACAP protects against inflammatory-mediated toxicity in dopaminergic SH-SY5Y cells: implication for Parkinson's disease.

    PubMed

    Brown, Dwayne; Tamas, Andrea; Reglodi, Dora; Tizabi, Yousef

    2014-10-01

    There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson's disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown to possess neurotrophic as well as neuroprotective properties. In this study, we sought to determine whether PACAP could protect SH-SY5Y dopaminergic cells against toxicity induced by inflammatory mediators. For this purpose, THP-1 cells which possess microglia-like property were stimulated by a combination of lipopolysaccharide (LPS) and interferon gamma (IFN-γ), and the media containing inflammatory mediators were isolated and applied to SH-SY5Y cells. Such treatment resulted in approximately 54 % cell death as well as a reduction in brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-binding protein (p-CREB). Pretreatment of the SH-SY5Y cells with PACAP (1-38) dose-dependently attenuated toxicity induced by the inflammatory mediators. PACAP effects, in turn, were dose-dependently blocked by the PACAP receptor antagonist (PACAP 6-38). These results suggest protective effects of PACAP against inflammatory-induced toxicity in a cellular model of PD that is likely mediated by enhancement of cell survival markers through activation of PACAP receptors. Hence, PACAP or its agonists could be of therapeutic benefit in inflammatory-mediated PD. PMID:24740430

  5. Synthesis, crystal structure and magnetic properties of a new pillared perovskite La{sub 5}Mo{sub 2.75}V{sub 1.25}O{sub 16}

    SciTech Connect

    Ramezanipour, Farshid; Derakhshan, Shahab; Greedan, John E. Cranswick, Lachlan M.D.

    2008-12-15

    A new pillared perovskite compound La{sub 5}Mo{sub 2.76(4)}V{sub 1.25(4)}O{sub 16}, has been synthesized by solid-state reaction and its crystal structure has been characterized using powder X-ray and neutron diffraction. The magnetic properties of this compound have been investigated using SQUID magnetometry, and the magnetic structure has been studied using neutron diffraction data. A theoretical calculation of relative strengths of spin interactions among different magnetic ions and through different pathways has been performed using extended Hueckel, spin dimer analysis. The crystal structure of this material contains perovskite-type layers that are connected through edge-sharing dimeric units of octahedra. The structure is described in space group C2/m with unit cell parameters a=7.931(2) A, b=7.913(2) A, c=10.346(5) A and {beta}=95.096(5){sup o}. The material shows both short-range ferrimagnetic correlations from {approx}200 to 110 K and long-range antiferromagnetic order below T{sub c}{approx}100 K. The magnetic structure was investigated by neutron diffraction and is described by k=(0 0 1/2 ) as for other pillared perovskites. It consists of a ferrimagnetic arrangement of Mo and V within the layers that are coupled antiferromagnetically between layers. This is the first magnetic structure determination for any Mo-based pillared perovskite. - Graphical abstract: Long-range magnetic order below 100 K in the pillared perovskite La{sub 5}Mo{sub 2.75}V{sub 1.25}O{sub 16}. The magnetic structure is shown in the inset.

  6. Differential effects of α-tocopherol and N-acetyl-cysteine on advanced glycation end product-induced oxidative damage and neurite degeneration in SH-SY5Y cells.

    PubMed

    Pazdro, Robert; Burgess, John R

    2012-04-01

    Advanced glycation end products (AGEs) result from non-enzymatic glycation of proteins and cause cellular oxidative stress in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner. Due to these effects, AGEs are implicated as a causal factor in diabetic complications. Several antioxidants, including vitamin E, improve cell viability and diminish markers of oxidative damage in cells exposed to AGEs. However, vitamin E has been studied in cell culture systems with primary focus on apoptosis and lipid peroxidation, while its influences on AGE-induced protein and DNA oxidation, intracellular antioxidant status and cell morphology remain largely unknown. Here, we verify the suppression of AGE-induced cell death and lipid peroxidation by 200μM α-tocopherol in SH-SY5Y cells. We report the partial inhibition of DNA oxidation and a decrease in protein carbonyl formation by α-tocopherol with no effects on intracellular GSH concentrations. We observed that 2mM N-acetyl cysteine (NAC) also had a suppressive effect on DNA and protein oxidation, but unlike α-tocopherol, it caused a marked increase in intracellular GSH. Finally, we compared the ability of both antioxidants to maintain neurites in SH-SY5Y cells and found that α-tocopherol had no effect on neurite loss due to AGEs, while NAC fully maintained cell morphology. Thus, while α-tocopherol suppressed AGE-induced macromolecule damage, it was ineffective against neurite degeneration. These results may implicate thiol oxidation and maintenance as a major regulator of neurite degeneration in this model. PMID:22261284

  7. Changes in microstructure during primary creep of a Ti-47Al-2Nb-1Mn-0.5W-0.5Mo-0.2Si alloy

    SciTech Connect

    Seo, D.Y.; Bieler, T.R.; An, S.U.; Larsen, D.E.

    1998-01-01

    Cast gamma titanium aluminides are gaining acceptance as potential replacements for superalloy and steel components in many applications. One particular alloy with W, Mo, and Si additions has shown exceptional primary creep resistance. Quantitative microscopic comparisons were made between microstructures in undeformed and deformed regions in creep specimens deformed to strains between 0.1 and 1.5 pct strain, using optical microscope, scanning electron microscope (SEM), and transmission electron microscope (TEM) techniques. As-hot isostatically pressed (hipped) and heat-treated (1,010 C for 50 hours) conditions were compared. The as-hipped specimen had a higher lamellar volume fraction, and it crept more than 100 times faster. The lamellar spacing in the lamellar grains systematically decreased by 15 to 35%, with increasing stress, during the first 0.1 to 2% strain. Precipitates containing W, Mo, and/or Si were observed in the deformed gage and undeformed grip sections of the heat-treated specimens. Precipitation is nucleated by heat treatment, but, during creep deformation, a more homogeneous and faster growth process occurs in the gage section than in the aged but undeformed grip section. The gage section had a 35% higher precipitate volume fraction, but their average size was smaller. A lower volume fraction of lamellar grains and the presence of precipitates account for the excellent creep resistance in the heat-treated alloy.

  8. Multiple mechanisms of iron-induced amyloid beta-peptide accumulation in SHSY5Y cells: protective action of negletein.

    PubMed

    Banerjee, Priyanjalee; Sahoo, Arghyadip; Anand, Shruti; Ganguly, Anirban; Righi, Giuliana; Bovicelli, Paolo; Saso, Luciano; Chakrabarti, Sasanka

    2014-12-01

    The increased accumulation of iron in the brain in Alzheimer's disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of negletein, which should be explored in suitable animal models of AD. PMID:25249289

  9. Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells.

    PubMed

    Seçme, Mücahit; Eroğlu, Canan; Dodurga, Yavuz; Bağcı, Gülseren

    2016-07-01

    Neuroblastoma is one of the most common types of pediatric tumors that can spread quickly in neuronal tissues. Oleuropein which is active compound of olive leaves, belongs to polyphenols group and has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the study is to determine the therapeutic effects of oleuropein on cell proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of oleuropein on cell viability was determined by XTT method. 84 cell cycle control and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on apoptosis were researched by TUNEL assay. Protein expressions were determined by western blot analysis. Effects of oleuropein on cell invasion, colony formation and migration were detected by matrigel-chamber, colony formation assay and wound-healing assay, respectively. IC50 value of oleuropein in SH-SY5Y cells was detected as 350μM at 48th hours. It is determined that oleuropein causes cell cycle arrest by down-regulating of CylinD1,CylinD2,CyclinD3,CDK4,CDK6 and up-regulating of p53 and CDKN2A, CDKN2B, CDKN1A gene expressions. Oleuropein also induces apoptosis by inhibiting of Bcl-2 and activating of Bax,caspase-9 and caspase-3 gene expressions. Apoptotic cell ratio was found 36.4±3.27% in oleuropein dose group. Oleuropein decreased invasion in SH-SY5Y cells and suppressed colony numbers in ratio of 53.6±4.71%.Our results demonstrated that oleuropein can be a therapeutic agent in the treatment of neuroblastoma. PMID:27032461

  10. Plasma-activated medium-induced intracellular zinc liberation causes death of SH-SY5Y cells.

    PubMed

    Hara, Hirokazu; Taniguchi, Miko; Kobayashi, Mari; Kamiya, Tetsuro; Adachi, Tetsuo

    2015-10-15

    Plasma is an ionized gas consisting of ions, electrons, free radicals, neutral particles, and photons. Plasma-activated medium (PAM), which is prepared by the irradiation of cell-free medium with non-thermal atmospheric pressure plasma, induces cell death in various types of cancer cell. Since PAM contains reactive oxygen species (ROS), its anti-cancer effects are thought to be attributable to oxidative stress. Meanwhile, oxidative stress has been shown to induce the liberation of zinc (Zn(2+)) from intracellular Zn(2+) stores and to provoke Zn(2+)-dependent cell death. In this study, we thus examined whether Zn(2+) is involved in PAM-induced cell death using human neuroblastoma SH-SY5Y cells. Exposure to PAM triggered cell death in SH-SY5Y cells. The cell-permeable Zn(2+) chelator N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) protected against PAM-induced cell death. Zn(2+) imaging using the fluorescent Zn(2+) probe FluoZin-3 revealed that PAM elicited a rise of intracellular free Zn(2+). In addition, PAM stimulated PARP-1 activation, mitochondrial ROS generation, and the depletion of intracellular NAD(+) and ATP. These findings suggest that PAM-induced PARP-1 activation causes energy supply exhaustion. Moreover, TPEN suppressed all of these events elicited by PAM. Taken together, we demonstrated here that Zn(2+) released from intracellular Zn(2+) stores serves as a key mediator of PAM-induced cell death in SH-SY5Y cells. PMID:26319292

  11. Neuroprotective role of sphingosine-1-phosphate in L-BMAA treated neuroblastoma cells (SH-SY5Y).

    PubMed

    Muñoz-Sáez, Emma; de Munck García, Estefanía; Arahuetes Portero, Rosa María; Vicente, Francisca; Ortiz-López, Francisco Javier; Cantizani, Juan; Gómez Miguel, Begoña

    2015-04-23

    Sphingosine-1-phosphate (S1P) is a bioactive lipid which regulates proliferation, cell migration, survival and differentiation by specific receptors activation. We studied its effects on L-BMAA treated neuroblastoma cells (SH-SY5Y), an amino acid that can trigger neurodegenerative diseases such as amyotrophic lateral sclerosis/Parkinson dementia complex (ALS/PDC). We found that S1P protects from necrosis and prevents the GSK3 increasing as long as the PI3K/AKT pathway is active. Moreover, GSK3 inhibition protects against neuronal death caused by L-BMAA. PMID:25769802

  12. Proton conduction and chemical stability of (La{sub 0.5}Sr{sub 0.5})(Mg{sub 0.5+y}Nb{sub 0.5-y})O{sub 3-{delta}}

    SciTech Connect

    Kawasaki, Yuya; Okada, Sachio; Ito, Naoki; Matsumoto, Hiroshige Ishihara, Tatsumi

    2009-02-04

    Electrical conduction properties of complex perovskite-type oxides in the (La{sub 0.5}Sr{sub 0.5})(Mg{sub 0.5+y}Nb{sub 0.5-y})O{sub 3-{delta}} (y = 0.02-0.06) series at intermediate-high temperatures were investigated; introduction of protons by hydration of oxide-ion vacancies was expected by increasing the Mg/Nb ratio from unity. The conductivity depended on y and a maximum conductivity was obtained at y = 0.04: {sigma} = 4.9 x 10{sup -6} S cm{sup -1} at 400 deg. C in wet H{sub 2} atmospheres. From electromotive force measurements of hydrogen and water vapor concentration cells, electrical conduction in wet H{sub 2} atmospheres can be attributed to ionic conduction, and proton conduction is dominant below 700 deg. C. Unlike other perovskite-type proton conductors, (La{sub 0.5}Sr{sub 0.5})(Mg{sub 0.54}Nb{sub 0.46})O{sub 3-{delta}} was stable in CO{sub 2} atmospheres even in the low-intermediate temperature region due to dilution of reactive strontium by lanthanum.

  13. Lactoferrin and ovotransferrin contribute toward antioxidative effects of Edible Bird's Nest against hydrogen peroxide-induced oxidative stress in human SH-SY5Y cells.

    PubMed

    Hou, Zhiping; Imam, Mustapha Umar; Ismail, Maznah; Azmi, Nur Hanisah; Ismail, Norsharina; Ideris, Aini; Mahmud, Rozi

    2015-01-01

    There are reports of improved redox outcomes due to consumption of Edible Bird's Nest (EBN). Many of the functional effects of EBN can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of aging and its related diseases like Alzheimer's disease. In this study, the antioxidative potentials of EBN and its constituents, lactoferrin (LF) and ovotransferrin (OVF), were determined and protective effects against hydrogen peroxide (H2O2)- induced toxicity on SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange and propidium iodide (AO/PI) staining with microscopy were examined. Results showed that EBN and its constituents attenuated H2O2-induced cytotoxicity, and decreased radical oxygen species (ROS) through increased scavenging activity. Furthermore, LF, OVF, and EBN produced transcriptional changes in antioxidant related genes that tended towards neuroprotection as compared to H2O2-treated group. Overall, the results suggest that LF and OVF may produce synergistic or all-or-none antioxidative effects in EBN. PMID:26057702

  14. Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity.

    PubMed

    Ansari, Mubeen A; Keller, Jeffrey N; Scheff, Stephen W

    2008-12-01

    Oxidative stress is one of the hypotheses involved in the etiology of Alzheimer's disease (AD). Considerable attention has been focused on increasing the intracellular glutathione (GSH) levels in many neurodegenerative diseases, including AD. Pycnogenol (PYC) has antioxidant properties and stabilizes intracellular antioxidant defense systems including glutathione levels. The present study investigated the protective effects of PYC on acrolein-induced oxidative cell toxicity in cultured SH-SY5Y neuroblastoma cells. Decreased cell survival in SH-SY5Y cultures treated with acrolein correlated with oxidative stress, increased NADPH oxidase activity, free radical production, protein oxidation/nitration (protein carbonyl, 3-nitrotyrosine), and lipid peroxidation (4-hydroxy-2-nonenal). Pretreatment with PYC significantly attenuated acrolein-induced cytotoxicity, protein damage, lipid peroxidation, and cell death. A dose-response study suggested that PYC showed protective effects against acrolein toxicity by modulating oxidative stress and increasing GSH. These findings provide support that PYC may provide a promising approach for the treatment of oxidative stress-related neurodegenerative diseases such as AD. PMID:18822368

  15. Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells.

    PubMed

    Wang, Yan; Hilton, Benjamin A; Cui, Kui; Zhu, Meng-Yang

    2015-08-01

    DNA damage is a form of cell stress and injury. Increased systemic DNA damage is related to the pathogenic development of neurodegenerative diseases. Depression occurs in a relatively high percentage of patients suffering from degenerative diseases, for whom antidepressants are often used to relieve depressive symptoms. However, few studies have attempted to elucidate why different groups of antidepressants have similar effects on relieving symptoms of depression. Previously, we demonstrated that neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)- and camptothecin (CPT) induced the DNA damage response in SH-SY5Y cells, and DSP4 caused cell cycle arrest which was predominately in the S-phase. The present study shows that CPT treatment also resulted in similar cell cycle arrest. Some classic antidepressants could reduce the DNA damage response induced by DSP4 or CPT in SH-SY5Y cells. Cell viability examination demonstrated that both DSP4 and CPT caused cell death, which was prevented by spontaneous administration of some tested antidepressants. Flow cytometric analysis demonstrated that a majority of the tested antidepressants protect cells from being arrested in S-phase. These results suggest that blocking the DNA damage response may be an important pharmacologic characteristic of antidepressants. Exploring the underlying mechanisms may allow for advances in the effort to improve therapeutic strategies for depression appearing in degenerative and psychiatric diseases. PMID:26038195

  16. BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation

    PubMed Central

    Goldie, Belinda J.; Barnett, Michelle M.; Cairns, Murray J.

    2014-01-01

    The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialized features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterize the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas et al. (2000) using integrative whole-genome gene and microRNA (miRNA) expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modeled. PMID:25360083

  17. Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells

    PubMed Central

    Li, Le; Zhang, Qing-guo; Lai, Lu-ying; Wen, Xian-jie; Zheng, Ting; Cheung, Chi-wai; Zhou, Shu-qin; Xu, Shi-yuan

    2013-01-01

    Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property. PMID:24228138

  18. Neurotoxicity effects of atrazine-induced SH-SY5Y human dopaminergic neuroblastoma cells via microglial activation.

    PubMed

    Ma, Kun; Wu, Hao-Yu; Zhang, Bo; He, Xi; Li, Bai-Xiang

    2015-11-01

    Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is a broad-spectrum herbicide with a wide range of applications worldwide. However, ATR is neurotoxic; it reduces dopamine levels in the substantia nigra and corpus striatum in the midbrain, affects the absorption of synaptic vesicles and synaptic bodies, and interferes with dopamine storage and uptake in synaptic vesicles, leading to neurodegenerative disorders. Microglia are resident immunocompetent and phagocytic cells that regulate and participate in the microenvironment in the central nervous system. They demonstrate macrophage characteristics after activation by releasing inflammatory cytokines and neurotoxic substances to increase the inflammatory response, and are thus involved in neurodegeneration. The aim of this study was to investigate the neurotoxic effects of ATR-activated microglia-mediated neuronal damage in terms of human dopaminergic neuroblastoma SH-SY5Y cell death. ATR was administered to BV-2 microglial cells at 12.5, 25, and 50 μM for 1, 6, 12, 24 and 48 h, respectively. ATR increased activated-microglia-induced overexpression of reactive oxygen species, inducible nitric oxide synthase, nitric oxide, gp91(phox), p47(phox), and the inflammatory cytokines tumor necrosis factor α and interleukin-1β, thus reducing SH-SY5Y cell viability. These results suggest that activated microglia may play a critical role in inflammation-mediated dopaminergic neuronal death, and provide the basis for further studies on the mechanisms of ATR-induced dopaminergic system toxicity. PMID:26256823

  19. Effect of graphene oxide on undifferentiated and retinoic acid-differentiated SH-SY5Y cells line

    NASA Astrophysics Data System (ADS)

    Lv, Min; Zhang, Yujie; Liang, Le; Wei, Min; Hu, Wenbing; Li, Xiaoming; Huang, Qing

    2012-06-01

    Graphene oxide (GO), has created an unprecedented opportunity for development and application in biology, due to its abundant functional groups and well water solubility. Recently, the potential toxicity of GO in the environment and in humans has garnered more and more attention. In this paper, we systematically studied the cytotoxicity of GO nanosheets via examining the effect of GO on the morphology, viability and differentiation of a human neuroblastoma SH-SY5Y cell line, which was an ideal model used to study neuronal disease in vitro. The results suggested that GO had no obvious cytotoxicity at low concentration (<80 μg mL-1) for 96 h, but the viability of cells exhibited dose- and time-dependent decreases at high concentration (>=80 μg mL-1). Moreover, GO did not induce apoptosis. Very interestingly, GO significantly enhanced the differentiation of SH-SY5Y induced-retinoic acid (RA) by evaluating neurite length and the expression of neuronal marker MAP2. These data provide a promising application for neurodegenerative diseases.

  20. Antipsychotic drugs increase N-acetylaspartate and N-acetylaspartylglutamate in SH-SY5Y human neuroblastoma cells.

    PubMed

    Arun, Peethambaran; Madhavarao, Chikkathur N; Moffett, John R; Namboodiri, Aryan M A

    2008-08-01

    N-Acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) are related neuronal metabolites associated with the diagnosis and treatment of schizophrenia. NAA is a valuable marker of neuronal viability in magnetic resonance spectroscopy, a technique which has consistently shown NAA levels to be modestly decreased in the brains of schizophrenia patients. However, there are conflicting reports on the changes in brain NAA levels after treatment with antipsychotic drugs, which exert their therapeutic effects in part by blocking dopamine D(2) receptors. NAAG is reported to be an agonist of the metabotropic glutamate 2/3 receptor, which is linked to neurotransmitter release modulation, including glutamate release. Alterations in NAAG metabolism have been implicated in the development of schizophrenia possibly via dysregulation of glutamate neurotransmission. In the present study we have used high performance liquid chromatography to determine the effects of the antipsychotic drugs haloperidol and clozapine on NAA and NAAG levels in SH-SY5Y human neuroblastoma cells, a model system used to test the responses of dopaminergic neurons in vitro. The results indicate that the antipsychotic drugs haloperidol and clozapine increase both NAA and NAAG levels in SH-SY5Y cells in a dose and time dependant manner, providing evidence that NAA and NAAG metabolism in neurons is responsive to antipsychotic drug treatment. PMID:18631215

  1. Riluzole decreases synthesis of N-acetylaspartate and N-acetylaspartylglutamate in SH-SY5Y human neuroblastoma cells.

    PubMed

    Arun, Peethambaran; Moffett, John R; Namboodiri, Aryan M A

    2010-06-01

    N-acetylaspartate (NAA) is present at very high concentrations in the brain and is used as a non-invasive marker of neuronal viability in magnetic resonance spectroscopy. N-acetylaspartylglutamate (NAAG) is an acetylated dipeptide formed from NAA, and may be an agonist of the mGluR3 receptor. Both NAA and NAAG are synthesized primarily in neurons. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder resulting in motor neuron death, and progressive paralysis. Levels of both NAA and NAAG are reported to be decreased in ALS. Riluzole is a glutamatergic modulating agent used to treat ALS, but there are conflicting results in the literature concerning the recovery of NAA after riluzole treatment. We studied the effects of riluzole on the biosynthesis of both NAA and NAAG in SH-SY5Y human neuroblastoma cells. We used two methodologies to examine the effect; one involving radiolabel incorporation from corresponding substrates into NAA and NAAG, and the other involving the measurement of endogenous NAA and NAAG levels using HPLC. We show that riluzole treatment, which decreases glutamatergic neuronal excitation, decreases the synthesis and levels of both NAA and NAAG in SH-SY5Y cells in a dose and time dependant manner. These results suggest that the synthesis of NAA and NAAG may be coupled to glutamatergic neurotransmission, and further investigations along these lines are warranted. PMID:20394738

  2. Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells.

    PubMed

    Das, Jharna R; Tizabi, Yousef

    2009-10-01

    Although the etiology of Parkinson's disease (PD) remains elusive, a number of toxins including elevated salsolinol, an endogenous metabolite of dopamine may contribute to its pathology. It was reported recently that nicotine may have protective effects against salsolinol-induced toxicity in human neuroblastoma derived SH-SY5Y cells and that these effects of nicotine are mediated by nicotinic receptors. Donepezil (Aricept) is a reversible non-competitive acetylcholinesterase inhibitor that is approved for use in mild to moderate Alzheimer's disease. The increase in acetylcholine concentrations is believed to be the major contributory factor in donepezil's therapeutic efficacy. However, cholinesterase inhibitors may also directly interact with nicotinic receptors and possess neuroprotective properties. In this study, we sought to determine whether donepezil may have protective effects against salsolinol-induced toxicity in SH-SY5Y cells and whether the combination of donepezil and nicotine may result in additive protection. Moreover, it was of interest to elucidate the role of nicotinic receptors as well as cell cycle and apoptosis in mechanism of action of these compounds. SH-SY5Y cells were exposed to 0.6 mM salsolinol with and without various drug pretreatments for 48 h. Nicotine (50 muM) resulted in approximately 54% protection and donepezil (5 muM) resulted in approximately 40% protection, and the combination of the two resulted in an additive (approximately 93%) protection against salsolinol-induced toxicity. Salsolinol caused an arrest of the cells in G(1)-phase of cell cycle and an increase in apoptotic indices that were blocked by the combination of donepezil and nicotine. Mecamylamine, a non-selective nicotinic receptor antagonist completely blocked the effects of nicotine and partially attenuated the effects of donepezil. A combination of atropine, a muscarinic receptor antagonist and mecamylamine completely blocked the effects of donepezil, indicating

  3. NGF sensitizes TrkA SH-SY5Y neuroblastoma cells to TRAIL-induced apoptosis

    PubMed Central

    Ruggeri, P; Cappabianca, L; Farina, A R; Gneo, L; Mackay, A R

    2016-01-01

    We report a novel pro-apoptotic function for nerve growth factor (NGF) and its tropomyosin-related kinase A (TrkA) receptor in sensitizing TRAIL (TNF-related apoptotis-inducing ligand)-resistant SH-SY5Y neuroblastoma (NB) cells to TRAIL-induced apoptosis, resulting in the abrogation of anchorage-independent tumourigenic growth in vitro. We show that the TRAIL-resistant SH-SY5Y phenotype is cFLIP (cellular FLICE-like inhibitory protein) dependent and not due to low-level functional TRAIL receptor or caspase expression or an inhibitory equilibrium between functional and decoy TRAIL receptors or B-cell lymphoma 2 (Bcl-2) and BH3-only (Bcl-2 homology domain 3-only) family proteins. NGF sensitization of SH-SY5Y cells to TRAIL-induced apoptosis was dependent upon TrkA expression, activation and subsequent sequestration of cFLIP. This reduces cFLIP recruitment to TRAIL-activated death receptors and increases the recruitment of caspase-8, leading to TRAIL-induced, caspase-dependent, type II apoptosis via the intrinsic mitochondrial pathway. This effect was temporary, inhibited within 6 h by nuclear factor-κ binding (NF-κB)-mediated increase in myeloid cell leukaemia-1 (Mcl-1) expression, abrogated by transient cFLIP or B-cell lymphoma-extra large (Bcl-xL) overexpression and optimized by NF-κB and Mcl-1 inhibitors. This novel mechanism adds an important pro-apoptotic immunological dimension to NGF/TrkA interaction that may not only help to explain the association between TrkA expression, better prognosis and spontaneous remission in NB, but also provides a novel potential pro-apoptotic therapeutic use for NGF, TRAIL and inhibitors of NF-κB and/or Mcl-1 in favourable and unfavourable NBs that express TrkA and exhibit cFLIP-mediated TRAIL resistance. PMID:27551499

  4. Synthesis and electrochemical characterization of Sr2Fe1.5Mo0.5O6-Sm0.2Ce0.8O1.9 composite cathode for intermediate-temperature solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Dai, Ningning; Lou, Zhongliang; Wang, Zhenhua; Liu, Xiaoxi; Yan, Yiming; Qiao, Jinshuo; Jiang, Taizhi; Sun, Kening

    2013-12-01

    Nanoporous composite oxides Sr2Fe1.5Mo0.5O6-Sm0.2Ce0.8O1.9 (SFM-SDC) have been prepared by a facile one-step method as cathode for intermediate-temperature solid oxide fuel cells (IT-SOFCs). The SFM-SDC composite materials have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM) and electrochemical impedance spectroscopy (EIS). The EIS results exhibit that SFM-SDC40 (wt% 60:40) cathode has encouraging electrochemical performance with low polarization resistance (Rp) on YSZ (Y2O3-stabilized ZrO2) electrolyte. Subsequently, bi-layer cathodes SDC/SFM-SDC are fabricated, and excellent electrochemical performance of such composite cathodes are observed. We demonstrate that the SDC interlayer significantly decreases the Rp of cathode and accelerates the charge transfer process. As a result, the Rp of the SDC/SFM-SDC40 bi-layer cathodes is almost 50% less than that of SFM-SDC40 cathode on YSZ electrolyte at 800 °C, and Rp is only 0.11 Ω cm2. Compared with single cells without an interlayer, the anode-supported single cells with SDC interlayer exhibit enhancement in overall power performance.

  5. Irradiation creep of 11Cr-0.5Mo-2W,V,Nb ferritic-martensitic, modified 316, and 15Cr-20Ni austenitic S.S. irradiated in FFTF to 103-206 dpa

    NASA Astrophysics Data System (ADS)

    Uehira, A.; Mizuta, S.; Ukai, S.; Puigh, R. J.

    2000-12-01

    The irradiation creep of 11Cr-0.5Mo-2W-0.2V-0.05Nb ferritic-martensitic (PNC-FMS), modified 316 (PNC316) and 15Cr-20Ni base austenitic S.S. were determined by the gas pressurized capsule irradiation test using MOTA in FFTF. The pressurized capsules and open tubes were irradiated at 678-943 K to a peak dose of 206 dpa. The irradiation creep coefficients were derived from the diametral change differences between the capsules and open tubes, accounting for the stress-induced swelling. The creep compliance B0 and creep-swelling coupling coefficient D for PNC-FMS were found to be 0.43-0.76×10-6 MPa-1 dpa-1 and 0.85-2.5×10-2 MPa-1 for volumetric swelling, respectively. For both PNC316 and 15Cr-20Ni base S.S. the irradiation creep properties were very similar. B0 and D range from 0.55 to -1.5×10-6 MPa-1 dpa-1 and from 1.2 to -2.8×10-3 MPa-1, respectively.

  6. The characteristic of strontium-site deficient perovskites SrxFe1.5Mo0.5O6-δ (x = 1.9-2.0) as intermediate-temperature solid oxide fuel cell cathodes

    NASA Astrophysics Data System (ADS)

    Yang, Guoquan; Feng, Jie; Sun, Wang; Dai, Ningning; Hou, Mingyue; Hao, Xiaoming; Qiao, Jinshuo; Sun, Kening

    2014-12-01

    As the cathodes for intermediate-temperature solid oxide fuel cells (IT-SOFCs), A-site deficient SrxFe1.5Mo0.5O6-δ (x = 1.9-2.0) (SxFM) materials have been successfully synthesized using the sol-gel combustion method. In the perovskite structure of these oxides, the unit cell varies from pseudocubic to cubic with increasing deficiency. Thermal expansion coefficient of SxFM has also been measured and compared with that of Scandium-stabilized zirconium (ScSZ) electrolyte. X-ray photoelectron spectroscopy (XPS) results indicate that the Sr-deficiency has changed the proportion of Fe2+/Fe3+ and Mo6+/Mo5+ ratios, which directly influences the conductivity of SxFM materials. S1.950FM possesses the largest electrical conductivity and the lowest polarization resistance (Rp) among all the samples. The maximum power densities of a single cell with the S1.950FM cathode reaches 1083 mW cm-2, and the area specific resistance value is 0.17 Ω cm2 at 800 °C. These results indicate that the A-site deficiency could promote the electrochemical performance of SFM materials as cathodes for IT-SOFCs.

  7. Theoretical investigation of H2 oxidation on the Sr2Fe(1.5)Mo(0.5)O6 (001) perovskite surface under anodic solid oxide fuel cell conditions.

    PubMed

    Suthirakun, Suwit; Ammal, Salai Cheettu; Muñoz-García, Ana B; Xiao, Guoliang; Chen, Fanglin; zur Loye, Hans-Conrad; Carter, Emily A; Heyden, Andreas

    2014-06-11

    Periodic density functional theory (DFT) calculations and microkinetic modeling are used to investigate the electrochemical oxidation of H2 fuel on the (001) surface of Sr2Fe1.5Mo0.5O6 (SFMO) perovskite under anodic solid oxide fuel cell conditions. Three surface models with different Fe/Mo ratios in the topmost layer-identified by ab initio thermodynamic analysis-are used to investigate the H2 oxidation mechanism. A microkinetic analysis that considers the effects of anode bias potential suggests that a higher Mo concentration in the surface increases the activity of the surface toward H2 oxidation. At operating voltage and anodic SOFC conditions, the model predicts that water desorption is rate-controlling and that stabilizing the oxygen vacancy structure increases the overall rate for H2 oxidation. Although we find that Mo plays a crucial role in improving catalytic activity of SFMO, under fuel cell operating conditions, the Mo content in the surface layer tends to be very low. On the basis of these results and in agreement with previous experimental observations, a strategy for improving the overall electrochemical performance of SFMO is increasing the Mo content or adding small amounts of an active transition metal, such as Ni, to the surface to lower the oxygen vacancy formation energy of the SFMO surface. PMID:24826843

  8. Raman micro-spectroscopy study of living SH-SY5Y cells adhering on different substrates.

    PubMed

    Caponi, S; Mattana, S; Ricci, M; Sagini, K; Urbanelli, L; Sassi, P; Morresi, A; Emiliani, C; Dalla Serra, M; Iannotta, S; Musio, C; Fioretto, D

    2016-01-01

    In this paper we test the ability of Raman micro-spectroscopy and Raman mapping to investigate the status of cells grown in adhesion on different substrates. The spectra of immortalized SH-SY5Y cells, grown on silicon and on metallic substrates are compared with those obtained for the same type of cells adhering on organic polyaniline (PANI), a memristive substrate chosen to achieve a living bio-hybrid system. Raman spectra give information on the status of the single cell, its local biochemical composition, and on the modifications induced by the substrate interaction. The good agreement between Raman spectra collected from cells adhering on different substrates confirms that the PANI, besides allowing the cell growth, doesn't strongly affect the general biochemical properties of the cell. The investigation of the cellular state in a label free condition is challenging and the obtained results confirm the Raman ability to achieve this information. PMID:26256426

  9. Diode pumped Nd:Lu0.5Y0.5VO4-LBO red laser at 671 nm

    NASA Astrophysics Data System (ADS)

    Li, Y. L.; Liu, J. Y.; Zhang, Y. C.

    2012-03-01

    We report a efficient compact red laser at 671 nm generation by intracavity frequency doubling of a continuous wave laser operation of a diode pumped Nd:Lu0.5Y0.5VO4 laser on the 4 F 3/2-4 I 13/2 transition at 1342 nm. An LBO crystal, cut for critical type I phase matching at room temperature is used for second harmonic generation of the laser. At an absorbed pump power of 17.8 W, as high as 2.25 W of continuous wave output power at 671 nm is achieved with 10-mm-long LBO. The optical-to-optical conversion efficiency is up to 12.6%, and the fluctuation of the red output power was better than 3.6% in the given 30 min.

  10. Insulin exerts neuroprotective effects via Akt/Bcl-2 signaling pathways in differentiated SH-SY5Y cells.

    PubMed

    Ramalingam, Mahesh; Kim, Sung-Jin

    2015-02-01

    In the present study, the changes in the cell viability at different concentrations of hydrogen peroxide (H2O2) for 3 h used to establish a model of oxidative stress. Further assays with 200 μM H2O2 induces significant changes in the levels of lactate dehydrogenase (LDH), nitric oxide (NO), reactive oxygen species (ROS) and calcium ion (Ca(2+)) in neuronal cells, but insulin can effectively diminish the oxidative damages. Moreover, cells treated with insulin increased the H2O2-induced suppression of glutathione levels and exerted an apparent suppressive effect on oxidative products. The results of Akt, Bcl-2, Bax, IRβ, IGF-1Rβ, IRS-1 and IRS-2 showed that insulin treatment had a protective effect on H2O2-induced oxidative stress in RA-differentiated SH-SY5Y neuroblastoma cells. PMID:24849496

  11. Angelica polymorpha Maxim Induces Apoptosis of Human SH-SY5Y Neuroblastoma Cells by Regulating an Intrinsic Caspase Pathway.

    PubMed

    Rahman, Md Ataur; Bishayee, Kausik; Huh, Sung-Oh

    2016-02-01

    Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-3β activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy. PMID:26674967

  12. Angelica polymorpha Maxim Induces Apoptosis of Human SH-SY5Y Neuroblastoma Cells by Regulating an Intrinsic Caspase Pathway

    PubMed Central

    Rahman, Md. Ataur; Bishayee, Kausik; Huh, Sung-Oh

    2016-01-01

    Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-3β activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy. PMID:26674967

  13. Particulate matter cytotoxicity in cultured SH-SY5Y cells is modulated by simvastatin: Toxicological assessment for oxidative damage.

    PubMed

    Ferraro, S A; Astort, F; Yakisich, J S; Tasat, D R

    2016-03-01

    Epidemiological studies have shown a positive correlation between environmental particulate matter and adverse health effects. In particular, residual oil fly ash (ROFA) induces inflammation and reactive oxygen species (ROS), exerting not only local, but also systemic adverse effects. Previously, in an experimental animal model, we found that simvastatin (Sv) pretreatment was effective in preventing ROFA induced lung inflammation. Herein, using the human neuroblastoma SH-SY5Y cell line as a neurotoxicity in vitro model, we studied the potential Sv protective effect on ROFA cytotoxicity. We evaluated cell viability by the MTT assay, superoxide anion generation by NBT test, Nrf2 activation by immunofluorescence, apoptosis by cleaved-PARP and active-caspase 3 expressions, and senescence by β-galactosidase activity. SH-SY5Y cells exposed to ROFA (10 and 50μg/ml) for 24h showed decreased cell viability, increased superoxide anion generation, apoptosis and senescence. Pretreatment with Sv (1μM) for 6 days, restored cell viability to basal levels, reduced ROFA-induced O2(-) generation as well as the number of apoptotic and senescent cells. Sv pretreatment stimulated the basal and ROFA-induced levels of Nrf2 nuclear translocation suggesting that activation of the cellular antioxidant defense system prevented particle-induced oxidative stress. In parallel, rescue experiments with mevalonate did not modify the effects of SV pretreatment in any of the parameters evaluated in this study. We conclude that simvastatin may provide neuroprotection against air particulate matter-induced neurotoxicity independently of its ability to inhibit cholesterol synthesis. PMID:26773838

  14. Mu-opioids activate phospholipase C in SH-SY5Y human neuroblastoma cells via calcium-channel opening.

    PubMed

    Smart, D; Smith, G; Lambert, D G

    1995-01-15

    We have recently reported that, in SH-SY5Y cells, mu-opioid receptor occupancy activates phospholipase C via a pertussis toxin-sensitive G-protein. In the present study we have further characterized the mechanisms involved in this process. Fentanyl (0.1 microM) caused a monophasic increase in inositol 1,4,5-trisphosphate mass formation, with a peak (20.5 +/- 3.6 pmol/mg of protein) at 15 s. Incubation in Ca(2+)-free buffer abolished this response, while Ca2+ replacement 1 min later restored the stimulation of inositol 1,4,5-trisphosphate formation (20.1 +/- 0.6 pmol/mg of protein). In addition, nifedipine (1 nM-0.1 mM), an L-type Ca(2+)-channel antagonist, caused a dose-dependent inhibition of inositol 1,4,5-trisphosphate formation, with an IC50 of 60.3 +/- 1.1 nM. Elevation of endogenous beta/gamma subunits by selective activation of delta-opioid and alpha 2 adrenoceptors failed to stimulate phospholipase C. Fentanyl also caused a dose-dependent (EC50 of 16.2 +/- 1.0 nM), additive enhancement of carbachol-induced inositol 1,4,5-trisphosphate formation. In summary, we have demonstrated that in SH-SY5Y cells activation of the mu-opioid receptor allows Ca2+ influx to activate phospholipase C. However, the possible role of this mechanism in the process of analgesia remains to be elucidated. PMID:7832776

  15. Dynamin-related protein 1 mediates mitochondria-dependent apoptosis in chlorpyrifos-treated SH-SY5Y cells.

    PubMed

    Park, Jae Hyeon; Ko, Juyeon; Hwang, Jungwook; Koh, Hyun Chul

    2015-12-01

    Recent studies have demonstrated that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, mediates mitochondria-dependent apoptosis through mitochondrial division. However, little is known about the mechanism by which Drp1 modulates apoptosis in response to chlorpyrifos (CPF)-induced toxicity. In this study, we determined that CPF-induced mitochondrial apoptosis is mediated by Drp1 translocation in SH-SY5Y human neuroblastoma cells. Our results showed that CPF treatment induced intrinsic apoptosis by activating caspase-9, caspase-3, and cytochrome c release in SH-SY5Y cells. Cytosolic Drp1 translocated to the mitochondria in CPF-treated cells and was phosphorylated at Ser616. Treating cells with CPF induced the generation of reactive oxygen species (ROS) and activation of mitogen-activated protein kinases (MAPKs). Inhibiting this ROS generation and MAPK activation abolished CPF-induced expression of phospho-Drp1. Furthermore, Drp1 was required for p53 to translocate to the mitochondria under CPF-induced oxidative stress. Treating cells with mitochondrial-division inhibitor-1 (mdivi-1), which blocks Drp1 translocation, increased the viability of CPF-treated cells by abrogating Drp1 translocation and caspase-3 activation. Specifically, pretreating cells with mdivi-1 inhibited Bax translocation to the mitochondria by blocking p53 signaling. Taken together, these data reveal a novel mechanism by which Drp1 activates mitochondrial-dependent apoptosis and indicate that inhibiting Dpr1 function can protect against CPF-induced cytotoxicity. We propose that inhibiting Drp1 is a possible therapeutic approach for pesticide-induced toxicity when hyperactivated Drp1 contributes to pathology. PMID:26598294

  16. β-adrenoceptor blockers protect against staurosporine-induced apoptosis in SH-SY5Y neuroblastoma cells

    PubMed Central

    Mikami, Maya; Goubaeva, Farida; Song, Joseph H.; Lee, H.T.; Yang, Jay

    2008-01-01

    The β-adrenoceptor blockers exhibit a well-characterized anti-apoptotic property in the heart and kidney while less is known about the effect of this class of drugs on neuronal apoptosis. We studied the effects of three β- adrenoceptor blockers propranolol (1-(isoproplyamino)-3-(naphthalene-1-yloxy)propan-2-ol), atenolol (2-[4-[2-hydroxy-3-(1-methylethylamino)propoxyl]phenyl]ehanamide), and ICI 118551 (1-[2,3-(dihydro-7-methyl-1H-iden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), against staurosporine-induced apoptosis in SH-SY5Y human neuroblastoma cells. Staurosporine increased caspase 3-like activity, DNA fragmentation, PARP cleavage, and the number of TUNEL positive cells consistent with the induction of apoptosis. Propranolol and ICI 118551, but not atenolol, demonstrated a concentration-dependent inhibition of caspase 3-like activity. Propranolol and ICI 118551 directly inhibited the enzymatic activity of recombinant caspase 9 while atenolol did not; however, none of the β- adrenoceptor blockers that were examined directly blocked caspase 2 or 3 activity. In isolated mitochondria, propranolol and ICI 118551 inhibited staurosporine-induced cytochrome c release while atenolol did not. We conclude that propranolol and ICI 118551 protect SH-SY5Y cells against staurosporine-induced apoptosis through a dual action on the mitochondria and on caspase 9 in a cell type and an apoptotic paradigm where the conventional inhibitors of mitochondrial permeability transition such as cyclosporin A and bongkrekic acid demonstrate no protection. PMID:18534571

  17. Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells.

    PubMed

    Zhang, Nan; Wen, Qingping; Ren, Lu; Liang, Wenbo; Xia, Yang; Zhang, Xiaodan; Zhao, Dan; Sun, Dong; Hu, Yv; Hao, Haiguang; Yan, Yaping; Zhang, Guangxian; Yang, Jingxian; Kang, Tingguo

    2013-01-01

    Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB. PMID:24025424

  18. Tissue kallikrein induces SH-SY5Y cell proliferation via epidermal growth factor receptor and extracellular signal-regulated kinase1/2 pathway

    SciTech Connect

    Lu, Zhengyu; Yang, Qi; Cui, Mei; Liu, Yanping; Wang, Tao; Zhao, Hong; Dong, Qiang

    2014-03-28

    Highlights: • TK promotes EGFR phosphorylation in SH-SY5Y cells. • TK activates ERK1/2 and p38 phosphorylation in SH-SY5Y cells. • TK mediates SH-SY5Y cell proliferation via EGFR and ERK1/2 pathway. - Abstract: Tissue kallikrein (TK) is well known to take most of its biological functions through bradykinin receptors. In the present study, we found a novel signaling pathway mediated by TK through epidermal growth factor receptor (EGFR) in human SH-SY5Y cells. We discovered that TK facilitated the activation of EGFR, extracellular signal-regulated kinase (ERK) 1/2 and p38 cascade. Interestingly, not p38 but ERK1/2 phosphorylation was severely compromised in cells depleted of EGFR. Nevertheless, impairment of signaling of ERK1/2 seemed not to be restricted to EGFR phosphorylation. We also observed that TK stimulation could induce SH-SY5Y cell proliferation, which was reduced by EGFR down-regulation or ERK1/2 inhibitor. Overall, our findings provided convincing evidence that TK could mediate cell proliferation via EGFR and ERK1/2 pathway in vitro.

  19. Involvement of ERK1/2 pathway in neuroprotective effects of pyrroloquinoline quinine against rotenone-induced SH-SY5Y cell injury.

    PubMed

    Zhang, Q; Zhang, J; Jiang, C; Qin, J; Ke, K; Ding, F

    2014-06-13

    Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been shown to protect neurons against glutamate-induced damage both in vitro and in vivo. In this study, specific inhibitors to each of the mitochondrial complexes were used to find out which reactive oxygen species (ROS)-generating sites could be affected by PQQ. Then we established an in vitro model of Parkinson's disease (PD) by exposing cultured SH-SY5Y dopaminergic cells to rotenone, a complex I inhibitor. The neuroprotective effects of PQQ were observed by pretreatment of SH-SY5Y cells with PQQ before rotenone injury, and the possible involvement of certain signaling pathways were investigated. PQQ pretreatment prevented SH-SY5Y cells from rotenone-induced apoptosis in a concentration-dependent manner. PQQ neuroprotection was associated with inhibition of intracellular ROS production, modulation of the expression of apoptosis-related Bcl-2 and Bax, and regulation of the level of superoxide dismutase, glutathione, and malondialdehyde. Meanwhile, PQQ up-regulated the gene expression of Ndufs 1, 2, and 4 (complex I subunits), and increased mitochondrial viability and mitochondrial DNA content. Furthermore, PQQ pretreatment activated ERK1/2 phosphorylation in rotenone-injured SH-SY5Y cells, while ERK1/2 inhibition suppressed PQQ neuroprotection. All the results suggested that PQQ could protect SH-SY5Y cells against rotenone injury by reducing ROS production and maintaining mitochondrial functions through activation of ERK1/2 pathway. PMID:24755484

  20. Gene Expression Profile of NF-κB, Nrf2, Glycolytic, and p53 Pathways During the SH-SY5Y Neuronal Differentiation Mediated by Retinoic Acid.

    PubMed

    de Bittencourt Pasquali, Matheus Augusto; de Ramos, Vitor Miranda; Albanus, Ricardo D Oliveira; Kunzler, Alice; de Souza, Luis Henrinque Trentin; Dalmolin, Rodrigo Juliani Siqueira; Gelain, Daniel Pens; Ribeiro, Leila; Carro, Luigi; Moreira, José Cláudio Fonseca

    2016-01-01

    SH-SY5Y cells, a neuroblastoma cell line that is a well-established model system to study the initial phases of neuronal differentiation, have been used in studies to elucidate the mechanisms of neuronal differentiation. In the present study, we investigated alterations of gene expression in SH-SY5Y cells during neuronal differentiation mediated by retinoic acid (RA) treatment. We evaluated important pathways involving nuclear factor kappa B (NF-κB), nuclear E2-related factor 2 (Nrf2), glycolytic, and p53 during neuronal differentiation. We also investigated the involvement of reactive oxygen species (ROS) in modulating the gene expression profile of those pathways by antioxidant co-treatment with Trolox®, a hydrophilic analogue of α-tocopherol. We found that RA treatment increases levels of gene expression of NF-κB, glycolytic, and antioxidant pathway genes during neuronal differentiation of SH-SY5Y cells. We also found that ROS production induced by RA treatment in SH-SY5Y cells is involved in gene expression profile alterations, chiefly in NF-κB, and glycolytic pathways. Antioxidant co-treatment with Trolox® reversed the effects mediated by RA NF-κB, and glycolytic pathways gene expression. Interestingly, co-treatment with Trolox® did not reverse the effects in antioxidant gene expression mediated by RA in SH-SY5Y. To confirm neuronal differentiation, we quantified endogenous levels of tyrosine hydroxylase, a recognized marker of neuronal differentiation. Our data suggest that during neuronal differentiation mediated by RA, changes in profile gene expression of important pathways occur. These alterations are in part mediated by ROS production. Therefore, our results reinforce the importance in understanding the mechanism by which RA induces neuronal differentiation in SH-SY5Y cells, principally due this model being commonly used as a neuronal cell model in studies of neuronal pathologies. PMID:25465239

  1. Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells.

    PubMed

    Zaworski, P G; Alberts, G L; Pregenzer, J F; Im, W B; Slightom, J L; Gill, G S

    1999-11-01

    1 The D3 dopamine receptor presumably activates Gi/Go subtypes of G-proteins, like the structurally analogous D2 receptor, but its signalling targets have not been clearly established due to weak functional signals from cloned receptors as heterologously expressed in mostly non-neuronal cell lines. 2 In this study, recombinant human D3 receptors expressed in a human neuroblastoma cell line, SH-SY5Y, produced much greater signals than those expressed in a human embryonic kidney cell line, HEK293. Quinpirole, a prototypic agonist, markedly inhibited forskolin-stimulated cyclic AMP production and Ca2+-channel (N-type) currents in SH-SY5Y cells, and enhanced GTPgamma35S binding in isolated membranes, nearly ten times greater than that observed in HEK293 cell membranes. 3 GTPgamma35S-bound Galpha subunits from quinpirole-activated and solubilized membranes were monitored upon immobilization with various Galpha-specific antibodies. Galphao subunits (not Galphai) were highly labelled with GTPgamma35S in SH-SY5Y, but not in HEK293 cell membranes, despite their abundance in the both cell types, as shown with reverse transcription-polymerase chain reaction and Western blots. N-type Ca2+ channels and adenylyl cyclase V (D3-specific effector), on the other hand, exist only in SH-SY5Y cells. 4 More efficient coupling of the D3 receptor to Go subtypes in SH-SY5Y than HEK293 cells may be attributed, at least in part, to the two D3 neuronal effectors only present in SH-SY5Y cells (N-type Ca2+-channels and adenylyl cyclase V). The abundance of Go subtypes in the both cell lines seems to indicate their availability not a limiting factor. PMID:10578130

  2. Neuroprotective effect of 3,5-di-O-caffeoylquinic acid on SH-SY5Y cells and senescence-accelerated-prone mice 8 through the up-regulation of phosphoglycerate kinase-1.

    PubMed

    Han, J; Miyamae, Y; Shigemori, H; Isoda, H

    2010-09-01

    As aged population dramatically increases in these decades, efforts should be made on the intervention for curing age-associated neurologic degenerative diseases such as Alzheimer's disease (AD). Caffeoylquinic acid (CQA), an antioxidant component and its derivatives are natural functional compounds isolated from a variety of plants. In this study, we determined the neuroprotective effect of 3,5-di-O-CQA on Abeta(1-42) treated SH-SY5Y cells using MTT assay. To investigate the possible neuroprotective mechanism of 3,5-di-O-CQA, we performed proteomics analysis, real-time PCR analysis and measurement of the intracellular ATP level. In addition, we carried out the measurement of escape latency time to find the hidden platform in Morris water maze (MWM), real-time PCR using senescence-accelerated-prone mice (SAMP) 8 and senescence-accelerated-resistant mice (SAMR) 1 mice. Results showed that 3,5-di-O-CQA had neuroprotective effect on Abeta (1-42) treated cells. The mRNA expression of glycolytic enzyme (phosphoglycerate kinase-1; PGK1) and intracellular ATP level were increased in 3,5-di-O-CQA treated SH-SY5Y cells. We also found that 3,5-di-O-CQA administration induced the improvement of spatial learning and memory on SAMP8 mice, and the overexpression of PGK1 mRNA. These findings suggest that 3,5-di-O-CQA has a neuroprotective effect on neuron through the upregulation of PGK1 expression and ATP production activation. PMID:20570715

  3. Neurosupportive Role of Vanillin, a Natural Phenolic Compound, on Rotenone Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells

    PubMed Central

    Dhanalakshmi, Chinnasamy; Manivasagam, Thamilarasan; Nataraj, Jagatheesan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed

    2015-01-01

    Vanillin, a phenolic compound, has been reported to offer neuroprotection against experimental Huntington's disease and global ischemia by virtue of its antioxidant, anti-inflammatory, and antiapoptotic properties. The present study aims to elucidate the underlying neuroprotective mechanism of vanillin in rotenone induced neurotoxicity. Cell viability was assessed by exposing SH-SY5Y cells to various concentrations of rotenone (5–200 nM) for 24 h. The therapeutic effectiveness of vanillin against rotenone was measured by pretreatment of vanillin at various concentrations (5–200 nM) and then incubation with rotenone (100 nM). Using effective dose of vanillin (100 nM), mitochondrial membrane potential, levels of reactive oxygen species (ROS), and expression patterns of apoptotic markers were assessed. Toxicity of rotenone was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, release of cyt-c, and enhanced expressions of proapoptotic and downregulation of antiapoptotic indices via the upregulation of p38 and JNK-MAPK pathway proteins. Our results indicated that the pretreatment of vanillin attenuated rotenone induced mitochondrial dysfunction, oxidative stress, and apoptosis. Thus, vanillin may serve as a potent therapeutic agent in the future by virtue of its multiple pharmacological properties in the treatment of neurodegenerative diseases including PD. PMID:26664453

  4. Synthesis of amphiphilic resveratrol lipoconjugates and evaluation of their anticancer activity towards neuroblastoma SH-SY5Y cell line.

    PubMed

    Chillemi, Rosa; Cardullo, Nunzio; Greco, Valentina; Malfa, Giuseppe; Tomasello, Barbara; Sciuto, Sebastiano

    2015-01-01

    Resveratrol, a polyphenol present in grapes and other edible plants, possesses several important pharmacological activities, including anticancer activity. Nevertheless, its therapeutic use is still limited because of some unfavourable physicochemical and pharmacokinetic properties, mainly, poor cellular uptake and too rapid metabolism resulting in elimination from the body. To meet these drawbacks, some resveratrol conjugates would be useful, which would possess improved stability, uptake and bioavailability than the lead compound, and the ability to release it once it is internalized into the cell. In this paper we report a synthetic strategy which allowed us to obtain new amphiphilic resveratrol derivatives starting from different selectively protected resveratrol phosphoramidites or even from the resveratrol triphosphoramidite. Specifically, resveratrol was conjugated through phosphate bridge(s) to different lipophilic groups related to membrane lipids, such as cholesteryl or diacylglycero moieties. All the new lipoconjugates were tested towards human neuroblastoma SH-SY5Y cells and proved to be significantly more active than resveratrol, with a concentration-dependent activity. PMID:25932501

  5. Fipronil sulfone induced higher cytotoxicity than fipronil in SH-SY5Y cells: Protection by antioxidants.

    PubMed

    Romero, A; Ramos, E; Ares, I; Castellano, V; Martínez, M; Martínez-Larrañaga, M R; Anadón, A; Martínez, M A

    2016-06-11

    Fipronil is a broad spectrum insecticide from the phenyl pyrazole family, which targets GABA receptor. Limited information is available about the metabolite fipronil sulfone cytotoxic actions. This study examined in vitro neurotoxicity of fipronil and fipronil sulfone and evaluated Trolox (vitamin E analog) (0.3, 1μM), N-acetyl-cysteine (0.5, 1mM), melatonin (0.1, 1μM) and Tempol (superoxide dismutase analog) (0.3, 0.5mM) protective role in SH-SY5Y cells. MTT and LDH assays were carried out to assess the cytotoxicity of fipronil and fipronil sulfone at 3-100μM concentrations. Fipronil sulfone was more toxic than fipronil. Tempol showed the best neuroprotectant profile against fipronil (50 and 150μM) and fipronil sulfone (3 and 10μM) reaching control levels. Fipronil (100μM) and fipronil sulfone (3μM) treatments induced a 4.7- and 5-fold increases in lipid peroxides measured as malondialdehyde (MDA) and a 2.2- and 2.0-fold increases in the levels of nitric oxide (NO). These results suggest that oxidative stress observed may be one of the major mechanisms of fipronil-induced neurotoxicity and it may be attributed in part to fipronil disposition and metabolism. Our results led us postulate that metabolite fipronil sulfone might be responsible for the fipronil-induced toxicity rather than fipronil itself. PMID:27067106

  6. Toxic profile of bergamot essential oil on survival and proliferation of SH-SY5Y neuroblastoma cells.

    PubMed

    Berliocchi, Laura; Ciociaro, Antonella; Russo, Rossella; Cassiano, Maria Gilda Valentina; Blandini, Fabio; Rotiroti, Domenicantonio; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana

    2011-11-01

    Cosmetic, pharmaceutical, food and confectionary industries make increasing use of plant extracts in their products. Despite the widespread use of products containing plant extracts, the mechanisms of their effects are not fully characterized. Bergamot essential oil (BEO; Citrus bergamia, Risso) is a well-known plant extract used in aromatherapy and it has analgesic, anxiolytic and neuroprotective effects in rodents. To elicit neuroprotection, BEO recruits Akt prosurvival pathways. However, Akt stimulates cell proliferation, which may also pose risks for health in case of prolonged use. To study the potential effects of BEO on survival and proliferation of dividing cells, we selected human SH-SY5Y neuroblastoma cells. BEO triggered concentration-dependent mitochondrial dysfunction, cytoskeletal reorganization, cell shrinkage, DNA fragmentation and both caspase-dependent and independent cell death. Analysis of cleavage products of poly-(ADP-ribose) polymerase (PARP) revealed caspase-3 activation, but also activation of additional protease families. As result of increased proteolytic activity, Akt protein levels decreased in BEO-treated cells. Our data show that BEO can be lethal for dividing cells by activating multiple pathways. While this may reduce the risk of unwanted cell proliferation after prolonged use, it does suggest a cautionary approach to the use of inappropriate dilutions of the oil that may cause cell death. PMID:21878361

  7. Salvianolic Acid B Inhibits Aβ Generation by Modulating BACE1 Activity in SH-SY5Y-APPsw Cells.

    PubMed

    Tang, Ying; Huang, Dan; Zhang, Mei-Hua; Zhang, Wen-Sheng; Tang, Yu-Xin; Shi, Zheng-Xiang; Deng, Li; Zhou, Dai-Han; Lu, Xin-Yi

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease in humans. The accumulation of amyloid-β (Aβ) plays a critical role in the pathogenesis of AD. Previous studies indicated that Salvianolic acid B (SalB) could ameliorate Aβ-induced memory impairment. However, whether SalB could influence the generation of Aβ is unclear. Here, we show that SalB (25, 50, or 100 µM) reduces the generation of Aβ40 and Aβ42 in culture media by decreasing the protein expressions of BACE1 and sAPPβ in SH-SY5Y-APPsw cells. Meanwhile, SalB increases the levels of ADAM10 and sAPPα in the cells. However, SalB has no impact on the protein expressions of APP and PS1. Moreover, SalB attenuates oxidative stress and inhibits the activity of GSK3β, which might be related to the suppression of BACE1 expression and amyloidogenesis. Our study suggests that SalB is a promising therapeutic agent for AD by targeting Aβ generation. PMID:27258307

  8. Monocyte-mediated regulation of genes by the amyloid and prion peptides in SH-SY5Y neuroblastoma cells.

    PubMed

    Morte, Beatriz; Martínez, Tamara; Zambrano, Alberto; Pascual, Angel

    2011-05-01

    Alzheimer's disease as well as prion-related encephalopathies are neurodegenerative disorders of the central nervous system, which cause mental deterioration and progressive dementia. Both pathologies appear to be primarily associated with the pathological accumulation and deposit of β-amyloid or prion peptides in the brain, and it has been even suggested that neurotoxicity induced by these peptides would be associated to essentially similar pathogenic mechanisms, in particular to those that follow the activation of microglial cells. To probe whether the neurotoxic effects induced by the β-amyloid and prion peptides are actually mediated by similar glial-associated mechanisms, we have examined the differential expression of genes in SH-SY5Y neuroblastoma cells incubated with conditioned media from β-amyloid or prion-stimulated THP-1 monocytic cells. According to microarray analysis, not many coincidences are observed and only four genes (Hint3, Psph, Daam1 and c-Jun) appear to be commonly upregulated by both peptides. Furthermore, c-Jun appears to be involved in the cell death mediated by both peptides. PMID:21303680

  9. Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells.

    PubMed

    Faria, Juliana; Barbosa, Joana; Queirós, Odília; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2016-06-01

    Opioid therapy and abuse are increasing, justifying the need to study their toxicity and underlying mechanisms. Given opioid pharmacodynamics at the central nervous system, the analysis of toxic effects in neuronal models gains particular relevance. The aim of this study was to compare the toxicological effects of acute exposure to tramadol and tapentadol in the undifferentiated human SH-SY5Y neuroblastoma cell line. Upon exposure to tramadol and tapentadol concentrations up to 600μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death. Cell death was shown to predominantly occur through necrosis, with no alterations in membrane potential or in cytochrome c release. Both drugs were shown to stimulate glucose uptake and to cause ATP depletion, due to changes in the expression of energy metabolism enzymes. The toxicity mechanisms in such a neuronal model are relevant to understand adverse reactions to these opioids and to contribute to dose adjustment in order to avoid neurological damage. PMID:27317026

  10. Mitochondrial respiratory dysfunction due to the conversion of substituted cathinones to methylbenzamides in SH-SY5Y cells.

    PubMed

    den Hollander, Bjørnar; Sundström, Mira; Pelander, Anna; Siltanen, Antti; Ojanperä, Ilkka; Mervaala, Eero; Korpi, Esa R; Kankuri, Esko

    2015-01-01

    The increased use of cathinone-type designer drugs, known as legal highs, has led to concerns about their potential neurotoxicity due to their similarity to methamphetamine (METH). Therefore, closer investigations of their toxic effects are needed. We investigated the effects of the cathinones 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxymethcathinone (MDMC) and the amphetamine METH on cytotoxicity and mitochondrial respiration in SH-SY5Y neuroblastoma cells. We also investigated the contribution of reactive species, dopamine, Bcl-2 and tumor necrosis factor α (TNFα) on toxicity. Finally, we investigated the effect of cathinone breakdown products using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry and studied their involvement in toxicity. We observed dose-dependent increases in cytotoxicity and decreases in mitochondrial respiration following treatment with all cathinones and amphetamines. Glutathione depletion increases amphetamine, but not cathinone toxicity. Bcl-2 and TNFα pathways are involved in toxicity but dopamine levels are not. We also show that cathinones, but not amphetamines, spontaneously produce reactive species and cytotoxic methylbenzamide breakdown products when in aqueous solution. These results provide an important first insight into the mechanisms of cathinone cytotoxicity and pave the way for further studies on cathinone toxicity in vivo. PMID:26462443

  11. Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis

    SciTech Connect

    Wu, C.-W.; Ping, Y.-H.; Yen, J.-C.; Chang, C.-Y.; Wang, S.-F.; Yeh, C.-L.; Chi, C.-W.; Lee, H.-C. . E-mail: hclee2@ym.edu.tw

    2007-05-01

    Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in Brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects.

  12. Neuroprotective Effects of Geniposide in SH-SY5Y Cells and Primary Hippocampal Neurons Exposed to Aβ42

    PubMed Central

    Ding, Haimin; Liang, Mi; Li, Xiaojing; Mo, Weichuan; Wang, Xu; He, Rongqiao; Hua, Qian

    2014-01-01

    Our former studies have suggested that TongLuoJiuNao (TLJN) is clinically efficacious in the treatment of dementia and improving learning and memory in AD models. When Aβ aggregated with oligomer, it is known to be able to induce cellular toxicity as well as cognitive impairment. We tested the possibility that TLJN affects the formation of Aβ oligomers. In our experiment, TLJN improved cell viability, inhibited LDH release, and promoted the outgrowth of neurites of neurons treated with Aβ. Geniposide, the main component of TLJN, could increase the cell viability of SY5Y-APP695sw cells. The cytotoxicity of pretreated Aβ with geniposide was decreased in a dose-dependent manner. SDS-PAGE and Western blotting showed that geniposide and TLJN stimulated Aβ oligomer assembly. Compared with the control, more and longer fibrils of Aβ in the presence of geniposide were observed under electron microscope though the fibrils became less sensitive to thioflavin T staining. In sum, geniposide is able to protect neurons from Aβ-induced damage by remodeling Aβ. PMID:25506055

  13. TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

    SciTech Connect

    Pregi, Nicolas Wenker, Shirley; Vittori, Daniela; Leiros, Claudia Perez; Nesse, Alcira

    2009-02-01

    The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-{alpha}. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-{alpha} or pretreated with 25 U/ml Epo for 12 h before the addition of TNF-{alpha}. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-{kappa}B nuclear translocation, TNF-{alpha} induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-{kappa}B, through mechanisms involving Jak/STAT and PI3K signalling pathways.

  14. Salvianolic Acid B Inhibits Aβ Generation by Modulating BACE1 Activity in SH-SY5Y-APPsw Cells

    PubMed Central

    Tang, Ying; Huang, Dan; Zhang, Mei-Hua; Zhang, Wen-Sheng; Tang, Yu-Xin; Shi, Zheng-Xiang; Deng, Li; Zhou, Dai-Han; Lu, Xin-Yi

    2016-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disease in humans. The accumulation of amyloid-β (Aβ) plays a critical role in the pathogenesis of AD. Previous studies indicated that Salvianolic acid B (SalB) could ameliorate Aβ-induced memory impairment. However, whether SalB could influence the generation of Aβ is unclear. Here, we show that SalB (25, 50, or 100 µM) reduces the generation of Aβ40 and Aβ42 in culture media by decreasing the protein expressions of BACE1 and sAPPβ in SH-SY5Y-APPsw cells. Meanwhile, SalB increases the levels of ADAM10 and sAPPα in the cells. However, SalB has no impact on the protein expressions of APP and PS1. Moreover, SalB attenuates oxidative stress and inhibits the activity of GSK3β, which might be related to the suppression of BACE1 expression and amyloidogenesis. Our study suggests that SalB is a promising therapeutic agent for AD by targeting Aβ generation. PMID:27258307

  15. Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells.

    PubMed

    Tan, Jen-Kit; Then, Sue-Mian; Mazlan, Musalmah; Raja Abdul Rahman, Raja Noor Zaliha; Jamal, Rahman; Wan Ngah, Wan Zurinah

    2016-05-01

    Bcl-2 family proteins are crucial regulators of apoptosis. Both pro- and antiapoptotic members exist, and overexpression of the latter facilitates evasion of apoptosis in many cancer types. Bcl-2 homology domain 3 (BH3) mimetics are small molecule inhibitors of antiapoptotic Bcl-2 family members, and these inhibitors are promising anticancer agents. In this study, we report that gamma-tocotrienol (γT3), an isomer of vitamin E, can inhibit Bcl-2 to induce apoptosis. We demonstrate that γT3 induces cell death in human neuroblastoma SH-SY5Y cells by depolarising the mitochondrial membrane potential, enabling release of cytochrome c to the cytosol and increasing the activities of caspases-9 and -3. Treatment of cells with inhibitors of Bax or caspase-9 attenuated the cell death induced by γT3. Simulated docking analysis suggested that γT3 binds at the hydrophobic groove of Bcl-2, while a binding assay showed that γT3 competed with a fluorescent probe to bind at the hydrophobic groove. Our data suggest that γT3 mimics the action of BH3-only protein by binding to the hydrophobic groove of Bcl-2 and inducing apoptosis via the intrinsic pathway in a Bax- and caspase-9-dependent manner. PMID:27133421

  16. Nicorandil inhibits oxidative stress and amyloid-β precursor protein processing in SH-SY5Y cells overexpressing APPsw

    PubMed Central

    Kong, Jing-Jing; Zhang, Duo-Duo; Li, Pai; Wei, Chun-Yang; Yu, Hong-Jiu; Zhang, Hua; Zhang, Wei; Wang, Yan-Fu; Cao, Yun-Peng

    2015-01-01

    It has been demonstrated that ATP-sensitive potassium (KATP) channel activation has neuroprotective effects against neuronal damage induced by hypoxia, ischemia or metabolism stress. This study investigated the multiply protective effects of KATP channel opener nicorandil against neurotoxicity in SH-SY5Y cells transiently transfected with Swedish mutant APP (APPsw) and also the potential involvement of PI3K/Akt/GSK-3β pathway. Cells were treated with nicorandil (1 mM) for 24 h with and without glibenclamide (10 μM), a KATP channel inhibitor. Then the cells were collected for Hoechst33342, biochemical assays, real-time PCR, western blot and ELISA assay. Our results showed that nicorandil reduced apoptosis and decreased oxidative stress. Moreover, nicorandil down regulated APP695 mRNA and APP695 protein expression, also reduced Aβ1-42 levels in the medium. In addition, nicorandil increased the protein levels of p-Akt and p-GSK-3β by PI3K activation. Applying a PI3K inhibitor, LY294002 blocked the protection. These findings suggest nicorandil to be a potential therapeutic agent to treat Alzheimer’s disease (AD). PMID:25932125

  17. High Pressure synchrotron XRD and Raman studies of Ho0.5Y1.5Ti2O7

    NASA Astrophysics Data System (ADS)

    White, Melanie; Kumar, Ravhi; Baker, Jason; Light, Brian

    Pyrochlore oxides are of interest for their spin-frustrated systems and their proposed use in high-level nuclear waste management. We sought to examine the structural stability of these materials under extreme conditions in order to help determine their viability for applications. A compression and decompression study of Ho0.5Y1.5Ti2O7 was done in approximately 5 GPa intervals to above 55 GPa with both synchrotron powder x-ray diffraction at the Argonne National Laboratory Advanced Photon Source, and Raman spectroscopy at the University of Nevada - Las Vegas High Pressure Science and Engineering Center (HiPSEC). In both studies, pressurization of sample was achieved using a symmetric-style diamond anvil cell (DAC). The results are compared with the high pressure behavior of other rare earth titanates. A reversible phase transition is observed between 45 and 49 GPa in both studies. The x-ray diffraction patterns are analyzed in order to identify the crystal structure of the new phase. Vibrational modes are assigned to the Raman spectra and tracked as a function of pressure. Our poster will discuss the results in detail. This research was sponsored by the NNSA under the SSAA program through the DOE Cooperative Agreement #DE-NA0001982. Portions of this study were performed at HPCAT (Sector 16) Advanced Photon Source (APS), Argonne National Laboratory.

  18. Mitochondrial respiratory dysfunction due to the conversion of substituted cathinones to methylbenzamides in SH-SY5Y cells

    PubMed Central

    den Hollander, Bjørnar; Sundström, Mira; Pelander, Anna; Siltanen, Antti; Ojanperä, Ilkka; Mervaala, Eero; Korpi, Esa R.; Kankuri, Esko

    2015-01-01

    The increased use of cathinone-type designer drugs, known as legal highs, has led to concerns about their potential neurotoxicity due to their similarity to methamphetamine (METH). Therefore, closer investigations of their toxic effects are needed. We investigated the effects of the cathinones 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxymethcathinone (MDMC) and the amphetamine METH on cytotoxicity and mitochondrial respiration in SH-SY5Y neuroblastoma cells. We also investigated the contribution of reactive species, dopamine, Bcl-2 and tumor necrosis factor α (TNFα) on toxicity. Finally, we investigated the effect of cathinone breakdown products using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry and studied their involvement in toxicity. We observed dose-dependent increases in cytotoxicity and decreases in mitochondrial respiration following treatment with all cathinones and amphetamines. Glutathione depletion increases amphetamine, but not cathinone toxicity. Bcl-2 and TNFα pathways are involved in toxicity but dopamine levels are not. We also show that cathinones, but not amphetamines, spontaneously produce reactive species and cytotoxic methylbenzamide breakdown products when in aqueous solution. These results provide an important first insight into the mechanisms of cathinone cytotoxicity and pave the way for further studies on cathinone toxicity in vivo. PMID:26462443

  19. Antihypoxic effect of miR-24 in SH-SY5Y cells under hypoxia via downregulating expression of neurocan.

    PubMed

    Sun, Xingyuan; Ren, Zhanjun; Pan, Yunzhi; Zhang, Chenxin

    2016-09-01

    Hypoxia-induced apoptosis-related mechanisms involved in the brain damage following cerebral ischemia injury. A subset of the small noncoding microRNA (miRNAs) is regulated by tissue oxygen levels, and miR-24 was found to be activated by hypoxic conditions. However, the roles of miR-24 and its target gene in neuron are not well understood. Here, we validated miRNA-24 is down-regulated in patients with cerebral infarction. Hypoxia suppressed the expression of miR-24, but increased the expression of neurocan in both mRNA and protein levels in SH-SY5Y cells. MiR-24 mimics reduced the expression of neurocan, suppressed cell apoptosis, induced cell cycle progression and cell proliferation in SH-SY5Y cells under hypoxia. By luciferase reporter assay, neurocan is validated a direct target gene of miR-24. Furthermore, knockdown of neurocan suppressed cell apoptosis, induced cell cycle progression and cell proliferation in SH-SY5Y cells under hypoxia. Taken together, miR-24 overexpression or silencing of neurocan shows an antihypoxic effect in SH-SY5Y cells. Therefore, miR-24 and neurocan play critical roles in neuron cell apoptosis and are potential therapeutic targets for ischemic brain disease. PMID:27349868

  20. PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells.

    PubMed

    Zhang, Hong-Tao; Mi, Lan; Wang, Ting; Yuan, Lan; Li, Xue-Hui; Dong, Li-Sha; Zhao, Peng; Fu, Juan-Ling; Yao, Bi-Yun; Zhou, Zong-Can

    2016-08-01

    Manganese (Mn) as an environmental risk factor of Parkinson's disease (PD) is considered to cause manganism. Mitophagy is thought to play a key role in elimination the injured mitochondria. The goal of this paper was to explore whether the PINK1/Parkin-mediated mitophagy is activated and its role in Mn-induced mitochondrial dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/ΔΨm) and apoptosis by FACS and examined PINK1/Parkin-mediated mitophagy by western-blotting and the co-localization of mitochondria and acidic lysosomes. Further, we explore the role of mitophagy in Mn-induced apoptosis by inhibition the mitophagy by knockdown Parkin level. Results show that MnCl2 dose-dependently caused ΔΨm decrease, ROS generation and apoptosis of dopaminergic SH-SY5Y cells. Moreover, Mn could induce mitophagy and PINK1/Parkin-mediated pathway was activated in SH-SY5Y cells. Transient transfection of Parkin siRNA knockdown the expressing level of parkin inhibited Mn-induced mitophagy and aggravated apoptosis of SH-SY5Y cells. In conclusion, our study demonstrated that Mn may induce PINK1/Parkin-mediated mitophagy, which may exert significant neuro-protective effect against Mn-induced dopaminergic neuronal cells apoptosis. PMID:27091500

  1. SOD3 Ameliorates H2O2-Induced Oxidative Damage in SH-SY5Y Cells by Inhibiting the Mitochondrial Pathway.

    PubMed

    Yang, Rong; Wei, Li; Fu, Qing-Qing; Wang, Hua; You, Hua; Yu, Hua-Rong

    2016-07-01

    This study was designed to investigate the protective effects of extracellular superoxide dismutase (SOD3) against hydrogen peroxide (H2O2) induced damage in human neuroblastoma SH-SY5Y cells and to elucidate the mechanisms responsible for this beneficial effect. SOD3-overexpressing SH-SY5Y cells were generated by adenoviral vector-mediated infection, and H2O2 was then added into the cell culture system to establish an in vitro model of oxidative stress. Cell viability, the generation of intracellular reactive oxygen species (ROS), the expression and activity of antioxidant enzymes, the levels of lipid peroxidation malondialdehyde (MDA), the expression of mitochondrial apoptosis-related genes, and calcium imaging were examined. Following H2O2 exposure, the over-expression of SOD3 promoted the survival of SH-SY5Y cells; decreased the production of ROS, MDA levels, cytochrome C, caspase-3, caspase-9, and Bax gene expression, and calcium levels; and increased the expression and activity of antioxidant enzyme genes and the expression level of Bcl-2. Together, our data demonstrate that SOD3 ameliorates H2O2-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial pathway and provide new insights into the functional actions of SOD3 on oxidative stress-induced cell damage. PMID:27084770

  2. Vitamin E, γ-tocotrienol, Protects Against Buthionine Sulfoximine-Induced Cell Death by Scavenging Free Radicals in SH-SY5Y Neuroblastoma Cells.

    PubMed

    Tan, Jen-Kit; Then, Sue-Mian; Mazlan, Musalmah; Jamal, Rahman; Ngah, Wan Zurinah Wan

    2016-04-01

    The induction of reactive oxygen species (ROS) to selectively kill cancer cells is an important feature of radiotherapy and various chemotherapies. Depletion of glutathione can induce apoptosis in cancer cells or sensitize them to anticancer treatments intended to modulate ROS levels. In contrast, antioxidants protect cancer cells from oxidative stress-induced cell death by scavenging ROS. The role of exogenous antioxidants in cancer cells under oxidative insults remains controversial and unclear. This study aimed to identify protective pathways modulated by γ-tocotrienol (γT3), an isomer of vitamin E, in human neuroblastoma SH-SY5Y cells under oxidative stress. Using buthionine sulfoximine (BSO) as an inhibitor of glutathione synthesis, we found that BSO treatment reduced the viability of SH-SY5Y cells. BSO induced cell death by increasing apoptosis, decreased the level of reduced glutathione (GSH), and increased ROS levels in SH-SY5Y cells. Addition of γT3 increased the viability of BSO-treated cells, suppressed apoptosis, and decreased the ROS level induced by BSO, while the GSH level was unaffected. These results suggest that decreasing GSH levels by BSO increased ROS levels, leading to apoptosis in SH-SY5Y cells. γT3 attenuated the BSO-induced cell death by scavenging free radicals. PMID:27008382

  3. Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways.

    PubMed

    Dayem, Ahmed Abdal; Kim, BongWoo; Gurunathan, Sangiliyandi; Choi, Hye Yeon; Yang, Gwangmo; Saha, Subbroto Kumar; Han, Dawoon; Han, Jihae; Kim, Kyeongseok; Kim, Jin-Hoi; Cho, Ssang-Goo

    2014-07-01

    Nano-scale materials are noted for unique properties, distinct from those of their bulk material equivalents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Human neuroblastoma SH-SY5Y cells are considered an ideal in vitro model for studying neurogenesis, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and downregulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs modulate the intracellular signaling pathways, leading to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy. PMID:24827677

  4. Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathwayss.

    PubMed

    Dayem, Ahmed Abdal; Kim, Bongwoo; Gurunathan, Sangiliyandi; Choi, Hye Yeon; Yang, Gwangmo; Saha, Subbroto Kumar; Han, Dawoon; Han, Jihae; Kim, Kyeongseok; Kim, Jin-Hoi; Cho, Ssang-Goo

    2014-04-22

    The relevant in vitro cellular model resembling functional neurons is important for the mechanistic research on various neuronal diseases. Human neuroblastoma SH-SY5Y cells may be considered one of the ideal in vitro models for studying neuroscience, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and down-regulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs could modulate the intracellular signaling pathways to lead to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy. PMID:24753441

  5. Neuroprotective Effects of Methyl 3,4-Dihydroxybenzoate against TBHP-Induced Oxidative Damage in SH-SY5Y Cells.

    PubMed

    Cai, Liang; Wang, Li-Fang; Pan, Jun-Ping; Mi, Xiang-Nan; Zhang, Zheng; Geng, Hai-Ju; Wang, Jia-Hui; Hu, Song-Hui; Zhang, Wei; Gao, Qin; Wu, Wu-Tian; Luo, Huan-Min

    2016-01-01

    This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB or N-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 μM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells. PMID:27556437

  6. Luminescence and magnetic properties of novel nanoparticle-sheathed 3D Micro-Architectures of Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) for bifunctional application

    NASA Astrophysics Data System (ADS)

    Krishnan, Rajagopalan; Thirumalai, Jagannathan; Kathiravan, Arunkumar

    2015-01-01

    For the first time, we report the successful synthesis of novel nanoparticle-sheathed bipyramid-like and almond-like Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) 3D hierarchical microstructures through a simple disodium ethylenediaminetetraacetic acid (Na2EDTA) facilitated hydrothermal method. Interestingly, time-dependent experiments confirm that the assembly-disassembly process is responsible for the formation of self-aggregated 3D architectures via Ostwald ripening phenomena. The resultant products are characterized by x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), photoluminescence (PL), and magnetic measurements. The growth and formation mechanisms of the self-assembled 3D micro structures are discussed in detail. To confirm the presence of all the elements in the microstructure, the energy loss induced by the K, L shell electron ionization is observed in order to map the Fe, Gd, Mo, O, and Eu components. The photo luminescence properties of Fe0.5R0.5(MoO4)1.5 doped with Eu3+, Tb3+, Dy3+ are investigated. The room temperature and low temperature magnetic properties suggest that the interaction between the local-fields introduced by the magnetic Fe3+ ions and the R3+ (La, Gd) ions in the dodecahedral sites determine the magnetism in Fe0.5R0.5(MoO4)1.5:Eu3+. This work provides a new approach to synthesizing the novel Fe0.5R0.5(MoO4)1.5:Ln3+ for bi-functional magnetic and luminescence applications.

  7. Estrogen-related receptor gamma regulates dopaminergic neuronal phenotype by activating GSK3β/NFAT signaling in SH-SY5Y cells.

    PubMed

    Lim, Juhee; Choi, Hueng-Sik; Choi, Hyun Jin

    2015-05-01

    The orphan nuclear receptor estrogen-related receptor gamma (ERRγ) is highly expressed in the nervous system during embryogenesis and in adult brains, but its physiological role in neuronal development remains unknown. In this study, we evaluated the relevance of ERRγ in regulating dopaminergic (DAergic) phenotype and the corresponding signaling pathway. We used retinoic acid (RA) to differentiate human neuroblastoma SH-SY5Y cells. RA induced neurite outgrowth of SH-SY5Y cells with an increase in DAergic neuron-like properties, including up-regulation of tyrosine hydroxylase, dopamine transporter, and vesicular monoamine transporter 2. ERRγ, but not ERRα, was up-regulated by RA, and participated in RA effect on SH-SY5Y cells. ERRγ over-expression enhanced mature DAergic neuronal phenotype with neurite outgrowth as with RA treatment; and RA-induced increase in DAergic phenotype was attenuated by silencing ERRγ expression. ERRγ appears to have a crucial role in morphological and functional regulation of cells that is selective for DAergic neurons. Polo-like kinase 2 was up-regulated in ERRγ-over-expressing SH-SY5Y cells, which was involved in phosphorylation of glycogen synthase kinase 3β and resulting downstream activation of nuclear factor of activated T cells. The likely involvement of ERRγ in regulating the DAergic neuronal phenotype makes this orphan nuclear receptor a novel target for understanding DAergic neuronal differentiation. We propose the relevance of estrogen-related receptor gamma (ERRγ) in regulating dopaminergic neuronal phenotype: ERRγ is up-regulated by retinoic acid in SH-SY5Y cells, and enhances dopaminergic phenotypes and induces neurite outgrowth; Polo-like kinase 2 (PLK2) and glycogen synthase kinase 3 beta/nuclear factor of activated T cells (GSK3β/NFAT) signaling are responsible for the ERRγ effect. Our findings provide the first insights into the role of ERRγ in the brain, as a novel approach toward understanding

  8. Assessment of cellular responses after short- and long-term exposure to silver nanoparticles in human neuroblastoma (SH-SY5Y) and astrocytoma (D384) cells.

    PubMed

    Coccini, Teresa; Manzo, Luigi; Bellotti, Vittorio; De Simone, Uliana

    2014-01-01

    Silver nanoparticle (AgNP, 20 nm) neurotoxicity was evaluated by an integrated in vitro testing protocol employing human cerebral (SH-SY5Y and D384) cell lines. Cellular response after short-term (4-48 h, 1-100 μ g/ml) and prolonged exposure (up to 10 days, 0.5-50 μ g/ml) to AgNP was assessed by MTT, calcein-AM/PI, clonogenic tests. Pulmonary A549 cells were employed for data comparison along with silver nitrate as metal ionic form. Short-term data: (i) AgNP produced dose- and time-dependent mitochondrial metabolism changes and cell membrane damage (effects starting at 25 μ g/ml after 4 h: EC50s were 40.7 ± 2.0 and 49.5 ± 2.1 μ g/ml for SH-SY5Y and D384, respectively). A549 were less vulnerable; (ii) AgNP doses of ≤ 18 μ g/ml were noncytotoxic; (iii) AgNO3 induced more pronounced effects compared to AgNP on cerebral cells. Long-term data: (i) low AgNP doses (≤ 1 μ g/ml) compromised proliferative capacity of all cell types (cell sensibility: SHSY5Y > A549 > D384). Colony number decrease in SH-SY5Y and D384 was 50% and 25%, respectively, at 1 μ g/ml, and lower dose (0.5 μ g/ml) was significantly effective towards SH-SY5Y and pulmonary cells; (ii) cell proliferation activity was more affected by AgNO3 than AgNPs. In summary, AgNP-induced cytotoxic effects after short-term and prolonged exposure (even at low doses) were evidenced regardless of cell model types. PMID:24693232

  9. Assessment of Cellular Responses after Short- and Long-Term Exposure to Silver Nanoparticles in Human Neuroblastoma (SH-SY5Y) and Astrocytoma (D384) Cells

    PubMed Central

    Manzo, Luigi; Bellotti, Vittorio

    2014-01-01

    Silver nanoparticle (AgNP, 20 nm) neurotoxicity was evaluated by an integrated in vitro testing protocol employing human cerebral (SH-SY5Y and D384) cell lines. Cellular response after short-term (4–48 h, 1–100 μg/ml) and prolonged exposure (up to 10 days, 0.5–50 μg/ml) to AgNP was assessed by MTT, calcein-AM/PI, clonogenic tests. Pulmonary A549 cells were employed for data comparison along with silver nitrate as metal ionic form. Short-term data: (i) AgNP produced dose- and time-dependent mitochondrial metabolism changes and cell membrane damage (effects starting at 25 μg/ml after 4 h: EC50s were 40.7 ± 2.0 and 49.5 ± 2.1 μg/ml for SH-SY5Y and D384, respectively). A549 were less vulnerable; (ii) AgNP doses of ≤ 18 μg/ml were noncytotoxic; (iii) AgNO3 induced more pronounced effects compared to AgNP on cerebral cells. Long-term data: (i) low AgNP doses (≤1 μg/ml) compromised proliferative capacity of all cell types (cell sensibility: SHSY5Y > A549 > D384). Colony number decrease in SH-SY5Y and D384 was 50% and 25%, respectively, at 1 μg/ml, and lower dose (0.5 μg/ml) was significantly effective towards SH-SY5Y and pulmonary cells; (ii) cell proliferation activity was more affected by AgNO3 than AgNPs. In summary, AgNP-induced cytotoxic effects after short-term and prolonged exposure (even at low doses) were evidenced regardless of cell model types. PMID:24693232

  10. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2)-M17 Neuroblastoma Cell Lines upon Differentiation

    PubMed Central

    Filograna, Roberta; Civiero, Laura; Ferrari, Vanni; Codolo, Gaia; Greggio, Elisa; Bubacco, Luigi; Beltramini, Mariano; Bisaglia, Marco

    2015-01-01

    Human cell lines are often used to investigate cellular pathways relevant for physiological or pathological processes or to evaluate cell toxicity or protection induced by different compounds, including potential drugs. In this study, we analyzed and compared the differentiating activities of three agents (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate) on the human neuroblastoma SH-SY5Y and BE(2)-M17 cell lines; the first cell line is largely used in the field of neuroscience, while the second is still poorly characterized. After evaluating their effects in terms of cell proliferation and morphology, we investigated their catecholaminergic properties by assessing the expression profiles of the major genes involved in catecholamine synthesis and storage and the cellular concentrations of the neurotransmitters dopamine and noradrenaline. Our results demonstrate that the two cell lines possess similar abilities to differentiate and acquire a neuron-like morphology. The most evident effects in SH-SY5Y cells were observed in the presence of staurosporine, while in BE(2)-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH-SY5Y and BE(2)-M17 cells are characterized by the production of both NA and DA, but their levels are considerably higher in BE(2)-M17 cells. Moreover, the NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2)-M17 cells have a more prominent DAergic phenotype. Finally, the catecholamine concentration strongly increases upon differentiation induced by staurosporine in both cell lines. In conclusion, in this work the catecholaminergic phenotype of the human BE(2)-M17 cell line upon differentiation was characterized for the first time. Our data suggest that SH-SY5Y and BE(2)-M17 represent two alternative cell models for the neuroscience field. PMID:26317353

  11. Neurofunctional endpoints assessed in human neuroblastoma SH-SY5Y cells for estimation of acute systemic toxicity

    SciTech Connect

    Gustafsson, Helena; Runesson, Johan; Lundqvist, Jessica; Lindegren, Helene; Axelsson, Viktoria; Forsby, Anna

    2010-06-01

    The objective of the EU-funded integrated project ACuteTox is to develop a strategy in which general cytotoxicity, together with organ-specific toxicity and biokinetic features, are used for the estimation of human acute systemic toxicity. Our role in the project is to characterise the effect of reference chemicals with regard to neurotoxicity. We studied cell membrane potential (CMP), noradrenalin (NA) uptake, acetylcholine esterase (AChE) activity, acetylcholine receptor (AChR) signalling and voltage-operated calcium channel (VOCC) function in human neuroblastoma SH-SY5Y cells after exposure to 23 pharmaceuticals, pesticides or industrial chemicals. Neurotoxic alert chemicals were identified by comparing the obtained data with cytotoxicity data from the neutral red uptake assay in 3T3 mouse fibroblasts. Furthermore, neurotoxic concentrations were correlated with estimated human lethal blood concentrations (LC50). The CMP assay was the most sensitive assay, identifying eight chemicals as neurotoxic alerts and improving the LC50 correlation for nicotine, lindane, atropine and methadone. The NA uptake assay identified five neurotoxic alert chemicals and improved the LC50 correlation for atropine, diazepam, verapamil and methadone. The AChE, AChR and VOCC assays showed limited potential for detection of acute toxicity. The CMP assay was further evaluated by testing 36 additional reference chemicals. Five neurotoxic alert chemicals were generated and orphendrine and amitriptyline showed improved LC50 correlation. Due to the high sensitivity and the simplicity of the test protocol, the CMP assay constitutes a good candidate assay to be included in an in vitro test strategy for prediction of acute systemic toxicity.

  12. Antioxidant and Proliferative Activities of Bupleuri Radix Extract Against Serum Deprivation in SH-SY5Y Cells

    PubMed Central

    Seo, Mi Kyoung; Cho, Hye Yeon; Lee, Chan Hong; Koo, Kyung Ah; Park, Yong Ki; Lee, Jung Goo; Lee, Bong Ju

    2013-01-01

    Objective Bupleuri Radix (BR) is a major component of several Oriental herbal medicines used to treat stress and mental illness. There are evidences that antidepressant drugs modulate oxidative damage implicated in the pathophysiology of neuropsychiatric disorder, including depression. The aim of the present study was to investigate antioxidant and proliferative effects of BR against oxidative stress induced by serum deprivation in SH-SY5Y cells. Methods We examined the antioxidant effects of BR on a number of measures, including cell viability, formation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and levels of both Bcl-2 and Bax. We also investigated the effects of BR on cell proliferation using the bromodeoxyuridine (BrdU) assay, and used Western blot analysis to measure changes in expression of the cell cycle phase regulators. Results 1) Serum deprivation significantly induced the loss of cell viability, the formation of ROS, the reduction of SOD activity, down-regulation of Bcl-2 expression and up-regulation of Bax expression. However, BR extract reversed these effects in dose-dependent manner. 2) Serum deprivation significantly reduced cell proliferation. Western blot analysis revealed that serum deprivation significantly decreased cyclinD1 and phosphorylated retinoblastoma (pRb) expression, and increased p27 expression. On the other hand, BR dose dependently reversed these effects. Conclusion This study suggests that aqueous extract of BR may exert potent antioxidant effects and also play an important role in regulating cell cycle progression during neurogenesis. These effects of BR may be a potentially important mechanism of antidepressant underlying the observed antioxidant and proliferative effects. PMID:23483021

  13. Effect of toluene diisocyanate on homeostasis of intracellular-free calcium in human neuroblastoma SH-SY5Y Cells

    SciTech Connect

    Liu, P.-S. . E-mail: psliu@mail.scu.edu.tw; Chiung, Y.-M.; Kao, Y.-Y.

    2006-03-01

    The mechanisms of TDI (2,4-toluene diisocyanate)-induced occupational asthma are not fully established. Previous studies have indicated that TDI induces non-specific bronchial hyperreactivity to methacholine and induces contraction of smooth muscle tissue by activating 'capsaicin-sensitive' nerves resulting asthma. Cytosolic-free calcium ion concentrations ([Ca{sup 2+}]{sub c}) are elevated when either capsaicin acts at vanilloid receptors, or methacholine at muscarinic receptors. This study therefore investigated the effects of TDI on Ca{sup 2+} mobilization in human neuroblastoma SH-SY5Y cells. TDI was found to elevate [Ca{sup 2+}]{sub c} by releasing Ca{sup 2+} from the intracellular stores and extracellular Ca{sup 2+} influx. 500 {mu}M TDI induced a net [Ca{sup 2+}]{sub c} increase of 112 {+-} 8 and 78 {+-} 6 nM in the presence and absence of extracellular Ca{sup 2+}, respectively. In Ca{sup 2+}-free buffer, TDI induced Ca{sup 2+} release from internal stores to reduce their Ca{sup 2+} content and this reduction was evidenced by a suppression occurring on the [Ca{sup 2+}]{sub c} rise induced by thapsigargin, ionomycin, and methacholine after TDI incubation. In the presence of extracellular Ca{sup 2+}, simultaneous exposure to TDI and methacholine led a higher level of [Ca{sup 2+}]{sub c} compared to single methacholine stimulation, that might explain that TDI induces bronchial hyperreactivity to methacholine. We conclude that TDI is capable of interfering the [Ca{sup 2+}]{sub c} homeostasis including releasing Ca{sup 2+} from internal stores and inducing extracellular Ca{sup 2+} influx. The interaction of this novel character and bronchial hyperreactivity need further investigation.

  14. Effects of ethylene glycol ethers on cell viability in the human neuroblastoma SH-SY5Y cell line.

    PubMed

    Regulska, Magdalena; Pomierny, Bartosz; Basta-Kaim, Agnieszka; Starek, Andrzej; Filip, Małgorzata; Lasoń, Władysław; Budziszewska, Bogusława

    2010-01-01

    Ethylene glycol ethers (EGEs) are a class of chemicals used extensively in the manufacture of a wide range of domestic and industrial products, which may result in human exposure and toxicity. Hematologic and reproductive toxicity of EGEs are well known whereas their action on neuronal cell viability has not been studied so far. In the present study, we investigated the effects of some EGEs on cell viability and on the hydrogen peroxide-induced damage in the human neuroblastoma (SH-SY5Y) cells. It has been found that 2-phenoxyethanol in a concentration-dependent manner (5-25 mM, 24 h) increased the basal and H(2)O(2)-induced lactate dehydrogenase (LDH) release and 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyl tetrazolium bromide (MTT) reduction. 2-Butoxyethanol given alone did not affect LDH release and MTT reduction but concentration-dependently enhanced the cytotoxic effect of H(2)O(2). 2-Isopropoxyethanol significantly and concentration-dependently (1-25 mM) increased the basal LDH release and attenuated MTT reduction, but did not potentiate the cytotoxic effect of H(2)O(2). Contrary to this, 2-methoxyethanol did not show a cytotoxic effect while 2-ethoxyethanol at high concentrations intensified the hydrogen peroxide action. This study demonstrated that among the EGEs studied, 2-phenoxyethanol showed the most consistent cytotoxic effect on neurons in in vitro conditions and enhanced the hydrogen peroxide action. 2-Isopropoxyethanol had also a potent cytotoxic effect, but it did not enhance the hydrogen peroxide action, whereas 2-butoxyethanol only potentiated cytotoxic effect of H(2)O(2). It is concluded that the results of the present study should be confirmed in in vivo conditions and that some EGEs, especially 2-phenoxyethanol, 2-butoxyethanol and 2-isopropoxyethanol, may be responsible for initiation or exacerbation of neuronal cell damage. PMID:21273685

  15. Force spectroscopy of membrane hardness of SH-SY5Y neuroblastoma cells before and after differentiation

    NASA Astrophysics Data System (ADS)

    Kwon, Sangwoo; Yang, Woochul; Choi, Yun Kyong; Park, Jung Keuck

    2014-05-01

    Atomic force microscopy (AFM) is utilized in many studies for measuring the structure and the physical characteristics of soft and bio materials. In particular, the force spectroscopy function in the AFM system allows us to explore the mechanical properties of bio cells. In this study, we probe the variation in the membrane hardness of human neuroblastoma SH-SY5Y cells (SH-cells) before and after differentiation by using force spectroscopy. The SH-cell, which is usually differentiated by using a chemical treatment with retinoic acid (RA), is a neuronal cell line employed widely as an in-vitro model for neuroscience research. In force spectroscopy, the force-distance curves are obtained from both the original and the RA-treated cells while the AFM tip approaches and pushes on the cell membranes. The slope deduced from linear region in the force-distance curve is the spring constant and corresponds to the hardness of the cell membrane. The spring constant of the RA-treated cells (0.597 ± 0.010 nN/nm) was smaller than that of the original cells (0.794 ± 0.010 nN/nm), reflecting a hardness decrease in the cells differentiated with the RA treatments. The results clearly demonstrated that the differentiated cells are softer than the original cells. The change in the elasticity of the differentiated cells might be caused by morphological modification during differentiation process. We suggest that force spectroscopy can be employed as a novel method to determine the degree of differentiation of stem cells into various functional cells.

  16. Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by l-carnosine in SH-SY5Y cells.

    PubMed

    Oh, Yun-Mi; Jang, Eun-Hee; Ko, Jeong-Hyeon; Kang, Ju-Hee; Park, Chang-Shin; Han, Seung Baik; Kim, Jun Sig; Kim, Kyung Hwan; Pie, Jae-Eun; Shin, Dong Wun

    2009-07-31

    Conditions that cause endoplasmic reticulum malfunction (ER stress) play a key role in the development of various human diseases including neurodegenerative diseases. Carnosine is an endogenous peptide, present in excitable tissues such as brain and skeletal muscle. Although there are reports suggesting that carnosine has a biological role independent of its antioxidant activity, there have been no reports of the effects of carnosine on the ER stress response. We investigated the effects of carnosine on 6-hydroxydopamine (6-OHDA)-induced cell death and ER stress in SH-SY5Y cells. After assessing control cell viability in serum-free conditions for 24h (100% viability), we found that 50 microM 6-OHDA reduced cell viability to 76.4% of control values, whereas addition of 10mM carnosine significantly reduced cell death to 96.1% viability in a dose-dependent manner. Consistent with its cytoprotective action, carnosine markedly inhibited subsequent ER stress responses, including phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) and c-jun, expression of glucose regulatory protein 78 and C/EBP homologous protein, and mRNA splicing of X-box protein 1. The measurement of reactive oxygen species (ROS) generation by 6-OHDA showed that addition of 10mM carnosine slightly but obviously inhibits the 6-OHDA-induced ROS production. In conclusion, our results show that carnosine almost completely inhibits 6-OHDA-induced ER stress responses and cytotoxicity, and that slight antioxidant activity of carnosine against 6-OHDA is observed. Further in vivo studies are needed to investigate clinical uses for carnosine. PMID:19394406

  17. The effect of UV-filters on the viability of neuroblastoma (SH-SY5Y) cell line.

    PubMed

    Broniowska, Żaneta; Pomierny, Bartosz; Smaga, Irena; Filip, Małgorzata; Budziszewska, Bogusława

    2016-05-01

    Topical application of cosmetic products, containing ultraviolet filters (UV filters) are recommended as a protection against sunburns and in order to reduce the risk of skin cancer. However, some UV filters can be absorbed through skin and by consuming contaminated food. Among the chemical UV filters, benzophenone-3 (BP-3), 3-(4-methylbenzylidene)camphor (4-MBC) and 2-ethylhexyl-4-methoxycinnamate (OMC) are absorbed through the skin to the greatest extent. So far, these lipophilic compounds were demonstrated to influence the gonadal and thyroid hormone function, but their effect on central nervous system cells has not been investigated, yet. In the present study, we investigated the effect of some UV filters on cell viability and caspase-3 activity in SH-SY5Y cells. It has been found that benzophenone-2 (BP-2), BP-3, 4-methylbenzophenone (4-MBP) and OMC present in the culture medium for 72h in high concentration (10(-5) and 10(-4)M) and 4-MBC only 10(-4)M produced a significant cytotoxic effect, as determined both by the MTT reduction test and LDH release assay. In contrast to necrotic changes, all tested UV filters increased caspase-3 activity in much lower concentrations (from 10(-8) to 10(-7)M). Proapoptotic properties of the test compounds were positively verified by Hoechst staining. The obtained results indicated that UV filters adversely affected the viability of nerve cells, most likely by enhancing the process of apoptosis. The most potent effect was exerted by BP-3 and 4-MBC and at concentrations that may be reached in vivo. Since human exposure to UV filters is significant these compound should be taken into consideration as one of the possible factors involved in pathogenesis of neurodegenerative diseases. PMID:26965011

  18. Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization

    PubMed Central

    2012-01-01

    Background Okadaic acid (OA), a toxin produced by several dinoflagellate species is responsible for frequent food poisonings associated to shellfish consumption. Although several studies have documented the OA effects on different processes such as cell transformation, apoptosis, DNA repair or embryogenesis, the molecular mechanistic basis for these and other effects is not completely understood and the number of controversial data on OA is increasing in the literature. Results In this study, we used suppression subtractive hybridization in SHSY5Y cells to identify genes that are differentially expressed after OA exposure for different times (3, 24 and 48 h). A total of 247 subtracted clones which shared high homology with known genes were isolated. Among these, 5 specific genes associated with cytoskeleton and neurotransmission processes (NEFM, TUBB, SEPT7, SYT4 and NPY) were selected to confirm their expression levels by real-time PCR. Significant down-regulation of these genes was obtained at the short term (3 and 24 h OA exposure), excepting for NEFM, but their expression was similar to the controls at 48 h. Conclusions From all the obtained genes, 114 genes were up-regulated and 133 were down-regulated. Based on the NCBI GenBank and Gene Ontology databases, most of these genes are involved in relevant cell functions such as metabolism, transport, translation, signal transduction and cell cycle. After quantitative PCR analysis, the observed underexpression of the selected genes could underlie the previously reported OA-induced cytoskeleton disruption, neurotransmission alterations and in vivo neurotoxic effects. The basal expression levels obtained at 48 h suggested that surviving cells were able to recover from OA-caused gene expression alterations. PMID:22284234

  19. Role of D-Limonene in Autophagy Induced by Bergamot Essential Oil in SH-SY5Y Neuroblastoma Cells

    PubMed Central

    Russo, Rossella; Cassiano, Maria Gilda Valentina; Ciociaro, Antonella; Adornetto, Annagrazia; Varano, Giuseppe Pasquale; Chiappini, Carlotta; Berliocchi, Laura; Tassorelli, Cristina; Bagetta, Giacinto; Corasaniti, Maria Tiziana

    2014-01-01

    Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a well characterized, widely used plant extract. BEO exerts anxiolytic, analgesic and neuroprotective activities in rodents through mechanisms that are only partly known and need to be further investigated. To gain more insight into the biological effects of this essential oil, we tested the ability of BEO (0.005–0.03%) to modulate autophagic pathways in human SH-SY5Y neuroblastoma cells. BEO-treated cells show increased LC3II levels and appearance of dot-like formations of endogenous LC3 protein that colocalize with the lysosome marker LAMP-1. Autophagic flux assay using bafilomycin A1 and degradation of the specific autophagy substrate p62 confirmed that the observed increase of LC3II levels in BEO-exposed cells is due to autophagy induction rather than to a decreased autophagosomal turnover. Induction of autophagy is an early and not cell-line specific response to BEO. Beside basal autophagy, BEO also enhanced autophagy triggered by serum starvation and rapamycin indicating that the underlying mechanism is mTOR independent. Accordingly, BEO did not affect the phosphorylation of ULK1 (Ser757) and p70S6K (Thr389), two downstream targets of mTOR. Furthermore, induction of autophagy by BEO is beclin-1 independent, occurs in a concentration-dependent manner and is unrelated to the ability of BEO to induce cell death. In order to identify the active constituents responsible for these effects, the two most abundant monoterpenes found in the essential oil, d-limonene (125–750 µM) and linalyl acetate (62.5–375 µM), were individually tested at concentrations comparable to those found in 0.005–0.03% BEO. The same features of stimulated autophagy elicited by BEO were reproduced by d-limonene, which rapidly increases LC3II and reduces p62 levels in a concentration-dependent manner. Linalyl acetate was ineffective in replicating BEO effects; however, it greatly enhanced LC3 lipidation triggered by d

  20. Role of D-Limonene in autophagy induced by bergamot essential oil in SH-SY5Y neuroblastoma cells.

    PubMed

    Russo, Rossella; Cassiano, Maria Gilda Valentina; Ciociaro, Antonella; Adornetto, Annagrazia; Varano, Giuseppe Pasquale; Chiappini, Carlotta; Berliocchi, Laura; Tassorelli, Cristina; Bagetta, Giacinto; Corasaniti, Maria Tiziana

    2014-01-01

    Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a well characterized, widely used plant extract. BEO exerts anxiolytic, analgesic and neuroprotective activities in rodents through mechanisms that are only partly known and need to be further investigated. To gain more insight into the biological effects of this essential oil, we tested the ability of BEO (0.005-0.03%) to modulate autophagic pathways in human SH-SY5Y neuroblastoma cells. BEO-treated cells show increased LC3II levels and appearance of dot-like formations of endogenous LC3 protein that colocalize with the lysosome marker LAMP-1. Autophagic flux assay using bafilomycin A1 and degradation of the specific autophagy substrate p62 confirmed that the observed increase of LC3II levels in BEO-exposed cells is due to autophagy induction rather than to a decreased autophagosomal turnover. Induction of autophagy is an early and not cell-line specific response to BEO. Beside basal autophagy, BEO also enhanced autophagy triggered by serum starvation and rapamycin indicating that the underlying mechanism is mTOR independent. Accordingly, BEO did not affect the phosphorylation of ULK1 (Ser757) and p70(S6K) (Thr389), two downstream targets of mTOR. Furthermore, induction of autophagy by BEO is beclin-1 independent, occurs in a concentration-dependent manner and is unrelated to the ability of BEO to induce cell death. In order to identify the active constituents responsible for these effects, the two most abundant monoterpenes found in the essential oil, d-limonene (125-750 µM) and linalyl acetate (62.5-375 µM), were individually tested at concentrations comparable to those found in 0.005-0.03% BEO. The same features of stimulated autophagy elicited by BEO were reproduced by D-limonene, which rapidly increases LC3II and reduces p62 levels in a concentration-dependent manner. Linalyl acetate was ineffective in replicating BEO effects; however, it greatly enhanced LC3 lipidation triggered by D

  1. P(VDF-TrFE)/BaTiO3 Nanoparticle Composite Films Mediate Piezoelectric Stimulation and Promote Differentiation of SH-SY5Y Neuroblastoma Cells.

    PubMed

    Genchi, Giada Graziana; Ceseracciu, Luca; Marino, Attilio; Labardi, Massimiliano; Marras, Sergio; Pignatelli, Francesca; Bruschini, Luca; Mattoli, Virgilio; Ciofani, Gianni

    2016-07-01

    Poly(vinylidene fluoride-trifluoroethylene, P(VDF-TrFE)) and P(VDF-TrFE)/barium titanate nanoparticle (BTNP) films are prepared and tested as substrates for neuronal stimulation through direct piezoelectric effect. Films are characterized in terms of surface, mechanical, and piezoelectric features before in vitro testing on SH-SY5Y cells. In particular, BTNPs significantly improve piezoelectric properties of the films (4.5-fold increased d31 ). Both kinds of films support good SH-SY5Y viability and differentiation. Ultrasound (US) stimulation is proven to elicit Ca(2+) transients and to enhance differentiation in cells grown on the piezoelectric substrates. For the first time in the literature, this study demonstrates the suitability of polymer/ceramic composite films and US for neuronal stimulation through direct piezoelectric effect. PMID:27283784

  2. Use of the Bruininks-Oseretsky Test of Motor Proficiency for Identifying Children with Motor Impairment

    ERIC Educational Resources Information Center

    Venetsanou, Fotini; Kambas, Antonis; Aggeloussis, Nickos; Serbezis, Vasilios; Taxildaris, Kyriakos

    2007-01-01

    This study compared the consistency of the Short Form (SF) and the Long Form (LF) of the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) in identifying preschool children with motor impairment (MI). One hundred and forty-four Greek preschool children participated (74 males, 70 females; mean age 5y 2mo [SD 5mo], range 4y 6mo-5y 6mo). Although…

  3. Involvement of diacylglycerol produced by phospholipase D activation in Aβ-induced reduction of sAPPα secretion in SH-SY5Y neuroblastoma cells.

    PubMed

    Tanabe, Fuminori; Nakajima, Tomoko; Ito, Masahiko

    2014-04-18

    We previously reported that the thiol proteinase inhibitor, E-64-d, ameliorated amyloid β (Aβ)-induced reduction of soluble amyloid precursor protein α (sAPPα) secretion by reversing ceramide-induced protein kinase C down-regulation in SH-SY5Y neuroblastoma cells. In the present study, we showed that Aβ (1-42) peptide enhanced diacylglycerol (DAG) production by phospholipase D (PLD) activation in these cells. We subsequently examined whether PLD was involved in Aβ-induced reduction of sAPPα secretion and showed that 2 μM CAY10593, which selectively inhibits PLD2, ameliorated reduction of sAPPα secretion, whereas 50 nM CAY10593, which selectively inhibits PLD1, did not. Moreover, 50 µM propranolol, a phosphatidic acid phosphohydrolase inhibitor, also ameliorated Aβ-induced reduction of sAPPα secretion, suggesting that DAG may be responsible for Aβ-induced reduction of sAPPα. We subsequently examined whether DAG affects sAPPα secretion and showed that a DAG analog reduced sAPPα secretion in SH-SY5Y cells. In addition, DAG enhanced ceramide production by stimulating neutral sphingomyelinase (N-SMase) activity. We previously demonstrated that Aβ stimulates N-SMase activity in SH-SY5Y cells. Here, we showed that inhibition of PLD2 by 2 μM CAY10593 suppressed Aβ-induced N-SMase activation. Taken together, the results suggest that DAG produced through the PLD pathway is involved in Aβ-induced reduction of sAPPα secretion in SH-SY5Y cells. PMID:24650665

  4. Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway

    PubMed Central

    Cui, Zhen-wen; Xie, Zheng-xing; Wang, Bao-feng; Zhong, Zhi-hong; Chen, Xiao-yan; Sun, Yu-hao; Sun, Qing-fang; Yang, Guo-yuan; Bian, Liu-guan

    2015-01-01

    Aim: Carvacrol (2-methyl-5-isopropylphenol), a phenolic monoterpene in the essential oils of the genera Origanum and Thymus, has been shown to exert a variety of therapeutic effects. Here we examined whether carvacrol protected neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis and explored the underlying mechanisms. Methods: Neuroblastoma SH-SY5Y cells were incubated with Fe2+ for 24 h, and the cell viability was assessed with CCK-8 assay. TUNEL assay and flow cytometric analysis were performed to evaluate cell apoptosis. The mRNA levels of pro-inflammatory cytokines and NF-κB p65 were determined using qPCR. The expression of relevant proteins was determined using Western blot analysis or immunofluorescence staining. Results: Treatment of SH-SY5Y cells with Fe2+ (50–200 μmol/L) dose-dependently decreased the cell viability, which was significantly attenuated by pretreatment with carvacrol (164 and 333 μmol/L). Treatment with Fe2+ increased the Bax level and caspase-3 activity, and decreased the Bcl-2 level, resulting in cell apoptosis. Furthermore, treatment with Fe2+ significantly increased the gene expression of IL-1β, IL-6 and TNF-α, and induced the nuclear translocation of NF-κB. Treatment with Fe2+ also significantly increased the phosphorylation of p38, ERK, JNK and IKK in the cells. Pretreatment with carvacrol significantly inhibited Fe2+-induced activation of NF-κB, expression of the pro-inflammatory cytokines, and cell apoptosis. Moreover, pretreatment with carvacrol inhibited Fe2+-induced phosphorylation of JNK and IKK, but not p38 and ERK in the cells. Conclusion: Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis, which may result from suppressing the MAPK/JNK-NF-κB signaling pathways. PMID:26592517

  5. Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity.

    PubMed

    Jing, X; Shi, H; Zhang, C; Ren, M; Han, M; Wei, X; Zhang, X; Lou, H

    2015-02-12

    Oxidative stress is central to the pathology of several neurodegenerative diseases, including Parkinson's disease (PD), and therapeutics designed to enhance antioxidant potential could have clinical value. In this study, we investigated whether dimethyl fumarate (DMF) has therapeutic effects in cellular and animal model of PD, and explore the role of nuclear transcription factor related to NF-E2 (Nrf2) in this process. Treatment of animals and dopaminergic SH-SY5Y cells with DMF resulted in increased nuclear levels of active Nrf2, with subsequent upregulation of antioxidant target genes. The cytotoxicity of 6-hydroxydopamine (6-OHDA) was reduced by pre-treatment with DMF in SH-SY5Y cells. The increase in the reactive oxygen species caused by 6-OHDA treatment was also attenuated by DMF in SH-SY5Y cells. The neuroprotective effects of DMF against 6-OHDA neurotoxicity were dependent on Nrf2, since treatment with Nrf2 siRNA failed to block against 6-OHDA neurotoxicity and induce Nrf2-dependent cytoprotective genes in SH-SY5Y cells. In vivo, DMF oral administration was shown to upregulate mRNA and protein levels of Nrf2 and Nrf2-regulated cytoprotective genes, attenuate 6-OHDA induced striatal oxidative stress and inflammation in C57BL/6 mice. Moreover, DMF ameliorated dopaminergic neurotoxicity in 6-OHDA-induced PD animal models as evidenced by amelioration of locomotor dysfunction, loss in striatal dopamine, and reductions in dopaminergic neurons in the substantia nigra and striatum. Taken together, these data strongly suggest that DMF may be beneficial for the treatment of neurodegenerative diseases like PD. PMID:25449120

  6. Phosphorylation of Amyloid Precursor Protein at Threonine 668 Is Essential for Its Copper-responsive Trafficking in SH-SY5Y Neuroblastoma Cells*

    PubMed Central

    Acevedo, Karla M.; Opazo, Carlos M.; Norrish, David; Challis, Leesa M.; Li, Qiao-Xin; White, Anthony R.; Bush, Ashley I.; Camakaris, James

    2014-01-01

    Amyloid precursor protein (APP) undergoes post-translational modification, including O- and N-glycosylation, ubiquitination, and phosphorylation as it traffics through the secretory pathway. We have previously reported that copper promotes a change in the cellular localization of APP. We now report that copper increases the phosphorylation of endogenous APP at threonine 668 (Thr-668) in SH-SY5Y neuronal cells. The level of APPT668-p (detected using a phospho-site-specific antibody) exhibited a copper-dependent increase. Using confocal microscopy imaging we demonstrate that the phospho-deficient mutant, Thr-668 to alanine (T668A), does not exhibit detectable copper-responsive APP trafficking. In contrast, mutating a serine to an alanine at residue 655 does not affect copper-responsive trafficking. We further investigated the importance of the Thr-668 residue in copper-responsive trafficking by treating SH-SY5Y cells with inhibitors for glycogen synthase kinase 3-β (GSK3β) and cyclin-dependent kinases (Cdk), the main kinases that phosphorylate APP at Thr-668 in neurons. Our results show that the GSK3β kinase inhibitors LiCl, SB 216763, and SB 415286 prevent copper-responsive APP trafficking. In contrast, the Cdk inhibitors Purvalanol A and B had no significant effect on copper-responsive trafficking in SH-SY5Y cells. In cultured primary hippocampal neurons, copper promoted APP re-localization to the axon, and this effect was inhibited by the addition of LiCl, indicating that a lithium-sensitive kinase(s) is involved in copper-responsive trafficking in hippocampal neurons. This is consistent with APP axonal transport to the synapse, where APP is involved in a number of functions. We conclude that copper promotes APP trafficking by promoting a GSK3β-dependent phosphorylation in SH-SY5Y cells. PMID:24610780

  7. Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

    PubMed

    Lopez, Elizabeth F; Kabarowski, Janusz H; Ingle, Kevin A; Kain, Vasundhara; Barnes, Stephen; Crossman, David K; Lindsey, Merry L; Halade, Ganesh V

    2015-02-15

    Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3-5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P<0.05). Macrophage inflammatory protein-1γ and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P<0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-lipoxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators. PMID:25485899

  8. Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction

    PubMed Central

    Lopez, Elizabeth F.; Kabarowski, Janusz H.; Ingle, Kevin A.; Kain, Vasundhara; Barnes, Stephen; Crossman, David K.; Lindsey, Merry L.

    2014-01-01

    Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3–5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P < 0.05). Macrophage inflammatory protein-1γ and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P < 0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-lipoxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators. PMID:25485899

  9. The mechanism of action of FXR1P-related miR-19b-3p in SH-SY5Y.

    PubMed

    Ma, Yun; Tian, Shuai; He, Shuya; Chen, Qiong; Wang, Zongbao; Xiao, Xiao; Fu, Liang; Lei, Xiaoyong

    2016-08-15

    The biological effects of microRNAs (miRNAs) in the Fragile X Syndrome (FXS) have been widely studied. Dysregulation of miRNAs plays a critical role in the progression of nervous system diseases and in cell proliferation and differentiation. Our previous study validated that miR-19b-3p was associated with FXR1 (Fragile X related gene 1), one of homologous genes of FMR1 (Fragile X mental retardation 1). The purpose of this study was to investigate the relationship of FXR1 and miR-19b-3p, and the crucial role of miR-19b-3p in FXS and to validate whether miR-19b-3p could regulate the growth of SH-SY5Y cells. We determined that miR-19b-3p could regulate the expression of not only USP32, RAB18 and Dusp6 but also FXR1, and FXR1 could in turn regulate the expression of miR-19b-3p. What's more, the overexpression of miR-19b-3p significantly inhibited the proliferation, contributed the apoptosis and slowed down the cycle of SH-SY5Y cells. Taken together, our results indicate that miR-19b-3p plays a significant role in the molecular pathology of FXS by interacting with FXR1 and influencing the growth of SH-SY5Y cells. PMID:27138803

  10. Diclofenac-Induced Apoptosis in the Neuroblastoma Cell Line SH-SY5Y: Possible Involvement of the Mitochondrial Superoxide Dismutase

    PubMed Central

    Cecere, Francesca; Iuliano, Annarita; Albano, Francesco; Zappelli, Claudia; Castellano, Immacolata; Grimaldi, Pasquale; Masullo, Mariorosario; De Vendittis, Emmanuele; Ruocco, Maria Rosaria

    2010-01-01

    Diclofenac, a nonsteroidal anti-inflammatory drug, induces apoptosis on the neuroblastoma cell line SH-SY5Y through a mitochondrial dysfunction, affecting some antioxidant mechanisms. Indeed, the time- and dose-dependent increase of apoptosis is associated to an early enhancement of the reactive oxygen species (ROS). Mitochondrial superoxide dismutase (SOD2) plays a crucial role in the defence against ROS, thus protecting against several apoptotic stimuli. Diclofenac decreased the protein levels and the enzymatic activity of SOD2, without any significant impairment of the corresponding mRNA levels in the SH-SY5Y extracts. When cells were incubated with an archaeal exogenous thioredoxin, an attenuation of the diclofenac-induced apoptosis was observed, together with an increase of SOD2 protein levels. Furthermore, diclofenac impaired the mitochondrial membrane potential, leading to a release of cytochrome c. These data suggest that mitochondria are involved in the diclofenac-induced apoptosis of SH-SY5Y cells and point to a possible role of SOD2 in this process. PMID:20625417

  11. Protective role of olesoxime against wild-type α-synuclein-induced toxicity in human neuronally differentiated SHSY-5Y cells

    PubMed Central

    Gouarné, C; Tracz, J; Paoli, M Giraudon; Deluca, V; Seimandi, M; Tardif, G; Xilouri, M; Stefanis, L; Bordet, T; Pruss, R M

    2015-01-01

    BACKGROUND AND PURPOSE Parkinson's disease (PD) is usually diagnosed clinically from classical motor symptoms, while definitive diagnosis is made postmortem, based on the presence of Lewy bodies and nigral neuron cell loss. α-Synuclein (ASYN), the main protein component of Lewy bodies, clearly plays a role in the neurodegeneration that characterizes PD. Additionally, mutation in the SNCA gene or copy number variations are associated with some forms of familial PD. Here, the objective of the study was to evaluate whether olesoxime, a promising neuroprotective drug can prevent ASYN-mediated neurotoxicity. EXPERIMENTAL APPROACH We used here a novel, mechanistically approachable and attractive cellular model based on the inducible overexpression of human wild-type ASYN in neuronally differentiated human neuroblastoma (SHSY-5Y) cells. This model demonstrates gradual cellular degeneration, coinciding temporally with the appearance of soluble and membrane-bound ASYN oligomers and cell death combining both apoptotic and non-apoptotic pathways. KEY RESULTS Olesoxime fully protected differentiated SHSY-5Y cells from cell death, neurite retraction and cytoplasmic shrinkage induced by moderate ASYN overexpression. This protection was associated with a reduction in cytochrome c release from mitochondria and caspase-9 activation suggesting that olesoxime prevented ASYN toxicity by preserving mitochondrial integrity and function. In addition, olesoxime displayed neurotrophic effects on neuronally differentiated SHSY-5Y cells, independent of ASYN expression, by promoting their differentiation. CONCLUSIONS AND IMPLICATIONS Because ASYN is a common underlying factor in many cases of PD, olesoxime could be a promising therapy to slow neurodegeneration in PD. PMID:25220617

  12. Protection of seven dibenzocyclooctadiene lignans from Schisandra chinensis against serum and glucose deprivation injury in SH-SY5Y cells.

    PubMed

    E, Qun; Tang, Miao; Zhang, XiaoChuan; Shi, YunWei; Wang, DanDan; Gu, Yun; Li, ShiYing; Liang, XinMiao; Wang, ZhiWei; Wang, CaiPing

    2015-12-01

    Dibenzocyclooctadiene lignans, the major active components of fruit of Schisandra chinensis (Turcz.) Baill., have been found to have activities that could prevent prostate and thyroid cancer, hepatotoxicity, oxidative stress-induced cerebral injury, etc. This study was conducted to evaluate the effects of seven dibenzocyclooctadiene lignans of Schisandra chinensis and explore the possible mechanisms in the human neuroblastoma SH-SY5Y cells exposed on serum and glucose deprivation (SGD) injury. The structure-activity relationships were also analyzed. Cell viability and lactate dehydrogenase (LDH) release were determined to evaluate cell injury. Inflammation and apoptosis-related protein levels were detected to elucidate the possible mechanisms. Schisantherin A, schizandrin C, and schizandrol B were found to have stronger protective effects than schizandrin A, schizandrin B, and schisanhenol in SH-SY5Y cells against SGD injury. Moreover, the protective effects of these lignans were possibly exhibited by regulating inflammation and apoptosis-related proteins in SH-SY5Y cells after SGD injury, supporting their beneficial effects for the prevention of cell injury in the pathogenesis of the central nervous system diseases, including ischemia stroke. The number and position of hydroxyl group and methylenedioxy in these lignans may be required for their effects. PMID:26289388

  13. Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

    PubMed Central

    Khwanraj, Kawinthra; Phruksaniyom, Chareerut; Madlah, Suriyat; Dharmasaroja, Permphan

    2015-01-01

    The human neuroblastoma SH-SY5Y cell line has been used as a dopaminergic cell model for Parkinson's disease research. Whether undifferentiated or differentiated SH-SY5Y cells are more suitable remains controversial. This study aims to evaluate the expression of apoptosis-related mRNAs activated by MPP+ and evaluate the differential expression of tyrosine hydroxylase (TH) in undifferentiated and retinoic acid- (RA-) induced differentiated cells. The western blot results showed a gradual decrease in TH in undifferentiated cells and a gradual increase in TH in differentiated cells from days 4 to 10 after cell plating. Immunostaining revealed a gradual increase in TH along with neuritic outgrowth in differentiated cells on days 4 and 7 of RA treatment. For the study on cell susceptibility to MPP+ and the expression of apoptosis-related genes, MTT assay showed a decrease in cell viability to approximately 50% requiring 500 and 1000 μM of MPP+ for undifferentiated and RA-differentiated cells, respectively. Using real-time RT-PCR, treatment with 500 μM MPP+ led to significant increases in the Bax/Bcl-2 ratio, p53, and caspase-3 in undifferentiated cells but was without significance in differentiated cells. In conclusion, differentiated cells may be more suitable, and the shorter duration of RA differentiation may make the SH-SY5Y cell model more accessible. PMID:26634154

  14. Acrylamide affects proliferation and differentiation of the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y.

    PubMed

    Attoff, K; Kertika, D; Lundqvist, J; Oredsson, S; Forsby, A

    2016-09-01

    Acrylamide is a well-known neurotoxic compound and people get exposed to the compound by food consumption and environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed resulting in a risk for developmental neurotoxicity. In this study, the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as alerting indicators for developmental neurotoxicity. For both cell lines, acrylamide reduced the number of viable cells by reducing proliferation and inducing cell death in undifferentiated cells. Acrylamide concentrations starting at 10fM attenuated the differentiation process in SH-SY5Y cells by sustaining cell proliferation and neurite outgrowth was reduced at concentrations from 10pM. Acrylamide significantly reduced the number of neurons starting at 1μM and altered the ratio between the different phenotypes in differentiating C17.2 cell cultures. Ten micromolar of acrylamide also reduced the expression of the neuronal and astrocyte biomarkers. Although the neurotoxic concentrations in the femtomolar range seem to be specific for the SH-SY5Y cell line, the fact that micromolar concentrations of acrylamide seem to attenuate the differentiation process in both cell lines raises the interest to further investigations on the possible developmental neurotoxicity of acrylamide. PMID:27241584

  15. Role for the PI3K/Akt/Nrf2 signaling pathway in the protective effects of carnosic acid against methylglyoxal-induced neurotoxicity in SH-SY5Y neuroblastoma cells.

    PubMed

    de Oliveira, Marcos Roberto; Ferreira, Gustavo Costa; Schuck, Patrícia Fernanda; Dal Bosco, Simone Morelo

    2015-12-01

    Glycation, a process that occurs endogenously and generates advanced glycation end products (AGEs), presents an important role in cases of neurodegeneration, as for instance Alzheimer's disease (AD). Methylglyoxal (MG), a dicarbonyl compound, is the most potent inducer of AGEs, whose levels have been found increased in samples obtained from subjects suffering from AD. Moreover, MG induces protein cross-linking and redox impairment in vitro and in vivo. Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, exerts protective effects in neuronal cells by increasing antioxidant defenses and detoxification systems. In the present work, we aimed to investigate whether there is a role for CA against MG-induced neurotoxicity. Data obtained here clearly demonstrate that CA pretreatment (1 μM for 12 h) caused cytoprotective effects and counteracted the damage elicited by MG in SH-SY5Y cells. CA inhibited loss of mitochondrial membrane polarity (MMP) and cytochrome c release from mitochondria, consequently blocking activation of pro-apoptotic caspase enzymes. Furthermore, CA alleviated MG-induced oxidative and nitrosative damage. CA prevented MG-dependent neurotoxicity by activating the PI3K/Akt/Nrf2 signaling pathway and the antioxidant enzymes modulated by Nrf2 transcription factor. Overall, the data presented here show the protective role of CA by its ability to counteract MG negative effects. PMID:26577515

  16. Growth Failure in Children with Intractable Epilepsy Is Not Due to Increased Resting Energy Expenditure

    ERIC Educational Resources Information Center

    Bergqvist, A. G. Christina; Trabulsi, Jillian; Schall, Joan I.; Stallings, Virginia A.

    2008-01-01

    The aim of this study was to evaluate the resting energy expenditure (REE) of children with intractable epilepsy (IE) compared with healthy children, and to determine factors that contribute to the pattern of REE. REE, growth status, and body composition were assessed in 25 prepubertal children with IE (15 males, 10 females; mean age 5y 5mo [SD 2y…

  17. Autoimmune Diseases in Parents of Children with Infantile Autism: A Case--Control Study

    ERIC Educational Resources Information Center

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben; Nedergaard, Niels Jorgen

    2007-01-01

    This register study compared the rates and types of autoimmune disease in the parents of 111 patients (82 males, 29 females; mean age at diagnosis 5y 5mo [SD 2y 6mo]) with infantile autism (IA) with a matched control group of parents of 330 children from the general population. All parents were screened through the nationwide Danish National…

  18. Description of 3,180 Courses of Chelation with Dimercaptosuccinic Acid in Children ≤5 y with Severe Lead Poisoning in Zamfara, Northern Nigeria: A Retrospective Analysis of Programme Data

    PubMed Central

    Thurtle, Natalie; Greig, Jane; Cooney, Lauren; Amitai, Yona; Ariti, Cono; Brown, Mary Jean; Kosnett, Michael J.; Moussally, Krystel; Sani-Gwarzo, Nasir; Akpan, Henry; Shanks, Leslie; Dargan, Paul I.

    2014-01-01

    Background In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤5 y of age with severe paediatric lead intoxication reported to date to our knowledge. Methods and Findings In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%–79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%–57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine

  19. Manganese-induced oxidative DNA damage in neuronal SH-SY5Y cells: attenuation of thymine base lesions by glutathione and N-acetylcysteine.

    PubMed

    Stephenson, Adrienne P; Schneider, Jeffrey A; Nelson, Bryant C; Atha, Donald H; Jain, Ashok; Soliman, Karam F A; Aschner, Michael; Mazzio, Elizabeth; Renee Reams, R

    2013-04-26

    Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson's disease (IPD). Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns. The underlying mechanism of Mn neurotoxicity remains unclear. Accordingly, the present study was designed to investigate the toxic effects of Mn(2+) in human neuroblastoma SH-SY5Y cells. Mn(2+) caused a concentration dependent decrease in SH-SY5Y cellular viability compared to controls. The LD50 value was 12.98 μM Mn(2+) (p<0.001 for control vs. 24h Mn treatment). Both TUNEL and annexin V/propidium iodide (PI) apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn(2+) (2 μM, 62 μM or 125 μM). In addition, Mn(2+) induced both the formation and accumulation of DNA single strand breaks (via alkaline comet assay analysis) and oxidatively modified thymine bases (via gas chromatography/mass spectrometry analysis). Pre-incubation of the cells with characteristic antioxidants, either 1mM N-acetylcysteine (NAC) or 1mM glutathione (GSH) reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage. Our findings indicate that (1) exposure of SH-SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA damage, (2) SH-SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and (3) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants. This is the first known report of Mn(2+)-induction and antioxidant protection of thymine lesions in this SH-SY5Y cell line and contributes new information to the potential use of antioxidants

  20. Ferulic Acid Regulates the Nrf2/Heme Oxygenase-1 System and Counteracts Trimethyltin-Induced Neuronal Damage in the Human Neuroblastoma Cell Line SH-SY5Y

    PubMed Central

    Catino, Stefania; Paciello, Fabiola; Miceli, Fiorella; Rolesi, Rolando; Troiani, Diana; Calabrese, Vittorio; Santangelo, Rosaria; Mancuso, Cesare

    2016-01-01

    Over the past years, several lines of evidence have pointed out the efficacy of ferulic acid (FA) in counteracting oxidative stress elicited by β-amyloid or free radical initiators, based on the ability of this natural antioxidant to up-regulate the heme oxygenase-1 (HO-1) and biliverdin reductase (BVR) system. However, scarce results can be found in literature regarding the cytoprotective effects of FA in case of damage caused by neurotoxicants. The aim of this work is to investigate the mechanisms through which FA exerts neuroprotection in SH-SY5Y neuroblastoma cells exposed to the neurotoxin trimethyltin (TMT). FA (1–10 μM for 6 h) dose-dependently increased both basal and TMT (10 μM for 24 h)-induced HO-1 expression in SH-SY5Y cells by fostering the nuclear translocation of the transcriptional activator Nrf2. In particular, the co-treatment of FA (10 μM) with TMT was also responsible for the nuclear translocation of HO-1 in an attempt to further increase cell stress response in SH-SY5Y cells. In addition to HO-1, FA (1–10 μM for 6 h) dose-dependently increased the basal expression of BVR. The antioxidant and neuroprotective features of FA, through the increase of HO activity, were supported by the evidence that FA inhibited TMT (10 μM)-induced lipid peroxidation (evaluated by detecting 4-hydroxy-nonenal) and DNA fragmentation in SH-SY5Y cells and that this antioxidant effect was reversed by the HO inhibitor Zinc-protoporphyrin-IX (5 μM). Among the by-products of the HO/BVR system, carbon monoxide (CORM-2, 50 nM) and bilirubin (BR, 50 nM) significantly inhibited TMT-induced superoxide anion formation in SH-SY5Y cells. All together, these results corroborate the neuroprotective effect of FA through the up-regulation of the HO-1/BVR system, via carbon monoxide and BR formation, and provide the first evidence on the role of HO-1/Nrf2 axis in FA-related enhancement of cell stress response in human neurons. PMID:26779023

  1. A fluorescence assay for measuring acetylcholinesterase activity in rat blood and a human neuroblastoma cell line (SH-SY5Y).

    PubMed

    Santillo, Michael F; Liu, Yitong

    2015-01-01

    Acetylcholinesterase (AChE) is an enzyme responsible for metabolism of the neurotransmitter acetylcholine, and inhibition of AChE can have therapeutic applications (e.g., drugs for Alzheimer's disease) or neurotoxic consequences (e.g., pesticides). A common absorbance-based AChE activity assay that uses 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) can have limited sensitivity and be prone to interference. Therefore, an alternative assay was developed, in which AChE activity was determined by measuring fluorescence of resorufin produced from coupled enzyme reactions involving acetylcholine and Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine). The Amplex Red assay was used for two separate applications. First, AChE activity was measured in rat whole blood, which is a biomarker for exposure to AChE inhibitor pesticides. Activity was quantified from a 10(5)-fold dilution of whole blood, and there was a linear correlation between Amplex Red and DTNB assays. For the second application, Amplex Red assay was used to measure AChE inhibition potency in a human neuroblastoma cell line (SH-SY5Y), which is important for assessing pharmacological and toxicological potential of AChE inhibitors including drugs, phytochemicals, and pesticides. Five known reversible inhibitors were evaluated (IC50, 7-225 nM), along with irreversible inhibitors chlorpyrifos-oxon (ki=1.01 nM(-1)h(-1)) and paraoxon (ki=0.16 nM(-1)h(-1)). Lastly, in addition to inhibition, AChE reactivation was measured in SH-SY5Y cells incubated with pralidoxime chloride (2-PAM). The Amplex Red assay is a sensitive, specific, and reliable fluorescence method for measuring AChE activity in both rat whole blood and cultured SH-SY5Y cells. PMID:26165232

  2. Paullinia cupana Mart. var. Sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity.

    PubMed

    de Oliveira, Diêgo Madureira; Barreto, George; Galeano, Pablo; Romero, Juan Ignacio; Holubiec, Mariana Inés; Badorrey, Maria Sol; Capani, Francisco; Alvarez, Lisandro Diego Giraldez

    2011-09-01

    Paullinia cupana Mart. var. Sorbilis, commonly known as Guaraná, is a Brazilian plant frequently cited for its antioxidant properties and different pharmacological activities on the central nervous system. The potential beneficial uses of Guaraná in neurodegenerative disorders, such as in Parkinson's disease (PD), the pathogenesis of which is associated with mitochondrial dysfunction and oxidative stress, has not yet been assessed. Therefore, the main aim of the present study was to evaluate if an extract of commercial powdered seeds of Guaraná could protect human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Two concentration of Guaraná dimethylsulfoxide extract (0.312 and 0.625 mg/mL) were added to SH-SY5Y cells treated with 300 nM rotenone for 48 h, and the cytoprotective effects were assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, measuring lactate dehydrogenase (LDH) levels, and analyzing nuclear integrity with Hoechst33258 stain. Results showed that the addition of Guaraná extract significantly increased the cell viability of SH-SY5Y cells treated with rotenone, in a dose-dependent manner. On the other hand, LDH levels were significantly reduced by addition of 0.312 mg/mL of Guaraná, but unexpectedly, no changes were observed with the higher concentration. Moreover, chromatin condensation and nuclear fragmentation were significantly reduced by addition of any of both concentrations of the extract. The results obtained in this work could provide relevant information about the mechanisms underlying the degeneration of dopaminergic neurons in PD and precede in vivo experiments. Further studies are needed to investigate which active constituent is responsible for the cytoprotective effect produced by Paullinia cupana. PMID:21081703

  3. The Neuroprotective Effect of Erythropoietin on Rotenone-Induced Neurotoxicity in SH-SY5Y Cells Through the Induction of Autophagy.

    PubMed

    Jang, Wooyoung; Kim, Hee Ju; Li, Huan; Jo, Kwang Deog; Lee, Moon Kyu; Yang, Hyun Ok

    2016-08-01

    Currently, the autophagy pathway is thought to be important for the pathogenesis of Parkinson's disease (PD), and the modulation of autophagy may be a novel strategy for the treatment of this disease. Erythropoietin (EPO) has been reported to have neuroprotective effects through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms, and it has also been shown to modulate autophagy signaling in an oxygen toxicity model. Therefore, we investigated the effects of EPO on autophagy markers and evaluated its neuroprotective effect on rotenone-induced neurotoxicity. We adapted the rotenone-induced neurotoxicity model to SH-SY5Y cells as an in vitro model of PD. We measured cell viability using MTT and annexin V/propidium iodide assays and measured intracellular levels of reactive oxygen species. Immunofluorescence analysis was performed to measure the expression of LC3 and α-synuclein. Intracellular signaling proteins associated with autophagy were examined by immunoblot analysis. EPO mono-treatment increased the levels of mammalian target of rapamycin (mTOR)-independent/upstream autophagy markers, including Beclin-1, AMPK, and ULK-1. Rotenone treatment of SH-SY5Y cells reduced their viability, increased reactive oxygen species levels, and induced apoptosis and α-synuclein expression, and simultaneous exposure to EPO significantly reduced these effects. Rotenone enhanced mTOR expression and suppressed Beclin-1 expression, indicating suppression of the autophagy system. However, combined treatment with EPO restored Beclin-1 expression and decreased mTOR expression. EPO protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy-related signaling pathways. The experimental evidence for the EPO-induced neuroprotection against rotenone-induced dopaminergic neurotoxicity may significantly impact the development of future PD treatment strategies. PMID:26156288

  4. Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress.

    PubMed

    Schneider, Lonnie; Giordano, Samantha; Zelickson, Blake R; S Johnson, Michelle; A Benavides, Gloria; Ouyang, Xiaosen; Fineberg, Naomi; Darley-Usmar, Victor M; Zhang, Jianhua

    2011-12-01

    Cell differentiation is associated with changes in metabolism and function. Understanding these changes during differentiation is important in the context of stem cell research, cancer, and neurodegenerative diseases. An early event in neurodegenerative diseases is the alteration of mitochondrial function and increased oxidative stress. Studies using both undifferentiated and differentiated SH-SY5Y neuroblastoma cells have shown distinct responses to cellular stressors; however, the mechanisms remain unclear. We hypothesized that because the regulation of glycolysis and oxidative phosphorylation is modulated during cellular differentiation, this would change bioenergetic function and the response to oxidative stress. To test this, we used retinoic acid (RA) to induce differentiation of SH-SY5Y cells and assessed changes in cellular bioenergetics using extracellular flux analysis. After exposure to RA, the SH-SY5Y cells had an increased mitochondrial membrane potential, without changing mitochondrial number. Differentiated cells exhibited greater stimulation of mitochondrial respiration with uncoupling and an increased bioenergetic reserve capacity. The increased reserve capacity in the differentiated cells was suppressed by the inhibitor of glycolysis 2-deoxy-d-glucose. Furthermore, we found that differentiated cells were substantially more resistant to cytotoxicity and mitochondrial dysfunction induced by the reactive lipid species 4-hydroxynonenal or the reactive oxygen species generator 2,3-dimethoxy-1,4-naphthoquinone. We then analyzed the levels of selected mitochondrial proteins and found an increase in complex IV subunits, which we propose contributes to the increase in reserve capacity in the differentiated cells. Furthermore, we found an increase in MnSOD that could, at least in part, account for the increased resistance to oxidative stress. Our findings suggest that profound changes in mitochondrial metabolism and antioxidant defenses occur upon

  5. Inhibition of beta-amyloid-induced neurotoxicity by pinocembrin through Nrf2/HO-1 pathway in SH-SY5Y cells.

    PubMed

    Wang, Yumin; Miao, Yingchun; Mir, Aamina Zia; Cheng, Long; Wang, Lina; Zhao, Linan; Cui, Qifu; Zhao, Weili; Wang, Hongquan

    2016-09-15

    Amyloid beta peptide (Aβ) can cause neurotoxicity in Alzheimer's disease (AD). It evokes a cascade of oxidative damage to neurons. Pinocembrin (PCB), the most abundant flavonoid in propolis, has been proven to have neuroprotective effects in vivo and in vitro. In the present study, we investigated the neuroprotective effects of PCB on Aβ25-35-induced neurotoxicity. Exposure of SH-SY5Y cells to 25μM Aβ25-35 for 24h caused viability loss, apoptotic increase and reactive oxygen species (ROS) increase, pre-treatment with PCB for 4h significantly reduced the viability loss, apoptotic rate and attenuated Aβ-mediated ROS production. PCB strikingly inhibited Aβ25-35-induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio. In addition, PCB suppressed the release of cytochrome c and the cleavage of caspase-3. PCB treatment also resulted in an increase in Nrf2 protein levels and subsequent induction of heme oxygenase-1(HO-1) expression in SH-SY5Y cells. RNA interference-mediated knockdown of Nrf2 expression suppressed the PCB-induced HO-1 expression. Notably, we found that the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) markedly diminished the neuroprotective effect of PCB against Aβ-mediated neurotoxicity. Taken together, these results indicated that PCB protects SH-SY5Y cells from Aβ25-35-induced neurotoxicity through activation of Nrf2/HO-1 pathways. Thus, activation of Nrf2/HO-1 pathways and inhibition of mitochondria-dependent apoptosis together may protect cells from Aβ25-35-induceded neurotoxicity. PMID:27538638

  6. N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma cell line and sensitizes it to chemotherapeutic agents.

    PubMed

    Mazzoccoli, Carmela; Ruggieri, Vitalba; Tataranni, Tiziana; Agriesti, Francesca; Laurenzana, Ilaria; Fratello, Angelo; Capitanio, Nazzareno; Piccoli, Claudia

    2016-05-01

    Neuroblastoma is the most commonly extra-cranial solid tumor of childhood frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the most abundant metabolites present in the central nervous system (CNS) and appears to be involved in many CNS disorders. The functional significance of the high NAA concentration in the brain remains uncertain, but it confers to NAA a unique clinical significance exploited in magnetic resonance spectroscopy. In the current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This effect is partly due to enhanced apoptosis, shown by decrease of the anti-apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle progression, linked to enhanced expression of the cyclin-inhibitors p53, p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited morphological changes accompanied with increase of the neurogenic markers TH and MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184. Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our knowledge, this is the first study demonstrating the neuronal differentiating effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. PMID:27036033

  7. Expression of URG4/URGCP, Cyclin D1, Bcl-2, and Bax genes in retinoic acid treated SH-SY5Y human neuroblastoma cells

    PubMed Central

    Gundogdu, Gulsah; Koc, Tugba; Yonguc, G. Nilufer; Kucukatay, Vural; Satiroglu-Tufan, N. Lale

    2013-01-01

    Retinoic acid (RA) plays important roles in development, growth, and differentiation by regulating the expression of its target genes. The pro-apoptotic Bax gene may form channels through oligomerization in the mitochondrial membrane and facilitate the cytosolic release of cytochrome c. The anti-apoptotic Bcl-2 gene can inhibit this process. Up-regulated gene 4/Upregulator of cell proliferation (URG4/URGCP) is a novel gene located on 7p13. URG4/URGCP also stimulates cyclin D1 (CCND1) mRNA expression, and RNAi-mediated URG4/URGCP silencing diminishes CCND1 mRNA expression in HepG2 cells. In this study, the effects of RA treatment on URG4/URGCP, CCND1, Bcl-2 and Bax gene expression changes in undifferentiated and differentiated SHSY5Y neuroblastoma cells was analyzed. SHSY5Y cells were cultured in the appropriate conditions. To induce differentiation, the cells were treated with 10 micromolar RA in the dark for 3-10 days. SHSY5Y cells possess small processes in an undifferentiated state, and after treatment with RA, the cells developed long neurites, resembling a neuronal phenotype. Total RNA was isolated with Tri-Reagent. Expression profiles of the target genes were determined by semi-quantitative RT-PCR. According to the results, Bcl-2 and CCND1 gene expression levels were increased, while URG4/URGCP and Bax gene expression was decreased in RA treated cells compared to the control cells. Our preliminary results suggest that RA may induce cell proliferation and escape apoptosis using a novel pathway by the URG4/URGCP gene. Further investigations are needed to clarify more direct transcriptional targets of RA signaling and the interaction of RA pathways with other pro-regenerative signals. PMID:24592121

  8. MLIF Alleviates SH-SY5Y Neuroblastoma Injury Induced by Oxygen-Glucose Deprivation by Targeting Eukaryotic Translation Elongation Factor 1A2

    PubMed Central

    Liu, Yulan; Cheng, Hao; Wang, Jing; Zhang, Yue; Rui, Yaocheng; Li, Tiejun

    2016-01-01

    Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide, has been shown to exert potent anti-inflammatory effects in ischemic brain injury. In this study, we investigated the neuroprotective action of MLIF against oxygen-glucose deprivation (OGD)-induced injury in human neuroblastoma SH-SY5Y cells. MTT assay was used to assess cell viability, and flow cytometry assay and Hoechst staining were used to evaluate apoptosis. LDH assay was used to exam necrosis. The release of inflammatory cytokines was detected by ELISA. Levels of the apoptosis associated proteins were measured by western blot analysis. To identify the protein target of MLIF, pull-down assay and mass spectrometry were performed. We observed that MLIF enhanced cell survival and inhibited apoptosis and necrosis by inhibiting p-JNK, p53, c-caspase9 and c-caspase3 expression. In the microglia, OGD-induced secretion of inflammatory cytokines was markedly reduced in the presence of MLIF. Furthermore, we found that eukaryotic translation elongation factor 1A2 (eEF1A2) is a downstream target of MLIF. Knockdown eEF1A2 using short interfering RNA (siRNA) almost completely abrogated the anti-apoptotic effect of MLIF in SH-SY5Y cells subjected to OGD, with an associated decrease in cell survival and an increase in expression of p-JNK and p53. These results indicate that MLIF ameliorates OGD-induced SH-SY5Y neuroblastoma injury by inhibiting the p-JNK/p53 apoptotic signaling pathway via eEF1A2. Our findings suggest that eEF1A2 may be a new therapeutic target for ischemic brain injury. PMID:26918757

  9. Fabrication of W-1%ThO[sub 2] reinforced Fe-25Cr-8Al-0. 5Y superalloy matrix composite

    SciTech Connect

    Armstrong, W.; Ramulu, M.; Taya, M. . Dept. of Mechanical Engineering)

    1994-01-01

    Four different aligned W-1%ThO[sub 2] reinforced Fe-25Cr-8Al-0.5Y matrix fiber reinforced superalloy [FRS] material billets were produced by powder metallurgical processing. Three materials differed only in reinforcing fiber aspect ratio, while one material included a small diameter, misoriented Al[sub 2]O[sub 3] hybrid reinforcement. Tensile and thermal cycling specimens were fabricated from the composite billets by using abrasive water jet and turning processes. Finally the specimens were protected from high temperature oxidation by a FeCrAlY thermal spray coating. Metallurgical and mechanical properties were evaluated and discussed.

  10. LX loaded nanoliposomes synthesis, characterization and cellular uptake studies in H2O2 stressed SH-SY5Y cells.

    PubMed

    Hasan, Murtaza; Iqbal, Javed; Awan, Umer; Xin, Nian; Dang, Hao; Waryani, Baradi; Saeed, Yasmeen; Ullah, Kaleem; Rongji, Dai; Deng, Yulin

    2014-06-01

    In this study, we report the cellular uptake studies of novel LX loaded nanoliposomes in H2O2 stress SH-SY5Y Cells synthesized by thin film evaporation method. We have isolated the smallest size nanoliposomes after 90 min ultrasonification, keeping Polydisperse Index as 0.259. The morphology, size, zepta potential and drug efficiency of prepared nanoliposomes are characterized by using Transmission Electron Microscope (TEM), particle size analyzer and High Pressure Liquid Chromatography (HPLC). The particle size analyzer have confirmed the particle size of nanoluposomes measured in range of 100-250 nm, whereas the shape of these nanoliposomes is almost spherical. The zeta potential of small size nanoliposomes was measured as -49.62 and encapsulation efficiency of the LX loaded nanoliposomes was 87%. The oxidative stress response in SH-SY5Y Cells for various doses of drug with and without nanoliposomes has affectively improved the cell-stress response up to 20% after 24 h of incubation at 37 degrees C. The results indicated that LX loaded nanoliposomes were taken by the cells effectively which ultimately improved the cell-stress response. Thus, this study confirmed that synthesized nanoliposomes are not only effective drug carriers but could be potentially used for delivery of genes, antibodies, and proteins in future. PMID:24738352

  11. Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells.

    PubMed

    Park, Jae Hyeon; Park, Youn Sun; Lee, Je-Bong; Park, Kyung-Hun; Paik, Min-kyoung; Jeong, Mihye; Koh, Hyun Chul

    2016-01-01

    Oxidative stress and inflammatory responses have been identified as key elements of neuronal cell apoptosis. In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in human neuroblastoma SH-SY5Y cells treated with fipronil (FPN). Based on the cytotoxic mechanism of FPN, we examined the neuroprotective effects of meloxicam against FPN-induced neuronal cell death. Treatment of SH-SY5Y cells with FPN induced apoptosis via activation of caspase-9 and -3, leading to nuclear condensation. In addition, FPN induced oxidative stress and increased expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) via inflammatory stimulation. Pretreatment of cells with meloxicam enhanced the viability of FPN-exposed cells through attenuation of oxidative stress and inflammatory response. FPN activated mitogen activated protein kinase (MAPK) and inhibitors of MAPK abolished FPN-induced COX-2 expression. Meloxicam also attenuated FPN-induced cell death by reducing MAPK-mediated pro-inflammatory factors. Furthermore, we observed both nuclear accumulation of p53 and enhanced levels of cytosolic p53 in a concentration-dependent manner after FPN treatment. Pretreatment of cells with meloxicam blocked the translocation of p53 from the cytosol to the nucleus. Together, these data suggest that meloxicam may exert anti-apoptotic effects against FPN-induced cytotoxicity by both attenuating oxidative stress and inhibiting the inflammatory cascade via inactivation of MAPK and p53 signaling. PMID:25772694

  12. PFOS Disturbs BDNF-ERK-CREB Signalling in Association with Increased MicroRNA-22 in SH-SY5Y Cells

    PubMed Central

    Li, Wu; He, Qing-zhi; Wu, Cheng-qiu; Pan, Xiao-yuan; Wang, Jing; Tan, Yan; Shan, Xiao-yun; Zeng, Huai-cai

    2015-01-01

    Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is neurotoxic to mammalian species. However, the underlying mechanism of its neurotoxicity was unclear. We hypothesized that PFOS suppresses BDNF expression to produce its neurotoxic effects by inhibiting the ERK-CREB pathway. SH-SY5Y human neuroblastoma cells were exposed to various concentrations of PFOS to examine the role of the BDNF-ERK-CREB signalling pathway in PFOS-induced apoptosis and cytotoxicity. Furthermore, to ascertain the mechanism by which PFOS reduces BDNF signalling, we examined the expression levels of miR-16 and miR-22, which potentially regulate BDNF mRNA translation at the posttranscriptional level. Results indicated that PFOS significantly decreased cell viability and induced apoptosis in SH-SY5Y cells. In addition, BDNF and pERK protein levels decreased after PFOS treatment; however, pCREB protein levels were significantly elevated in PFOS treated groups. TrkB protein expression increased in the 10 μM and 50 μM PFOS groups and significantly decreased in the 100 μM PFOS group. Our results demonstrated that PFOS exposure decreased miR-16 expression and increased miR-22 expression, which may represent a possible mechanism by which PFOS decreases BDNF protein levels. PFOS may inhibit BDNF-ERK-CREB signalling by increasing miR-22 levels, which may, in part, explain the mechanism of PFOS neurotoxicity. PMID:26649298

  13. Involvement of Mu Opioid Receptor Signaling in the Protective Effect of Opioid against 6-Hydroxydopamine-Induced SH-SY5Y Human Neuroblastoma Cells Apoptosis

    PubMed Central

    Eftekhar-Vaghefi, Shahrzad; Esmaeili-Mahani, Saeed; Elyasi, Leila; Abbasnejad, Mehdi

    2015-01-01

    Introduction: The neuroprotective role of opioid morphine against 6-hydroxydopamine-induced cell death has been demonstrated. However, the exact mechanism(s) underlying such neuroprotection, especially the role of subtype receptors, has not yet been fully clarified. Methods: Here, we investigated the effects of different opioid agonists on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson’s disease. Cell damage was induced by 150 μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species and mitochondrial membrane potential were assessed by fluorescence spectrophotometry method. Immunoblot technique was used to evaluate cytochrome-c and activated caspase-3 as biochemical markers of apoptosis induction. Results: The data showed that 6-OHDA caused significant cell damage, loss of mitochondrial membrane potential and increase in intracellular reactive oxygen species and calcium levels as well as activated caspase-3 and cytochrome-c release. Incubation of SH-SY5Y cells with μ-opioid agonists, morphine and DAMGO, but not with δ-opioid agonist, DADLE, elicited protective effect and reduced biochemical markers of cell damage and death. Discussion: The results suggest that μ-opioid receptors signaling participate in the opioid neuroprotective effects against 6-OHDA-induced neurotoxicity. PMID:26904174

  14. Transportation of Berberine into HepG2, HeLa and SY5Y Cells: A Correlation to Its Anti-Cancer Effect

    PubMed Central

    Pang, Yu-Nong; Liang, Yin-Wen; Feng, Tian-Shi; Zhao, Shuang; Wu, Hao; Chai, Yu-Shuang; Lei, Fan; Ding, Yi; Xing, Dong-Ming; Du, Li-Jun

    2014-01-01

    The anti-cancer activities of berberine (BBR) have been reported extensively in various cancer cell lines. However, the minimal inhibitory concentrations of BBR varied greatly among different cell lines and very few studies have been devoted to elucidate this aspect. In this study, we employed three cancer cell lines, HepG2, HeLa and SY5Y, to compare the transportation and distribution of BBR. HPLC results demonstrated that BBR was capable of penetrating all the cell lines whereas the cumulative concentrations were significantly different. HepG2 cells accumulated higher level of BBR for longer duration than the other two cell lines. Molecular docking studies revealed the BBR binding site on P-glycoprotein 1 (P-gp). In addition, we elucidated that BBR regulated P-gp at both mRNA and protein levels. BBR induced the transcription and translation of P-gp in HeLa and SY5Y cells, whereas BBR inhibited P-gp expression in HepG2 cells. Further study showed that BBR regulates P-gp expression depending on different mechanisms (or affected by different factors) in different cell lines. To summarize, our study has revealed several mechanistic aspects of BBR regulation on P-gp in different cancer cell lines and might shed some useful insights into the use of BBR in the anti-cancer drug development. PMID:25402492

  15. Chrysotoxine, a novel bibenzyl compound selectively antagonizes MPP⁺, but not rotenone, neurotoxicity in dopaminergic SH-SY5Y cells.

    PubMed

    Song, Ju-Xian; Shaw, Pang-Chui; Wong, Ngok-Shun; Sze, Cho-Wing; Yao, Xin-Sheng; Tang, Chi-Wai; Tong, Yao; Zhang, Yan-Bo

    2012-07-11

    Chrysotoxine is a naturally occurring bibenzyl compound found in medicinal Dendrobium species. We previously reported that chrysotoxine structure-specifically suppressed 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell death. Whether chrysotoxine and other structurally similar bibenzyl compounds could also inhibit the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP(+)) and rotenone has not been investigated. We showed herein that chrysotoxine inhibited MPP(+), but not rotenone, induced dopaminergic cell death in SH-SY5Y cells. The overproduction of reactive oxygen species (ROS), mitochondrial dysfunction as indexed by the decrease in membrane potential, increase in calcium concentration and NF-κB activation triggered by MPP(+) were blocked by chrysotoxine pretreatment. The imbalance between the pro-apoptotic signals (Bax, caspase-3, ERK and p38 MAPK) and the pro-survival signals (Akt/PI3K/GSK-3β) induced by MPP(+) was partially or totally rectified by chrysotoxine. The results indicated that ROS inhibition, mitochondria protection, NF-κB modulation and regulation of multiple signals determining cell survival and cell death were involved in the protective effects of chrysotoxine against MPP(+) toxicity in SH-SY5Y cells. Given the different toxic profiles of 6-OHDA and MPP(+) as compared to rotenone, our results also indicated that DAT inhibition may partially account for the neuroprotective effects of chrysotoxine. PMID:22659498

  16. Chrysotoxine, a novel bibenzyl compound, inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via mitochondria protection and NF-κB modulation.

    PubMed

    Song, Ju-Xian; Shaw, Pang-Chui; Sze, Cho-Wing; Tong, Yao; Yao, Xin-Sheng; Ng, Tzi-Bun; Zhang, Yan-Bo

    2010-11-01

    Some naturally occurring bibenzyl compounds have been reported as free radical scavengers. The present study tested our hypothesis that bibenzyl compounds may be neuroprotective against apoptosis induced by the neurotoxins. Five structurally similar bibenzyl derivatives were tested for their protective effect against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that one bibenzyl compound, namely chrysotoxine, significantly attenuated 6-OHDA-induced cell death. The subsequent mechanism study demonstrated that chrysotoxine significantly attenuated 6-OHDA-induced apoptosis characterized by DNA fragmentation and nuclear condensation in a dose-dependent manner. 6-OHDA-induced intracellular generation of reactive oxygen species (ROS), activation of p38 MAPK and ERK1/2, and mitochondrial dysfunctions, including the decrease of membrane potential, increase of intracellular free Ca2+, release of cytochrome c, imbalance of Bax/Bcl-2 ratio and activation of caspase-3 were strikingly attenuated by chrysotoxine pretreatment. Meanwhile, chrysotoxine counteracted NF-κB activation by blocking its translocation to the nucleus, thereby preventing up-regulation of inducible nitric oxide synthase (iNOS) and intracellular NO release. The data provide the first evidence that chrysotoxine protects SH-SY5Y cells against 6-OHDA toxicity possibly through mitochondria protection and NF-κB modulation. Chrysotoxine is thus a candidate for further evaluation of its protection against neurodegeneration in Parkinson's disease. PMID:20708055

  17. Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells

    PubMed Central

    Lee, Yang-ja; Miyake, Shin-ichi; Wakita, Hideaki; McMullen, David C; Azuma, Yoshiaki; Auh, Sungyoung; Hallenbeck, John M

    2008-01-01

    Hibernation torpor provides an excellent natural model of tolerance to profound reductions in blood flow to the brain and other organs. Here, we report that during torpor of 13-lined ground squirrels, massive SUMOylation occurs in the brain, liver, and kidney. The level of small ubiquitin-related modifier (SUMO) conjugation coincides with the expression level of Ubc9, the SUMO specific E2-conjugating enzyme. Hypothermia alone also increased SUMO conjugation, but not as markedly as hibernation torpor. Increased SUMO conjugation (induced by Ubc9 overexpression, ischemic preconditioning (PC)±hypothermia) was necessary and sufficient for tolerance of SHSY5Y neuroblastoma cells to oxygen/glucose deprivation (OGD) (‘in vitro ischemia’); decreased SUMO conjugation (induced by a dominant-negative Ubc9) severely reduced tolerance to OGD in these cells. These data indicate that post-translational modification of proteins by SUMOylation is a prominent feature of hibernation torpor and is critical for cytoprotection by ischemic PC± hypothermia in SHSY5Y cells subjected to OGD. PMID:16955077

  18. Quantitative proteomics study of the neuroprotective effects of B12 on hydrogen peroxide-induced apoptosis in SH-SY5Y cells

    PubMed Central

    Zhong, Lijun; Zhou, Juntuo; Chen, Xi; Lou, Yaxin; Liu, Dan; Zou, Xiajuan; Yang, Bin; Yin, Yuxin; Pan, Yan

    2016-01-01

    B12 belongs to the coumarin class of compounds that have been shown to have various physiological and pharmacological activities including anti-inflammatory, antibacterial, and antioxidant. In the present study, we characterised the neuroprotective effects of B12 against H2O2-induced neuronal cell damage in SH-SY5Y cells. Protein expression profiling in combination with pathway analysis was deployed to investigate the molecular events associated with the neuroprotective effects in human neuronal cells using a label-free quantitative proteomics approach. A total of 22 proteins were significantly differentially expressed in H2O2-damaged cells with or without B12 treatment. Bioinformatics analysis using the Cytoscape platform indicated that poly pyrimidine tract binding protein 1 (PTBP1) was highly associated with the protective effect, and western blotting verified that PTBP1 was up-regulated in H2O2 + B12 treatment group, compared with the H2O2 treated group. PTBP RNAi experiments knocked down PTBP expression, which cancelled out the protective effect of B12 on cell viability. Thus, we infer that B12 neuroprotective activity involves up-regulation of PTBP1 and its associated signalling networks following H2O2-induced apoptosis in SH-SY5Y cells. B12 or related compounds may prove to be useful therapeutic agents for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. PMID:26951766

  19. Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells: possible involvement of stress proteins and gene expression

    PubMed Central

    Nciri, Riadh; Bourogaa, Ezzeddine; Jbahi, Samira; Allagui, Mohamed Salah; Elfeki, Abdelfattah; Vincent, Christian; Croute, Françoise

    2014-01-01

    To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate (Li2CO2) for 25–50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2 (PKM2) and calmodulin 3 (CaM 3) expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II (CK2), threonine/tyrosine phosphatase 7 (PYST2), and dopamine beta-hydroxylase (DBH) expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins (HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modifications of proteins cited above. PMID:25206881

  20. Inhibition of myeloperoxidase-mediated oxidative damage by nitrite in SH-SY5Y cells: Relevance to neuroprotection in neurodegenerative diseases.

    PubMed

    Lu, Naihao; Ding, Yun; Tian, Rong; Peng, Yi-Yuan

    2016-06-01

    Myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) is elevated in many neurodegenerative diseases, and lead to severe tissue injuries. Nitrite (NO2(-)) is a widespread inorganic molecule that has recently been proposed as a direct NO donor to exert antioxidant properties in vivo and vitro. Since NO2(-) and MPO (and/or HOCl) were important mediators in brain function and disease, we investigated the effects of NO2(-) on MPO-mediated damage to human neuroblastoma SH-SY5Y cells. Here, we showed that exposure of SH-SY5Y cells to MPO (or HOCl) resulted in a significant loss in viability, ATP and glutathione levels, and treatment of neuronal cells with NO2(-) substantially attenuated MPO (or HOCl)-dependent cellular toxicity. The protective effects of NO2(-) on MPO (or HOCl)-induced cytotoxicity were because that (1) NO2(-) at high concentrations competed effectively with Cl(-) for MPO, thus limiting OCl(-) production by the enzyme; (2) HOCl was removed by reacting with NO2(-), forming less damaging compound; (3) NO2(-) significantly inhibited MPO-mediated inactivation of brain protein (enolase) and protein oxidation. Therefore, NO2(-) could show novel protective effects in some neurodegenerative diseases by preventing MPO-mediated oxidative damage. PMID:27020551

  1. L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway.

    PubMed

    Di, X; Yan, J; Zhao, Y; Zhang, J; Shi, Z; Chang, Y; Zhao, B

    2010-07-14

    As a natural analogue of glutamate, l-theanine is the unique amino acid derivative in green tea. Although its underlining mechanisms are not yet clear, it has been suggested that l-theanine treatment may prove beneficial to patients with neurodegenerative diseases. In this study, we investigated the neuroprotective effect and its mechanism of l-theanine in an in vitro model of Alzheimer's disease by using the human APP (Swedish mutation) transgenic SH-SY5Y cell. Amyloid beta (Abeta) neurotoxicity was triggered by l-glutamate in this cell line. Additionally, l-theanine significantly attenuated l-glutamate-induced apoptosis at similar levels to those seen with the NMDA receptor inhibitor MK-801 in the stably expressing APP Swedish mutation SH-SY5Y cells which over-generated Abeta. Meanwhile, the activation of c-Jun N-terminal kinase and caspase-3 induced by l-glutamate was suppressed by l-theanine. We also found that cells treated with l-theanine showed decreased production of nitric oxide resulting from the down-regulated protein levels of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). These results indicate that the inhibition of the NMDA subtype of glutamate receptors and its related pathways is the crucial point of the neuroprotective effect of l-theanine in the cell model. Thus, our present study supports the notion that l-theanine may provide effective prophylaxis and treatment for Alzheimer's disease. PMID:20416364

  2. Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal.

    PubMed

    Waly, Mostafa; Power-Charnitsky, Verna-Ann; Hodgson, Nathaniel; Sharma, Alok; Audhya, Tapan; Zhang, Yiting; Deth, Richard

    2016-01-01

    The folate and cobalamin (Cbl-) dependent enzyme methionine synthase (MS) is highly sensitive to oxidation and its activity affects all methylation reactions. Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts. Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes. MS activity was dependent upon methylcobalamin (MeCbl) or the combination of hydroxocobalamin (OHCbl) and S-adenosylmethionine (SAM). OHCbl-based activity was eliminated by depletion of the antioxidant glutathione (GSH) but could be rescued by provision of either glutathionylcobalamin (GSCbl) or MeCbl. Pretreatment of cells with lead, arsenic, aluminum, mercury, or the ethylmercury-containing preservative thimerosal lowered GSH levels and inhibited MS activity in association with decreased uptake of cysteine, which is rate-limiting for GSH synthesis. Thimerosal treatment decreased cellular levels of GSCbl and MeCbl. These findings indicate that the alternatively spliced form of MS expressed in SH-SY5Y human neuronal cells is sensitive to inhibition by thimerosal and neurotoxic metals, and lower GSH levels contribute to their inhibitory action. PMID:26989453

  3. Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells: possible involvement of stress proteins and gene expression.

    PubMed

    Nciri, Riadh; Bourogaa, Ezzeddine; Jbahi, Samira; Allagui, Mohamed Salah; Elfeki, Abdelfattah; Vincent, Christian; Croute, Françoise

    2014-04-01

    To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate (Li2CO2) for 25-50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2 (PKM2) and calmodulin 3 (CaM 3) expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II (CK2), threonine/tyrosine phosphatase 7 (PYST2), and dopamine beta-hydroxylase (DBH) expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins (HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modifications of proteins cited above. PMID:25206881

  4. Biochemical Characterization of Liver Oil of Echinorhinus brucus (Bramble Shark) and Its Cytotoxic Evaluation on Neuroblastoma Cell Lines (SHSY-5Y)

    PubMed Central

    Venugopal, Vishnu; Kumaran, Ajeeshkumar Kizhakkepurath; Sekhar Chatterjee, Niladri; Kumar, Suvanish; Kavilakath, Shyni; Nair, Jayarani Ramachandran; Mathew, Suseela

    2016-01-01

    The objective of the present study was to characterize the liver oil extracted from the deep sea shark, Echinorhinus brucus, caught from Central Indian Ocean and to evaluate its cytotoxic effect on neuroblastoma cell line (SHSY-5Y). Characterization of liver oil of Echinorhinus brucus revealed the presence of palmitic acid (15%), oleic acid (12%), stearic acid (8%), docosahexaenoic acid (DHA) (18%), and eicosapentaenoic acid (EPA) (16%). It was also found to be a good source of squalene (38.5%) and fat soluble vitamins such as A, D, and K (vitamin A: 17.08 mg/100 g of oil, vitamin D: 15.04 mg/100 g oil, and vitamin K: 11.45 mg/100 g oil). Since it was found to be rich in essential fatty acids, fat soluble vitamins, and squalene, it can be considered as better dietary supplement. The oil of Echinorhinus brucus also showed high in vitro cytotoxic effect against the human neuroblastoma cell line (SHSY-5Y) and the IC50 value laid between 35 and 45 ng. PMID:27340593

  5. Preparation and electrochemical magnesium insertion behaviors of Mg 0.5+ y(Me yTi 1- y) 2(PO 4) 3 (Me = Cr, Fe)

    NASA Astrophysics Data System (ADS)

    Makino, Koji; Katayama, Yasushi; Miura, Takashi; Kishi, Tomiya

    A series of transition metal phosphates, Mg 0.5+ y(Fe yTi 1- y) 2(PO 4) 3 (MFTP) and Mg 0.5+ y(Cr yTi 1- y) 2(PO 4) 3 (MCTP), modified from Mg 0.5Ti 2(PO 4) 3 (MTP) were prepared by sol-gel method and evaluated as a possible cathode material for magnesium cells. The lattice structures of MFTP and MCTP at 0≤ y≤0.5 were identical with that of MTP, while their unit cell volumes were smaller than that of MTP due to the increased amount of Mg 2+ ions. Electrochemical magnesium insertion into MFTP and MCTP was found to be possible as observed for MTP. However, the limiting extent of magnesium insertion into MFTP at 0.1≤ y≤0.5 was small compared with MTP and remarkably dependent on the discharge current density during discharge. These facts suggested that the insertion limit is determined not by the number of available sites for Mg 2+ or electrons but by the mobility of Mg 2+ in these host materials correlating with decrease in the unit cell volume.

  6. Biochemical Characterization of Liver Oil of Echinorhinus brucus (Bramble Shark) and Its Cytotoxic Evaluation on Neuroblastoma Cell Lines (SHSY-5Y).

    PubMed

    Venugopal, Vishnu; Kumaran, Ajeeshkumar Kizhakkepurath; Sekhar Chatterjee, Niladri; Kumar, Suvanish; Kavilakath, Shyni; Nair, Jayarani Ramachandran; Mathew, Suseela

    2016-01-01

    The objective of the present study was to characterize the liver oil extracted from the deep sea shark, Echinorhinus brucus, caught from Central Indian Ocean and to evaluate its cytotoxic effect on neuroblastoma cell line (SHSY-5Y). Characterization of liver oil of Echinorhinus brucus revealed the presence of palmitic acid (15%), oleic acid (12%), stearic acid (8%), docosahexaenoic acid (DHA) (18%), and eicosapentaenoic acid (EPA) (16%). It was also found to be a good source of squalene (38.5%) and fat soluble vitamins such as A, D, and K (vitamin A: 17.08 mg/100 g of oil, vitamin D: 15.04 mg/100 g oil, and vitamin K: 11.45 mg/100 g oil). Since it was found to be rich in essential fatty acids, fat soluble vitamins, and squalene, it can be considered as better dietary supplement. The oil of Echinorhinus brucus also showed high in vitro cytotoxic effect against the human neuroblastoma cell line (SHSY-5Y) and the IC50 value laid between 35 and 45 ng. PMID:27340593

  7. Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation.

    PubMed

    Lee, Joomin; Ahn, Eunsook; Park, Wyun Kon; Park, Seyeon

    2016-01-01

    Inhalation anesthetics are used to decrease the spinal cord transmission of painful stimuli. However, the molecular or biochemical processes within cells that regulate anesthetic-induced responses at the cellular level are largely unknown. Here, we report the phosphoproteome profile of SH-SY5y human neuroblastoma cells treated with sevoflurane, a clinically used anesthetic. Phosphoproteins were isolated from cell lysates and analyzed using two-dimensional gel electrophoresis. The phosphorylation of putative anesthetic-responsive marker proteins was validated using western blot analysis in cells treated with both sevoflurane and isoflurane. A total of 25 phosphoproteins were identified as differentially phosphorylated proteins. These included key regulators that signal cytoskeletal remodeling steps in pathways related to vesicle trafficking, axonal growth, and cell migration. These proteins included the Rho GTPase, Ras-GAP SH3 binding protein, Rho GTPase activating protein, actin-related protein, and actin. Sevoflurane and isoflurane also resulted in the dissolution of F-actin fibers in SH-SY5y cells. Our results show that anesthetics affect the phosphorylation of proteins involved in cytoskeletal remodeling pathways. PMID:27611435

  8. Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal

    PubMed Central

    Power-Charnitsky, Verna-Ann; Sharma, Alok; Audhya, Tapan; Zhang, Yiting

    2016-01-01

    The folate and cobalamin (Cbl-) dependent enzyme methionine synthase (MS) is highly sensitive to oxidation and its activity affects all methylation reactions. Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts. Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes. MS activity was dependent upon methylcobalamin (MeCbl) or the combination of hydroxocobalamin (OHCbl) and S-adenosylmethionine (SAM). OHCbl-based activity was eliminated by depletion of the antioxidant glutathione (GSH) but could be rescued by provision of either glutathionylcobalamin (GSCbl) or MeCbl. Pretreatment of cells with lead, arsenic, aluminum, mercury, or the ethylmercury-containing preservative thimerosal lowered GSH levels and inhibited MS activity in association with decreased uptake of cysteine, which is rate-limiting for GSH synthesis. Thimerosal treatment decreased cellular levels of GSCbl and MeCbl. These findings indicate that the alternatively spliced form of MS expressed in SH-SY5Y human neuronal cells is sensitive to inhibition by thimerosal and neurotoxic metals, and lower GSH levels contribute to their inhibitory action. PMID:26989453

  9. Carnosic Acid Prevents Beta-Amyloid-Induced Injury in Human Neuroblastoma SH-SY5Y Cells via the Induction of Autophagy.

    PubMed

    Liu, Jie; Su, Hua; Qu, Qiu-Min

    2016-09-01

    Beta-amyloid (Aβ), the hallmark protein in Alzheimer's disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a polyphenolic diterpene isolated from the herb rosemary (Rosemarinus officinalis), was investigated in our study to assess its neuroprotective effect and underlying mechanism against Aβ-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the Aβ25-35-induced loss of cell viability, inhibited both Aβ1-42 accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPKα successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD. PMID:27168327

  10. Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y cells.

    PubMed

    Zeng, H; Huang, P; Wang, X; Wu, J; Wu, M; Huang, J

    2015-05-21

    Alzheimer's disease (AD), the most common cause of dementia in aging people, is found to have a critical link with the deposition of β-amyloid (Aβ) in the brain. The inhibition of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), a key enzyme for Aβ production, is a promising target for AD therapy. In pursuit to find a potent inhibitor of BACE1, we identified galangin, a natural flavonoid, had a significant lowering effect on Aβ levels. Furthermore, a dramatic reduction of BACE1 at mRNA and protein levels was observed after galangin treatment. We further investigated whether epigenetic mechanisms, such as histone acetylation and DNA methylation, were involved in galangin-induced transcriptional regulation of BACE1. Our data show that galangin induces a decrease of acetylated H3 in the BACE1 promoter regions through the up-regulation of endogenous HDAC1-mediated deacetylation, which is independent of DNA methylation status. The above findings suggest a novel mechanism for polyphenols' neuroprotective effect in neurodegeneration and galangin as a potential drug candidate for AD therapy. PMID:25779965

  11. Aging Brain, Aging Mind.

    ERIC Educational Resources Information Center

    Selkoe, Dennis J.

    1992-01-01

    Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

  12. Terrestrial Ages of Antarctic Meteorites- Update 1999

    NASA Technical Reports Server (NTRS)

    Nishiizumi, Kunihiko; Welten, K. C.; Caffee, Marc W.

    1999-01-01

    We are continuing our ongoing study of cosmogenic nuclides in Antarctic meteorites. In addition to the studies of exposure histories of meteorites, we study terrestrial ages and pairing of Antarctic meteorites and desert meteorites. Terrestrial ages of Antarctic meteorites provide information on meteorite accumulation mechanisms, mean weathering lifetimes, and influx rates. The determination of Cl-36(half-life=3.01 x 10(exp 5) y) terrestrial ages is one of our long-term on-going projects, however, in many instances neither Cl-36 or C-14 (5,730 y) yields an accurate terrestrial age. Using Ca-14 (1.04 x 10(exp 5) y) for terrestrial age determinations solves this problem by filling the c,ap in half-life between 14-C and Cl-36 ages. We are now applying the new Ca-41- Cl-36 terrestrial age method as well as the Cl-36-Be-10 method to Antarctic meteorites. Our measurements and C-14 terrestrial age determinations by the University of Arizona group are always complementary. We have measured Cl-36 in over 270 Antarctic meteorites since our previous compilation of terrestrial ages. Since a large number of meteorites have been recovered from many different icefields in Antarctica, we continue to survey the trends of terrestrial ages for different icefields. We have also measured detailed terrestrial ages vs. sample locations for Allan Hills, Elephant Moraine, and Lewis Cliff Icefields, where meteorites have been found with very long ages. The updated histograms of terrestrial ages of meteorites from the Allan Hills Main Icefield and Lewis Cliff Icefield are shown. These figures include C-14 ages obtained by the University of Arizona group. Pairs of meteorites are shown as one object for which the age is the average of all members of the same fall. The width of the bars represents 70,000 years, which was a typical uncertainty for Cl-36 ages. We reduced the uncertainty of terrestrial age determinations to approx. 40,000 years by using pairs of nuclides such as Ca-41-Cl-36 or Cl

  13. Lysophosphatidic acid-mediated Ca2+ mobilization in human SH-SY5Y neuroblastoma cells is independent of phosphoinositide signalling, but dependent on sphingosine kinase activation.

    PubMed

    Young, K W; Challiss, R A; Nahorski, S R; MacKrill, J J

    1999-10-01

    Extracellular application of lysophosphatidic acid (LPA) elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) in human SH-SY5Y neuroblastoma cells. The maximal response to LPA occurred between 0. 1 and 1 microM, at which point [Ca(2+)](i) was increased by approx. 500 nM. This increase was of similar magnitude to that caused by the muscarinic acetylcholine receptor agonist methacholine (MCh), although the initial rate of release by LPA was slower. Both LPA and MCh released Ca(2+) from intracellular stores, as assessed by inhibition of their effects by thapsigargin, a blocker of endoplasmic reticular Ca(2+) uptake, and by the persistence of their action in nominally Ca(2+)-free extracellular medium. Similarly, both agonists appeared to stimulate store-refilling Ca(2+) entry. MCh produced a marked elevation in cellular Ins(1,4,5)P(3) and stimulated [(3)H]InsP accumulation in the presence of Li(+). In contrast, LPA failed to stimulate detectable phosphoinositide turnover. Chronic down-regulation of Ins(1,4,5)P(3) receptor (InsP(3)R) proteins with MCh did not affect Ca(2+) responses to LPA. In addition, heparin, a competitive antagonist of InsP(3)Rs, blocked Ca(2+)-mobilization in permeabilized SH-SY5Y cells in response to MCh or exogenously added Ins(1,4,5)P(3), but failed to inhibit Ca(2+)-release induced by LPA. Elevation of [Ca(2+)](i) elicited by LPA was blocked by guanosine 5'-[beta-thio]-diphosphate, indicating that this agonist acts via a G-protein-coupled receptor. However, pertussis toxin was without effect on LPA-evoked [Ca(2+)](i) responses, suggesting that G(i/o)-proteins were not involved. In the absence of extracellular Ca(2+), N,N-dimethylsphingosine (DMS, 30 microM), a competitive inhibitor of sphingosine kinase, blocked LPA-induced Ca(2+) responses by almost 90%. In addition, MCh-induced Ca(2+) responses were also diminished by the addition of DMS, although to a lesser extent than with LPA. We conclude that LPA mobilizes intracellular Ca(2

  14. Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells.

    PubMed

    Uğuz, Abdülhadi Cihangir; Öz, Ahmi; Nazıroğlu, Mustafa

    2016-08-01

    Neurological diseases such as Alzheimer's and Parkinson's diseases are incurable progressive neurological disorders caused by the degeneration of neuronal cells and characterized by motor and non-motor symptoms. Curcumin, a turmeric product, is an anti-inflammatory agent and an effective reactive oxygen and nitrogen species scavenging molecule. Hydrogen peroxide (H2O2) is the main source of oxidative stress, which is claimed to be the major source of neurological disorders. Hence, in this study we aimed to investigate the effect of curcumin on Ca(2+) signaling, oxidative stress parameters, mitochondrial depolarization levels and caspase-3 and -9 activities that are induced by the H2O2 model of oxidative stress in SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were divided into four groups namely, the control, curcumin, H2O2, and curcumin + H2O2 groups. The dose and duration of curcumin and H2O2 were determined from published data. The cells in the curcumin, H2O2, and curcumin + H2O2 groups were incubated for 24 h with 5 µM curcumin and 100 µM H2O2. Lipid peroxidation and cytosolic free Ca(2+) concentrations were higher in the H2O2 group than in the control group; however, their levels were lower in the curcumin and curcumin + H2O2 groups than in the H2O2 group alone. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values were lower in the H2O2 group although they were higher in the curcumin and curcumin + H2O2 groups than in the H2O2 group. Caspase-3 activity was lower in the curcumin group than in the H2O2 group. In conclusion, curcumin strongly induced modulator effects on oxidative stress, intracellular Ca(2+) levels, and the caspase-3 and -9 values in an experimental oxidative stress model in SH-SY5Y cells. PMID:26608462

  15. Transglutaminase-2 Is Involved in All-Trans Retinoic Acid-Induced Invasion and Matrix Metalloproteinases Expression of SH-SY5Y Neuroblastoma Cells via NF-κB Pathway

    PubMed Central

    Lee, Hye Ja; Park, Mi Kyung; Bae, Hyun Cheol; Yoon, Hee Jung; Kim, Soo Youl; Lee, Chang Hoon

    2012-01-01

    All-trans retinoic acid (ATRA) is currently used in adjuvant differentiation-based treatment of residual or relapsed neuroblastoma (NB). It has been reported that short-term ATRA treatment induces migration and invasion of SH-SY5Y via transglutaminase-2 (Tgase-2). However, the detailed mechanism of Tgase-2's involvement in NB cell invasion remains unclear. Therefore we investigated the role of Tgase-2 in invasion of NB cells using SH-SY5Y cells. ATRA dose-dependently induced the invasion of SH-SY5Y cells. Cystamine (CTM), a well known tgase inhibitor suppressed the ATRA-induced invasion of SH-SY5Y cells in a dose-dependent manner. Matrix metalloproteinase-9 (MMP-9) and MMP-2, well known genes involved in invasion of cancer cells were induced in the ATRA-induced invasion of the SH-SH5Y cells. Treatment of CTM suppressed the MMP-9 and MMP-2 enzyme activities in the ATRA-induced invasion of the SH-SY5Y cells. To confirm the involvement of Tgase-2, gene silencing of Tgase-2 was performed in the ATRA-induced invasion of the SH-SH5Y cells. The siRNA of Tgase-2 suppressed the MMP-9 and MMP-2 activity of the SH-SY5Y cells. MMP-2 and MMP-9 are well known target genes of NF-κB. Therefore the relationship of Tgase-2 and NF-κB in the ATRA-induced invasion of the SH-SY5Y cells was examined using siRNA and CTM. ATRA induced the activation of NF-κB in the SH-SY5Y cells and CTM suppressed the activation of NF-κB. Gene silencing of Tgase-2 suppressed the MMP expression by ATRA. These results suggested that Tgase-2 might be a new target for controlling the ATRA-induced invasion of NBs. PMID:24130925

  16. PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes.

    PubMed

    Ferguson, Ross; Subramanian, Vasanta

    2016-01-01

    Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease. PMID:27391595

  17. Neuropeptide FF-sensitive confinement of mu opioid receptor does not involve lipid rafts in SH-SY5Y cells

    SciTech Connect

    Mouledous, Lionel

    2008-08-15

    *: Mu opioid (MOP) receptor activation can be functionally modulated by stimulation of Neuropeptide FF 2 (NPFF{sub 2}) G protein-coupled receptors. Fluorescence recovery after photobleaching experiments have shown that activation of the NPFF{sub 2} receptor dramatically reduces the fraction of MOP receptors confined in microdomains of the plasma membrane of SH-SY5Y neuroblastoma cells. The aim of the present work was to assess if the direct observation of receptor compartmentation by fluorescence techniques in living cells could be related to indirect estimation of receptor partitioning in lipid rafts after biochemical fractionation of the cell. Our results show that MOP receptor distribution in lipid rafts is highly dependent upon the method of purification, questioning the interpretation of previous data regarding MOP receptor compartmentation. Moreover, the NPFF analogue 1DMe does not modify the distribution profile of MOP receptors, clearly demonstrating that membrane fractionation data do not correlate with direct measurement of receptor compartmentation in living cells.

  18. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest.

    PubMed

    Zargan, Jamil; Sajad, Mir; Umar, Sadiq; Naime, Mohammad; Ali, Shakir; Khan, Haider A

    2011-08-01

    The purpose of study was to examine the cytotoxic and anti-cancer properties along with addressing the plausible pathway followed by scorpion venom to reduce cell viability in SH-SY5Y and MCF-7 cells. Following exposure of cells with scorpion venom, cytotoxicity was estimated using MTT and lactate dehydrogenase assays. Apoptotic effects were measured by assessment of mitochondrial membrane potential, reactive nitrogen species, DNA fragmentation, and caspase-3 activity whereas antiproliferative effect was assayed using BrdU incorporation. Our results indicate that scorpion venom causes suppression of proliferation by arresting S-phase and induction of apoptosis through increased nitric oxide production, caspase-3 activity and depolarization of mitochondrial membrane. Induction of apoptosis and arrest of DNA synthesis are critical determinant factors for development of anti cancer drugs. These properties may lead to isolation of effective molecule(s) with potential anticancer activity from scorpion venom of Androctonus crassicauda. PMID:21536027

  19. Opioid receptors in human neuroblastoma SH-SY5Y cells: evidence for distinct morphine (. mu. ) and enkephalin (delta) binding sites

    SciTech Connect

    Kazmi, S.M.I.; Mishra, R.K.

    1986-06-13

    Human neuroblastoma SH-SY5Y cells exhibited a heterogeneous population of ..mu.. and delta types of opioid binding sites. These specific binding sites displayed the characteristic saturability, stereospecificity and reversibility, expected of a receptor. Scatchard analysis of (/sup 3/H)-D-Ala/sup 2/-D-Leu/sup 5/-enkephalin (DADLE) in the presence of 10/sup -5/M D-Pro/sup 4/-morphiceptin (to block the ..mu.. receptors) and the competitive displacement by various highly selective ligands yielded the binding parameters of delta sites which closely resemble those of the delta receptors in brain and mouse neuroblastoma clones. Similarly, the high affinity binding of (/sup 3/H)-dihydromorphine, together with the higher potency of morphine analogues to displace (/sup 3/H)-naloxone binding established the presence of ..mu.. sites. Guanine nucleotides and NaCl significantly inhibited the association and increased the dissociation of (/sup 3/H)-DADLE binding.

  20. PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes

    PubMed Central

    Ferguson, Ross; Subramanian, Vasanta

    2016-01-01

    Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease. PMID:27391595

  1. Low temperature co-sintering of Sr2Fe1.5Mo0.5O6-δ-Gd0.1Ce0.9O2-δ anode-supported solid oxide fuel cells with Li2O-Gd0.1Ce0.9O2-δ electrolyte

    NASA Astrophysics Data System (ADS)

    Yang, Zhibin; Yang, Yanru; Chen, Yu; Liu, Yahui; Zhu, Tenglong; Han, Minfang; Chen, Fanglin

    2015-11-01

    Sr2Fe1.5Mo0.5O6-δ-Gd0.1Ce0.9O1.95(SFM-GDC) ceramic anode-supported solid oxide fuel cell with GDC crack-free electrolyte film (∼80 μm) has been fabricated by co-pressing and co-sintering at temperature as low as 1150 °C for 5 h by introducing 2.5 mol% Li2O as sintering-aid. The peak power density of such cells with Ba0.9Co0.7Fe0.2Nb0.1O3-δ (BCFN) cathode can reach 200 mW cm-2 at 700 °C when using H2 as fuel and ambient air as oxidant. In addition, the anode shows an excellent sulfur tolerance when using H2 with 50 ppm H2S as fuel.

  2. Organic solvent-induced changes in membrane geometry in human SH-SY5Y neuroblastoma cells - a common narcotic effect?

    PubMed

    Meulenberg, Cécil J W; de Groot, Aart; Westerink, Remco H S; Vijverberg, Henk P M

    2016-07-01

    Exposure to organic solvents may cause narcotic effects. At the cellular level, these narcotic effects have been associated with a reduction in neuronal excitability caused by changes in membrane structure and function. In order to critically test whether changes in membrane geometry contribute to these narcotic effects, cultured human SH-SY5Y neuroblastoma cells have been exposed to selected organic solvents. The solvent-induced changes in cell membrane capacitance were investigated using the whole-cell patch clamp technique for real-time capacitance measurements. Exposure of SH-SY5Y cells to the cyclic hydrocarbons m-xylene, toluene, and cyclohexane caused a rapid and reversible increase of membrane capacitance. The aliphatic, nonpolar n-hexane did not cause a detectable change of whole-cell membrane capacitance, whereas the amphiphiles n-hexanol and n-hexylamine caused an increase of membrane capacitance and a concomitant reduction in membrane resistance. Despite a large difference in dielectric properties, the chlorinated hydrocarbons 1,1,2,2-tetrachoroethane and tetrachloroethylene caused a similar magnitude increase in membrane capacitance. The theory on membrane capacitance has been applied to deduce changes in membrane geometry caused by solvent partitioning. Although classical observations have shown that solvents increase the membrane capacitance per unit area of membrane, i.e., increase membrane thickness, the present results demonstrate that solvent partitioning predominantly leads to an increase in membrane surface area and to a lesser degree to an increase in membrane thickness. Moreover, the present results indicate that the physicochemical properties of each solvent are important determinants for its specific effects on membrane geometry. This implies that the hypothesis that solvent partitioning is associated with a common perturbation of membrane structure needs to be revisited and cannot account for the commonly observed narcotic effects of

  3. Extremely Low Frequency Magnetic Field (ELF-MF) Exposure Sensitizes SH-SY5Y Cells to the Pro-Parkinson's Disease Toxin MPP(.).

    PubMed

    Benassi, Barbara; Filomeni, Giuseppe; Montagna, Costanza; Merla, Caterina; Lopresto, Vanni; Pinto, Rosanna; Marino, Carmela; Consales, Claudia

    2016-08-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, with an etiopathogenesis involving both genetic and environmental factors. The occupational/residential exposure to the electromagnetic fields has been recently associated with an increased risk of neurodegenerative diseases; it has been thus proposed that the extremely low frequency magnetic field (ELF-MF) may contribute to neurodegenerative etiopathogenesis, as its interaction with biological systems directly impairs redox homeostasis in specific areas of the brain. The molecular mechanisms elicited by ELF-MF, and their potential involvement in PD onset, still remain unclear. To this end, we set up a generator of ELF-MF able to stably and homogeneously reproduce environmental prolonged exposure to ELF-MF (50 Hz, 1 mT). Results obtained indicate that ELF-MF exposure alters cell response of SH-SY5Y cells to MPP(+). We demonstrate that ELF-MF does not affect per se survival, shape, and morphology of both proliferating and differentiated SH-SY5Y cells but significantly impairs redox homeostasis and thiol content, triggering an increase in protein carbonylation. As a result, toxicity of MPP(+), even at low doses, is highly enhanced in ELF-MF-exposed cells due to a significant increase in ROS levels, potentiation of oxidative damage, and induction of a caspase-dependent apoptosis. Pre-incubation with the thiol antioxidants N-acetyl-L-cysteine and GSH ethyl-ester significantly reduces the extent of oxidative damage and protects cells from death induced by the combined treatment ELF-MF/MPP(+). Taken overall, our results demonstrate the redox-based molecular interaction between ELF-MF and PD neurotoxins in vitro, and open a new scenario for defining the synergy of environmental factors in PD onset. PMID:26223801

  4. Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-α2.

    PubMed

    Valeria, Righi; Luisa, Schenetti; Adele, Mucci; Stefania, Benatti; Fabio, Tascedda; Nicoletta, Brunello; Carmine, Pariante M; Silvia, Alboni

    2016-03-01

    Interferon (IFN)-α2 is an extensively therapeutically used pro-inflammatory cytokine. Though its efficacy in controlling viral replication and tumor cells proliferation, administration of IFN-α2 is often associated with the development of central side effects. Magnetic resonance spectroscopy studies have demonstrated that IFN-α2 administration affects brain metabolism, however the exact nature of this effect is not completely known. We hypothesized that IFN-α2 can affect metabolic activity of human neuron-like SH-SY5Y cells which possess many characteristics of neurons and represent one of the most used models for studying mechanisms involved in neurotoxicity or neuroprotection. To test our hypothesis we have characterized the metabolic signature of live SH-SY5Y, and their conditioned media, after 24 and 72 h of exposure to vehicle or IFN-α2 (100 ng/ml) by using High Resolution-Magic Angle Spinning (HR-MAS) Nuclear Magnetic Resonance (NMR) spectroscopy. Our results revealed that 1) the use of HR-MAS NMR is ideally suitable for the characterization of the metabolic profile of live cells and their conditioned media without extraction procedures; and 2) a 72 h exposure to IFN-α2 increases the level of metabolites involved in maintaining energetic (including creatine and lactate) and osmotic (such as myo-inositol, scyllo-inositol, taurine and glycerophosphorylcholine) balances in neuron-like cells and of metabolic waste products (namely lactate, ethanol and acetate), glycine and glutamine in their growth media. These results may contribute to gain more knowledge about the IFN-α2 induced effect on the brain and support the interpretation of magnetic resonance spectroscopy studies performed in humans. PMID:26541470

  5. L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations.

    PubMed

    Okle, Oliver; Stemmer, Kerstin; Deschl, Ulrich; Dietrich, Daniel R

    2013-01-01

    The cyanobacterial β-N-methylamino-L-alanine (L-BMAA) is described as a low-potency excitotoxin, possibly a factor in the increased incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) in Guam. The latter association is intensively disputed, as L-BMAA concentrations required for toxic effects exceed those assumed to occur via food. The question thus was raised whether L-BMAA leads to neurodegeneration at nonexcitotoxic conditions. Using human SH-SY5Y neuroblastoma cells, L-BMAA-transport, incorporation into proteins, and subsequent impairment of cellular protein homeostasis were investigated. Binding of L-BMAA to intracellular proteins, but no clear protein incorporation was detected in response to (14)C-L-BMAA exposures. Nevertheless, low L-BMAA concentrations (≥ 0.1mM, 48 h) increased protein ubiquitination, 20S proteasomal and caspase 12 activity, expression of the endoplasmic reticulum (ER) stress marker CHOP, and enhanced phosphorylation of elf2α in SH-SY5Y cells. In contrast, high L-BMAA concentrations (≥ 1mM, 48 h) increased reactive oxygen species and protein oxidization, which were partially ameliorated by coincubation with vitamin E. L-BMAA-mediated cytotoxicity was observable 48 h following ≥ 2mM L-BMAA treatment. Consequently, the data presented here suggest that low L-BMAA concentrations result in a dysregulation of the cellular protein homeostasis with ensuing ER stress that is independent from high-concentration effects such as excitotoxicity and oxidative stress. Thus, the latter could be a contributing factor in the onset and slow progression of ALS/PDC in Guam. PMID:23047912

  6. Rosiglitazone inhibits chlorpyrifos-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells

    SciTech Connect

    Lee, Jeong Eun; Park, Jae Hyeon; Jang, Sea Jeong; Koh, Hyun Chul

    2014-07-15

    Oxidative stress can lead to expression of inflammatory transcription factors, which are important regulatory elements in the induction of inflammatory responses. One of the transcription factors, nuclear transcription factor kappa-B (NF-κB) plays a significant role in the inflammation regulatory process. Inflammatory cell death has been implicated in neuronal cell death in some neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying apoptosis initiated by chlorpyrifos (CPF)-mediated oxidative stress. Based on the cytotoxic mechanism of CPF, we examined the neuroprotective effects of rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, against CPF-induced neuronal cell death. The treatment of SH-SY5Y cells with CPF induced oxidative stress. In addition, CPF activated the p38, JNK and ERK mitogen-activated protein kinases (MAPKs), and induced increases in the inflammatory genes such as COX-2 and TNF-α. CPF also induced nuclear translocation of NF-κB and inhibitors of NF-κB abolished the CPF-induced COX-2 expression. Pretreatment with RGZ significantly reduced ROS generation and enhanced HO-1 expression in CPF-exposed cells. RGZ blocked the activation of both p38 and JNK signaling, while ERK activation was strengthened. RGZ also attenuated CPF-induced cell death through the reduction of NF-κB-mediated proinflammatory factors. Results from this study suggest that RGZ may exert an anti-apoptotic effect against CPF-induced cytotoxicity by attenuation of oxidative stress as well as inhibition of the inflammatory cascade via inactivation of signaling by p38 and JNK, and NF-κB. - Highlights: • CPF induces apoptotic cell death in SH-SY5Y cells • ROS involved in CPF-mediated apoptotic cell death • Inflammation involved in CPF-mediated apoptotic cell death • Rosiglitazone modulates ROS and inflammatory response in CPF-treated cells.

  7. Inhibition of N-type Ca2+ channel currents in human neuroblastoma (SH-SY5Y) cells by muscarine via stimulation of M3 receptors.

    PubMed

    Reeve, H L; Vaughan, P F; Peers, C

    1995-03-01

    The effects of muscarine on whole-cell Ca2+ channel currents in SH-SY5Y cells were studied using conventional and perforated-patch-clamp techniques, with 10 mM Ba2+ as charge carrier. Muscarine (10-300 microM) caused concentration-dependent inhibitions of Ca2+ channel currents which were only reversible when perforated-patch recordings were used. Inhibition of currents was associated with slowing of activation kinetics in approximately 50% of cells. In the presence of 5 microM nifedipine, muscarine was still able to inhibit currents, but after pre-exposure of cells to 1 microM omega-conotoxin GVIA the inhibitory effects of muscarine were almost completely lost. In the presence of 100 microM muscarine, Bay K 8644 (5 microM) was still able to enhance current amplitudes. Pre-treatment of cells with pertussis toxin (250 ng/ml for 16-24 hr) or inclusion of 1 mM GDP-beta-S in the patch-pipette prevented the inhibitory actions of muscarine. Hexahydrosiladifenidol (0.1-1 microM) antagonized the actions of muscarine (calculated pA2 7.1) but the presence of 10 microM pirenzipine or 0.1 microM methoctramine in the bath solution did not alter the degree of current inhibition caused by 100 microM muscarine. In summary, these results indicate that muscarine in SH-SY5Y cells causes inhibition of N-type Ca2+ channels via a M3 receptor coupled to a pertussis toxin-sensitive G-protein. PMID:7630487

  8. Retinoic acid-induced differentiation of human neuroblastoma SH-SY5Y cells is associated with changes in the abundance of G proteins.

    PubMed

    Ammer, H; Schulz, R

    1994-04-01

    Western blot analysis, using subtype-specific anti-G protein antibodies, revealed the presence of the following G protein subunits in human neuroblastoma SH-SY5Y cells: Gs alpha, Gi alpha 1, Gi alpha 2, Go alpha, Gz alpha, and G beta. Differentiation of the cells by all-trans-retinoic acid (RA) treatment (10 mumol/L; 6 days) caused substantial alterations in the abundance of distinct G protein subunits. Concomitant with an enhanced expression of mu-opioid binding sites, the levels of the inhibitory G proteins Gi alpha 1 and Gi alpha 2 were found to be significantly increased. This coordinate up-regulation is accompanied by functional changes in mu-opioid receptor-stimulated low-Km GTPase, mu-receptor-mediated adenylate cyclase inhibition, and receptor-independent guanosine 5'-(beta gamma-imido)triphosphate [Gpp(NH)p; 10 nmol/L]-mediated attenuation of adenylate cyclase activity. In contrast, increased levels of inhibitory G proteins had no effect on muscarinic cholinergic receptor-mediated adenylate cyclase inhibition. With respect to stimulatory receptor systems, a reciprocal regulation was observed for prostaglandin E1 (PGE1) receptors and Gs alpha, the G protein subunit activating adenylate cyclase. RA treatment of SH-SY5Y cells increases both the number of PGE1 binding sites and PGE1-stimulated adenylate cyclase activity, but significantly reduced amounts of Gs alpha were found. This down-regulation is paralleled by a decrease in the stimulatory activity of Gs alpha as assessed in S49 cyc- reconstitution assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8133263

  9. Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronal cells.

    PubMed

    Mann, Amandeep; Tyndale, Rachel F

    2010-04-01

    Cytochrome P450 (CYP) 2D6 is an enzyme that is expressed in liver and brain. It can inactivate neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroisoquinoline and beta-carbolines. Genetically slow CYP2D6 metabolizers are at higher risk for developing Parkinson's disease, a risk that increases with exposure to pesticides. The goal of this study was to investigate the neuroprotective role of CYP2D6 in an in-vitro neurotoxicity model. SH-SY5Y human neuroblastoma cells express CYP2D6 as determined by western blotting, immunocytochemistry and enzymatic activity. CYP2D6 metabolized 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin and the CYP2D6-specific inhibitor quinidine (1 microM) blocked 96 +/- 1% of this metabolism, indicating that CYP2D6 is functional in this cell line. Treatment of cells with CYP2D6 inhibitors (quinidine, propanolol, metoprolol or timolol) at varying concentrations significantly increased the neurotoxicity caused by 1-methyl-4-phenylpyridinium (MPP+) at 10 and 25 microM by between 9 +/- 1 and 22 +/- 5% (P < 0.01). We found that CYP3A is also expressed in SH-SY5Y cells and inhibiting CYP3A with ketoconazole significantly increased the cell death caused by 10 and 25 microM of MPP+ by between 8 +/- 1 and 30 +/- 3% (P < 0.001). Inhibiting both CYP2D6 and CYP3A showed an additive effect on MPP+ neurotoxicity. These data further support a possible role for CYP2D6 in neuroprotection from Parkinson's disease-causing neurotoxins, especially in the human brain where expression of CYP2D6 is high in some regions (e.g. substantia nigra). PMID:20345925

  10. Does MW Radiation Affect Gene Expression, Apoptotic Level, and Cell Cycle Progression of Human SH-SY5Y Neuroblastoma Cells?

    PubMed

    Kayhan, Handan; Esmekaya, Meric Arda; Saglam, Atiye Seda Yar; Tuysuz, Mehmed Zahid; Canseven, Ayşe Gulnihal; Yagci, Abdullah Munci; Seyhan, Nesrin

    2016-06-01

    Neuroblastoma (NB) is a cancer that occurs in sympathetic nervous system arising from neuroblasts and nerve tissue of the adrenal gland, neck, chest, or spinal cord. It is an embryonal malignancy and affects infants and children. In this study, we investigated the effects of microwave (MW) radiation on apoptotic activity, cell viability, and cell cycle progression in human SH-SY5Y NB cells which can give information about MW radiation effects on neural cells covering the period from the embryonic stages to infants. SH-SY5Y NB cells were exposed to 2.1 GHz W-CDMA modulated MW radiation for 24 h at a specific absorption rate of 0.491 W/kg. Control samples were in the same conditions with MW-exposed samples but they were not exposed to MW radiation. The apoptotic activity of cells was measured by Annexin-V-FITC and propidium iodide staining. Moreover, mRNA levels of proliferative and cell cycle proteins were determined by real-time RT-PCR. The change in cell cycle progression was observed by using CycleTest-Plus DNA reagent. No significant change was observed in apoptotic activity of MW-exposed cells compared to control cells. The mRNA levels of c-myc and cyclin D1 were significantly reduced in MW group (p < 0.05). The percentage of MW-exposed cells in G1 phase was significantly higher than the percentage of control cells in G1 phase. MW radiation caused cell cycle arrest in G1 phase. These results showed that 2.1 GHz W-CDMA modulated MW radiation did not cause apoptotic cell death but changed cell cycle progression. PMID:27260669

  11. Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways

    PubMed Central

    Yan, Tingting; Zhao, Yan; Zhang, Xia; Lin, Xiaotong

    2016-01-01

    Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. Acetaldehyde, the most toxic metabolite of ethanol, mediates the brain tissue damage and cognitive dysfunction induced by chronic excessive alcohol consumption. In this study, the effect of astaxanthin, a marine bioactive compound, on acetaldehyde-induced cytotoxicity was investigated in SH-SY5Y cells. It was found that astaxanthin protected cells from apoptosis by ameliorating the effect of acetaldehyde on the expression of Bcl-2 family proteins, preventing the reduction of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bak induced by acetaldehyde. Further analyses showed that astaxanthin treatment inhibited acetaldehyde-induced reduction of the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). Astaxanthin treatment also prevented acetaldehyde-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK) and decrease of the level of activated extracellular signal-regulated kinases (ERKs). Activation of Akt/CREB pathway promotes cell survival and is involved in the upregulation of Bcl-2 gene. P38MAPK plays a critical role in apoptotic events while ERKs mediates the inhibition of apoptosis. Thus, astaxanthin may inhibit acetaldehyde-induced apoptosis through promoting the activation of Akt/CREB and ERKs and blocking the activation of p38MAPK. In addition, astaxanthin treatment suppressed the oxidative stress induced by acetaldehyde and restored the antioxidative capacity of SH-SY5Y cells. Therefore, astaxanthin may protect cells against acetaldehyde-induced cytotoxicity through maintaining redox balance and modulating apoptotic and survival signals. The results suggest that astaxanthin treatment may be beneficial for preventing neurotoxicity associated with acetaldehyde and excessive alcohol consumption. PMID:26978376

  12. Interferon Gamma potentiates the injury caused by MPP(+) on SH-SY5Y cells, which is attenuated by the nitric oxide synthases inhibition.

    PubMed

    Titze-de-Almeida, Simoneide S; Lustosa, Cátia Faria; Horst, Camila Hillesheim; Bel, Elaine Del; Titze-de-Almeida, Ricardo

    2014-12-01

    This study examined whether the cytokine interferon (IFN) gamma plays a role in the injury of SH-SY5Y cells caused by MPP(+) (1-methyl-4-phenylpyridinium). First of all, IFN-gamma sensitized cells to the neurotoxin MPP(+), as determined by MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide) assay. MPP(+)-injured cells showed higher reactive oxygen species (ROS) levels, which was reinforced by IFN-gamma. The injury triggered a marked expression of the neuronal NOS (nNOS) enzyme. L-NAME [N(ω)-nitro-L-arginine methyl ester, a non-specific NOS inhibitor] reestablished the cell viability after IFN-gamma challenging, and recovered cells from MPP(+) injury (95.0 vs. 84.7 %; P < 0.05). Seven-NI (7-nitroindazole, a nNOS inhibitor) protected cells against the injury by MPP(+) co-administered with IFN-gamma. Both inhibitors restrained the apoptosis of SH-SY5Y cells caused by MPP(+)/IFN-gamma. Regarding oxidative stress, L-NAME and 7-NI attenuated the increase in ROS levels caused by MPP(+) (45.3 or 48.4 vs. 87.9 %, P < 0.05). Indeed, L-NAME was more effective than 7-NI for reducing oxidative stress caused by MPP(+) under IFN-gamma exposition. The nNOS gene silencing by small-interfering RNAs recovered cells challenged by IFN-gamma (24 h), or MPP(+) (8 h). In conclusion, IFN-gamma sensitizes cells to MPP(+)-induced injury, also causing an increase in ROS levels. Pretreating cells with L-NAME or 7-NI reverts both the oxidative stress and apoptosis triggered by the neurotoxin MPP(+). Taking together, our data reinforce that IFN-gamma and NOS enzymes play a role in oxidative stress and dopaminergic cell death triggered by MPP(+). PMID:25297574

  13. Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways.

    PubMed

    Yan, Tingting; Zhao, Yan; Zhang, Xia; Lin, Xiaotong

    2016-03-01

    Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. Acetaldehyde, the most toxic metabolite of ethanol, mediates the brain tissue damage and cognitive dysfunction induced by chronic excessive alcohol consumption. In this study, the effect of astaxanthin, a marine bioactive compound, on acetaldehyde-induced cytotoxicity was investigated in SH-SY5Y cells. It was found that astaxanthin protected cells from apoptosis by ameliorating the effect of acetaldehyde on the expression of Bcl-2 family proteins, preventing the reduction of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bak induced by acetaldehyde. Further analyses showed that astaxanthin treatment inhibited acetaldehyde-induced reduction of the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). Astaxanthin treatment also prevented acetaldehyde-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK) and decrease of the level of activated extracellular signal-regulated kinases (ERKs). Activation of Akt/CREB pathway promotes cell survival and is involved in the upregulation of Bcl-2 gene. P38MAPK plays a critical role in apoptotic events while ERKs mediates the inhibition of apoptosis. Thus, astaxanthin may inhibit acetaldehyde-induced apoptosis through promoting the activation of Akt/CREB and ERKs and blocking the activation of p38MAPK. In addition, astaxanthin treatment suppressed the oxidative stress induced by acetaldehyde and restored the antioxidative capacity of SH-SY5Y cells. Therefore, astaxanthin may protect cells against acetaldehyde-induced cytotoxicity through maintaining redox balance and modulating apoptotic and survival signals. The results suggest that astaxanthin treatment may be beneficial for preventing neurotoxicity associated with acetaldehyde and excessive alcohol consumption. PMID:26978376

  14. Muscarinic receptor stimulation of D-aspartate uptake into human SH-SY5Y neuroblastoma cells is attenuated by hypoosmolarity.

    PubMed

    Foster, Daniel J; Heacock, Anne M; Fisher, Stephen K

    2010-04-01

    In addition to its function as an excitatory neurotransmitter, glutamate plays a major role as an osmolyte within the central nervous system (CNS). Accordingly, mechanisms that regulate glutamate release and uptake are of physiological importance not only during conditions in which cell volume remains constant but also when cells are subjected to hypoosmotic stress. In the present study, the ability of muscarinic cholinergic receptors (mAChRs) to regulate the uptake of glutamate (monitored as D-aspartate) into human SH-SY5Y neuroblastoma cells under isotonic or hypotonic conditions has been examined. In isotonic media, agonist activation of mAChRs resulted in a significant increase (250-300% of control) in the uptake of D-aspartate and, concurrently, a cellular redistribution of the excitatory amino acid transporter 3 (EAAT3) to the plasma membrane. mAChR-mediated increases in d-aspartate uptake were potently blocked by the EAAT3 inhibitor l-beta-threo-benzyl-aspartate. In hypotonic media, the ability of mAChR activation to facilitate D-aspartate uptake was significantly attenuated (40-50%), and the cellular distribution of EAAT3 was disrupted. Reduction of mAChR-stimulated D-aspartate uptake under hypoosmotic conditions could be fully reversed upon re-exposure of the cells to isotonic media. Under both isotonic and hypotonic conditions, mAChR-mediated increases in D-aspartate uptake depended on cytoskeletal integrity, protein kinase C and phosphatidylinositol 3-kinase activities, and the availability of intracellular Ca2+. In contrast, dependence on extracellular Ca2+ was observed only under isotonic conditions. The results suggest that, although the uptake of D-aspartate into SH-SY5Y cells is enhanced after mAChR activation, this process is markedly attenuated by hypoosmolarity. PMID:20080957

  15. Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

    PubMed Central

    Luukkonen, Jukka; Liimatainen, Anu; Höytö, Anne; Juutilainen, Jukka; Naarala, Jonne

    2011-01-01

    Background Extremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells. Methodology/Principal Findings Exposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone. Conclusions The results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome. PMID:21448285

  16. Decline in c-myc mRNA expression but not the induction of c-fos mRNA expression is associated with differentiation of SH-SY5Y human neuroblastoma cells

    SciTech Connect

    Jalava, A.M.; Heikkilae, J.E.; Akerman, K.E.O. )

    1988-11-01

    The induction of differentiation in SH-SY5Y human neuroblastoma cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is accompanied by a rapid and a transient expression of c-fos mRNA and a down-regulation of c-myc RNA. The TPA-induced expression of c-fos mRNA was inhibited by H-7, a specific inhibitor of protein kinase C (PK-C). Dioctanoylglycerol (DiC{sub 8}) failed to induce differentiation of SH-SY5Y cells or to down-regulate c-myc mRNA but it did induce the expression of c-fos mRNA. Treatment of IMR-32 human neuroblastoma cells with TPA did not cause differentiation although c-fos mRNA was induced. Since PK-C in SH-SY5Y cells was activated by both TPA and DiC{sub 8} it is suggested that the activation of PK-C alone is not sufficient to induce differentiation in SH-SY5Y cells. The down-regulation of c-myc mRNA rather than the induction of c-fos mRNA seems to be associated with differentiation process in SH-SY5Y cells.

  17. Terrestrial Ages of Antarctic Meteorites: Up Date 1999

    NASA Technical Reports Server (NTRS)

    Nishiizumi, K.; Caffee, M. W.; Welten, K. C.

    2000-01-01

    We are continuing our ongoing study of cosmogenic nuclides in Antarctic meteorites. In addition to the studies of exposure histories of meteorites, we study terrestrial ages and pairing of Antarctic meteorites and desert meteorites. Terrestrial ages of Antarctic meteorites provide information on meteorite accumulation mechanisms, mean weathering lifetimes, and influx rates. The determination of Cl-36 (half-life=3.01 x 10(exp 5) y) terrestrial ages is one of our long-term on-going projects, however, in many instances neither Cl-36 or C-14 (5,730 y) yields an accurate terrestrial age. Using Ca-41 (1.04 x 10(exp 5) y) for terrestrial age determinations solves this problem by filling the gap in half-life between C-14 and Cl-36 ages. We are now applying the new Ca-41 - Cl-36 terrestrial age method as well as the Cl-36 - Be-10 method to Antarctic meteorites. Our measurements and C-14 terrestrial age determinations by the University of Arizona group are always complementary.

  18. Healthy Aging

    MedlinePlus

    ... About Us Contact Us Text size | Print | Healthy Aging This information in Spanish ( en español ) A healthy ... Aging email updates. Enter email address Submit Healthy Aging news Accessibility | Privacy policy | Disclaimers | FOIA | Link to ...

  19. Healthy Aging

    MedlinePlus

    ... A Change Contrast print sign up Share Healthy Aging This category offers tips on how to stay ... with Smell Problems with Taste Skin Care and Aging Sleep and Aging Taking Medicines Talking with Your ...

  20. The aging mouse partially models the aging human spine: lumbar and coccygeal disc height, composition, mechanical properties, and Wnt signaling in young and old mice

    PubMed Central

    Aguilar, Rhiannon; Harland, Robin A.; Bomar, Bradley A.; Silva, Matthew J.

    2014-01-01

    Murine lumbar and coccygeal (tail) regions of spines are commonly used to study cellular signaling of age-related disc diseases, but the tissue-level changes of aging intervertebral discs and vertebrae of each spinal region remain unclear. Furthermore, the impact of aging lumbar and coccygeal discs on Wnt/β-catenin signaling, which is putatively involved in the catabolism of intervertebral discs, is also unclear. We compared disc/vertebrae morphology and mechanics and biochemical composition of intervertebral discs from lumbar and coccygeal regions between young (4–5 mo) and old (20–22 mo) female C57BL/6 mice. Center intervertebral disc height from both regions was greater in old discs than young discs. Compared with young, old lumbar discs had a lower early viscous coefficient (a measure of stiffness) by 40%, while conversely old coccygeal discs were stiffer by 53%. Biochemically, old mice had double the collagen content in lumbar and coccygeal discs of young discs, greater glycosaminoglycan in lumbar discs by 37%, but less glycosaminoglycan in coccygeal discs by 32%. Next, we compared Wnt activity of lumbar and coccygeal discs of 4- to 5-mo and 12- to 14-mo TOPGAL mice. Despite the disc-specific changes, aging decreased Wnt signaling in the nucleus pulposus from both spinal regions by ≥64%. Compared with young, trabecular bone volume/tissue volume and ultimate force were less in old lumbar vertebrae, but greater in old coccygeal vertebrae. Thus intervertebral discs and vertebrae age in a spinal region-dependent manner, but these differential age-related changes may be uncoupled from Wnt signaling. Overall, lumbar and coccygeal regions are not interchangeable in modeling human aging. PMID:24790018

  1. A role for protein kinase C subtypes alpha and epsilon in phorbol-ester-enhanced K(+)- and carbachol-evoked noradrenaline release from the human neuroblastoma SH-SY5Y.

    PubMed Central

    Turner, N A; Rumsby, M G; Walker, J H; McMorris, F A; Ball, S G; Vaughan, P F

    1994-01-01

    Protein kinase C (PKC) consists of a family of closely related subtypes which differ in their localization and activation properties. Our previous studies have suggested a role for PKC in the regulation of noradrenaline (NA) release from the human neuroblastoma SH-SY5Y. Here we have used two approaches to characterize the PKC subtypes present in SH-SY5Y cells. Firstly, the PCR was used to show that SH-SY5Y cells contain mRNA encoding PKC subtypes alpha, beta, gamma, delta, epsilon and zeta. Secondly, immunoblotting showed that SH-SY5Y cells express PKC subtypes alpha, epsilon and zeta at the protein level. Prolonged (48 h) exposure of cells to the phorbol ester phorbol 12-myristate 13-acetate (PMA; 100 nM) resulted in a marked decrease in the amounts of PKC-alpha and PKC-epsilon, with no change in levels of PKC-zeta. Prolonged PMA treatment had no significant effect on K(+)-evoked NA release from SH-SY5Y cells, whereas carbachol-evoked release was increased 2.2-fold. However, prolonged exposure to PMA completely inhibited the ability of acute (12 min) PMA treatment to enhance both K(+)- and carbachol-evoked NA release. The specific PKC inhibitor RO 31-7459 (10 microM) was found to inhibit K(+)- and carbachol-evoked release by 27% and 68% respectively. RO 31-7549 also completely inhibited the ability of acute PMA treatment to enhance release. These data suggest that PKC-alpha and/or PKC-epsilon play an essential role in the regulation of PMA-enhanced K(+)- and carbachol-evoked NA release in SH-SY5Y cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8297348

  2. Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

    SciTech Connect

    Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K.

    2012-08-01

    Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-{kappa}B), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

  3. Clinacanthus nutans Extracts Modulate Epigenetic Link to Cytosolic Phospholipase A2 Expression in SH-SY5Y Cells and Primary Cortical Neurons.

    PubMed

    Tan, Charlene Siew-Hon; Ho, Christabel Fung-Yih; Heng, Swan-Ser; Wu, Jui-Sheng; Tan, Benny Kwong-Huat; Ng, Yee-Kong; Sun, Grace Y; Lin, Teng-Nan; Ong, Wei-Yi

    2016-09-01

    Clinacanthus nutans Lindau (C. nutans), commonly known as Sabah Snake Grass in southeast Asia, is widely used in folk medicine due to its analgesic, antiviral, and anti-inflammatory properties. Our recent study provided evidence for the regulation of cytosolic phospholipase A2 (cPLA2) mRNA expression by epigenetic factors (Tan et al. in Mol Neurobiol. doi: 10.1007/s12035-015-9314-z , 2015). This enzyme catalyzes the release of arachidonic acid from glycerophospholipids, and formation of pro-inflammatory eicosanoids or toxic lipid peroxidation products such as 4-hydroxynonenal. In this study, we examined the effects of C. nutans ethanol leaf extracts on epigenetic regulation of cPLA2 mRNA expression in SH-SY5Y human neuroblastoma cells and mouse primary cortical neurons. C. nutans modulated induction of cPLA2 expression in SH-SY5Y cells by histone deacetylase (HDAC) inhibitors, MS-275, MC-1568, and TSA. C. nutans extracts also inhibited histone acetylase (HAT) activity. Levels of cPLA2 mRNA expression were increased in primary cortical neurons subjected to 0.5-h oxygen-glucose deprivation injury (OGD). This increase was significantly inhibited by C. nutans treatment. Treatment of primary neurons with the HDAC inhibitor MS-275 augmented OGD-induced cPLA2 mRNA expression, and this increase was modulated by C. nutans extracts. OGD-stimulated increase in cPLA2 mRNA expression was also reduced by a Tip60 HAT inhibitor, NU9056. In view of a key role of cPLA2 in the production of pro-inflammatory eicosanoids and free radical damage, and the fact that epigenetic effects on genes are often long-lasting, results suggest a role for C. nutans and phytochemicals to inhibit the production of arachidonic acid-derived pro-inflammatory eicosanoids and chronic inflammation, through epigenetic regulation of cPLA2 expression. PMID:27319010

  4. TIRFM and pH-sensitive GFP-probes to evaluate neurotransmitter vesicle dynamics in SH-SY5Y neuroblastoma cells: cell imaging and data analysis.

    PubMed

    Daniele, Federica; Di Cairano, Eliana S; Moretti, Stefania; Piccoli, Giovanni; Perego, Carla

    2015-01-01

    Synaptic vesicles release neurotransmitters at chemical synapses through a dynamic cycle of fusion and retrieval. Monitoring synaptic activity in real time and dissecting the different steps of exo-endocytosis at the single-vesicle level are crucial for understanding synaptic functions in health and disease. Genetically-encoded pH-sensitive probes directly targeted to synaptic vesicles and Total Internal Reflection Fluorescence Microscopy (TIRFM) provide the spatio-temporal resolution necessary to follow vesicle dynamics. The evanescent field generated by total internal reflection can only excite fluorophores placed in a thin layer (<150 nm) above the glass cover on which cells adhere, exactly where the processes of exo-endocytosis take place. The resulting high-contrast images are ideally suited for vesicles tracking and quantitative analysis of fusion events. In this protocol, SH-SY5Y human neuroblastoma cells are proposed as a valuable model for studying neurotransmitter release at the single-vesicle level by TIRFM, because of their flat surface and the presence of dispersed vesicles. The methods for growing SH-SY5Y as adherent cells and for transfecting them with synapto-pHluorin are provided, as well as the technique to perform TIRFM and imaging. Finally, a strategy aiming to select, count, and analyze fusion events at whole-cell and single-vesicle levels is presented. To validate the imaging procedure and data analysis approach, the dynamics of pHluorin-tagged vesicles are analyzed under resting and stimulated (depolarizing potassium concentrations) conditions. Membrane depolarization increases the frequency of fusion events and causes a parallel raise of the net fluorescence signal recorded in whole cell. Single-vesicle analysis reveals modifications of fusion-event behavior (increased peak height and width). These data suggest that potassium depolarization not only induces a massive neurotransmitter release but also modifies the mechanism of vesicle

  5. Cross-Sectional and Longitudinal Associations between Household Food Security and Child Anthropometry at Ages 5 and 8 Years in Ethiopia, India, Peru, and Vietnam123

    PubMed Central

    Humphries, Debbie L; Dearden, Kirk A; Crookston, Benjamin T; Fernald, Lia C; Stein, Aryeh D; Woldehanna, Tassew; Penny, Mary E; Behrman, Jere R

    2015-01-01

    Background: Poor childhood nutritional status has lifetime effects and food insecurity is associated with dietary practices that can impair nutritional status. Objectives: We assessed concurrent and subsequent associations between food insecurity and height-for-age z scores (HAZs) and body mass index–for-age z scores (BMI-Zs); evaluated associations with transitory and chronic food insecurity; and tested whether dietary diversity mediates associations between food insecurity and nutritional status. Methods: We used data from the Young Lives younger cohort composed of children in Ethiopia (n = 1757), India (n = 1825), Peru (n = 1844), and Vietnam (n = 1828) recruited in 2002 (round 1) at ∼1 y old, with subsequent data collection at 5 y in 2006 (round 2) and 8 y in 2009 (round 3). Results: Children from food-insecure households had significantly lower HAZs in all countries at 5 y (Ethiopia, −0.33; India, −0.53; Peru, −0.31; and Vietnam, −0.68 HAZ; all P < 0.001), although results were attenuated after controlling for potential confounders (Ethiopia, −0.21; India, −0.32; Peru, −0.14; and Vietnam, −0.27 HAZ; P < 0.01). Age 5 y food insecurity predicted the age 8 y HAZ, but did not add predictive power beyond HAZ at age 5 y in Ethiopia, India, or Peru. Age 5 y food insecurity predicted the age 8 y BMI-Z even after controlling for the 5 y BMI-Z, although associations were not significant after the inclusion of additional confounding variables (Ethiopia, P = 0.12; India, P = 0.29; Peru, P = 0.16; and Vietnam, P = 0.51). Chronically food-insecure households had significantly lower HAZs than households that were consistently food-secure, although BMI-Zs did not differ by chronic food-insecurity status. Dietary diversity mediated 18.8–30.5% of the association between food security and anthropometry in Vietnam, but mediated to a lesser degree (8.4–19.3%) in other countries. Conclusions: In 4 countries, food insecurity at 5 y of age was associated with

  6. Antioxidant phenolic profile from ethyl acetate fraction of Fructus Ligustri Lucidi with protection against hydrogen peroxide-induced oxidative damage in SH-SY5Y cells.

    PubMed

    Ju, Heng-Yin; Chen, Shiu Ching; Wu, Kuo-Jen; Kuo, Hui-Chun; Hseu, You-Cheng; Ching, Hui; Wu, Chi-Rei

    2012-03-01

    In this study, we demonstrated the antioxidant and protective properties of crude extract and fractions from Fructus Ligustri Lucidi (FLL) against hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells. The contents of their phytochemical profiles were determined by spectrophotometric methods and high performance liquid chromatography using a photodiode array detector. FLL crude extract possessed appreciable scavenging capacity against 1,1-diphenyl-2-picrylhydrazyl and H2O2. The ethyl acetate (EtOAc) fraction was the most active fraction in scavenging free radicals and H2O2. Following exposure of cells to H2O2, there was a marked decrease in cell survival and intracellular antioxidant enzymes, and then intracellular oxidative stress, the level of lipid peroxidation, and caspase-3 activity were increased. Simultaneous treatment with the EtOAc fraction blocked these H2O2-induced cellular events. Hydroxytyrosol and salidroside are major components of the EtOAc fraction. These results show that the phenolic-enriched EtOAc fraction of FLL contains tyrosol-related derivatives and exerts the protective effects against H2O2 toxicity via its free radical scavenging activity and ability to elevate the levels of antioxidant enzymes. PMID:22142696

  7. Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells

    PubMed Central

    Unoki, Takamitsu; Abiko, Yumi; Toyama, Takashi; Uehara, Takashi; Tsuboi, Koji; Nishida, Motohiro; Kaji, Toshiyuki; Kumagai, Yoshito

    2016-01-01

    Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as “S-mercuration”, potentially resulting in modulation of the cellular signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved in cell survival. Exposure of human neuroblastoma SH-SY5Y cells of up to 2 μM MeHg phosphorylated Akt and its downstream signal molecule CREB, presumably due to inactivation of PTEN through S-mercuration. As a result, the anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation of Akt/CREB/Bcl-2 signaling mediated by MeHg was, at least in part, linked to cellular defence because either pretreatment with wortmannin to block PI3K/Akt signaling or knockdown of Bcl-2 enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations of MeHg disrupted Akt/CREB/Bcl-2 signaling. This phenomenon was attributed to S-mercuration of CREB through Cys286 rather than Akt. These results suggest that although MeHg is an apoptosis-inducing toxicant, this environmental electrophile is able to activate the cell survival signal transduction pathway at lower concentrations prior to apoptotic cell death. PMID:27357941

  8. Protective effects of Arctium lappa L. roots against hydrogen peroxide-induced cell injury and potential mechanisms in SH-SY5Y cells.

    PubMed

    Tian, Xing; Guo, Li-Ping; Hu, Xiao-Long; Huang, Jin; Fan, Yan-Hua; Ren, Tian-Shu; Zhao, Qing-Chun

    2015-04-01

    Accumulated evidence has shown that excessive reactive oxygen species (ROS) have been implicated in neuronal cell death related with various chronic neurodegenerative disorders. This study was designed to explore neuroprotective effects of ethyl acetate extract of Arctium lappa L. roots (EAL) on hydrogen peroxide (H2O2)-induced cell injury in human SH-SY5Y neuroblastoma cells. The cell viability was significantly decreased after exposure to 200 μM H2O2, whereas pretreatment with different concentrations of EAL attenuated the H2O2-induced cytotoxicity. Hoechst 33342 staining indicated that EAL reversed nuclear condensation in H2O2-treated cells. Meanwhile, TUNEL assay with DAPI staining showed that EAL attenuated apoptosis was induced by H2O2. Pretreatment with EAL also markedly elevated activities of antioxidant enzyme (GSH-Px and SOD), reduced lipid peroxidation (MDA) production, prevented ROS formation, and the decrease of mitochondrial membrane potential. In addition, EAL showed strong radical scavenging ability in 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays. Furthermore, EAL inhibited H2O2-induced apoptosis by increases in the Bcl-2/Bax ratio, decreases in cytochrome c release, and attenuation of caspase-3, caspase-9 activities, and expressions. These findings suggest that EAL may be regarded as a potential antioxidant agent and possess potent neuroprotective activity against H2O2-induced injury. PMID:25352420

  9. Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line.

    PubMed

    Shiohira, Hideo; Kitaoka, Akira; Enjoji, Munechika; Uno, Tsukasa; Nakashima, Manabu

    2012-01-01

    Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity. PMID:23124249

  10. Impact of plant extracts tested in attention-deficit/hyperactivity disorder treatment on cell survival and energy metabolism in human neuroblastoma SH-SY5Y cells.

    PubMed

    Schmidt, Andreas Johannes; Krieg, Jürgen-Christian; Hemmeter, Ulrich Michael; Kircher, Tilo; Schulz, Eberhard; Clement, Hans-Willi; Heiser, Philip

    2010-10-01

    Plant extracts such as Hypericum perforatum and Pycnogenol have been tested as alternatives to the classical ADHD drugs. It has been possible to describe neuroprotective effects of such plant extracts. A reduction of ADHD symptoms could be shown in clinical studies after the application of Pycnogenol, which is a pine bark extract. The impacts of the standardized herbal extracts Hypericum perforatum, Pycnogenol and Enzogenol up to a concentration of 5000 ng/mL on cell survival and energy metabolism in human SH-SY5Y neuroblastoma cells has been investigated in the present examination. Hypericum perforatum significantly decreased the survival of cells after treatment with a concentration of 5000 ng/mL, whereas lower concentrations exerted no significant effects. Pycnogenol( induced a significant increase of cell survival after incubation with a concentration of 32.25 ng/mL and a concentration of 250 ng/mL. Other applied concentrations of Pycnogenol failed to exert significant effects. Treatment with Enzogenol did not lead to significant changes in cell survival.Concerning energy metabolism, the treatment of cells with a concentration of 5000 ng/mL Hypericum perforatum led to a significant increase of ATP levels, whereas treatment with a concentration of 500 ng/mL had no significant effect. Incubation of cells with Pycnogenol and Enzogenol exerted no significant effects.None of the tested substances caused any cytotoxic effect when used in therapeutically relevant concentrations. PMID:20878709

  11. Carnosic acid attenuates apoptosis induced by amyloid-β 1-42 or 1-43 in SH-SY5Y human neuroblastoma cells.

    PubMed

    Meng, Pengfei; Yoshida, Hidemi; Tanji, Kunikazu; Matsumiya, Tomoh; Xing, Fei; Hayakari, Ryo; Wang, Liang; Tsuruga, Kazushi; Tanaka, Hiroshi; Mimura, Junsei; Kosaka, Kunio; Itoh, Ken; Takahashi, Ippei; Kawaguchi, Shogo; Imaizumi, Tadaatsu

    2015-05-01

    Amyloid-beta (Aβ) peptides, Aβ 1-42 (Aβ42) and Aβ43 in particular, cause neurotoxicity and cell death in the brain of Alzheimer's disease (AD) at higher concentrations. Carnosic acid (CA), a phenolic diterpene compound in the labiate herbs rosemary and sage, serves as an activator for neuroprotective and neurotrophic functions in brain cells. We investigated the effect of CA on apoptosis induced by Aβ42 or Aβ43 in cultured SH-SY5Y human neuroblastoma cells. Treatment of the cells with Aβ42 or Aβ43 (monomer, 10 μM each) induced apoptosis, which was confirmed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF). Concurrently, the Aβ treatment induced the activation of caspase (Casp) cascades including an effector Casp (Casp3) and initiator Casps (Casp4, Casp8 and Casp9). Pretreatment of the cells with CA (10 μM) partially attenuated the apoptosis induced by Aβ42 or Aβ43. CA pretreatment also reduced the cellular oligomers of Aβ42 and Aβ43. These results suggest that CA suppressed the activation of Casp cascades by reducing the intracellular oligomerization of exogenous Aβ42/43 monomer. The ingestion of an adequate amount of CA may have a potential in the prevention of Aβ-mediated diseases, particularly AD. PMID:25510380

  12. The Role of Neurotransmitters in Protection against Amyloid- β Toxicity by KiSS-1 Overexpression in SH-SY5Y Neurons.

    PubMed

    Chilumuri, Amrutha; Milton, Nathaniel G N

    2013-01-01

    Recent studies have suggested that the kisspeptin (KP) and kissorphin (KSO) peptides have neuroprotective actions against the Alzheimer's amyloid- β (A β ) peptide. Overexpression of the human KiSS-1 gene that codes for KP and KSO peptides in SH-SY5Y neurons has also been shown to inhibit A β neurotoxicity. The in vivo actions of KP include activation of neuroendocrine and neurotransmitter systems. The present study used antagonists of KP, neuropeptide FF (NPFF), opioids, oxytocin, estrogen, adrenergic, cholinergic, dopaminergic, serotonergic, and γ -aminobutyric acid (GABA) receptors plus inhibitors of catalase, cyclooxygenase, nitric oxide synthase, and the mitogen activated protein kinase cascade to characterize the KiSS-1 gene overexpression neuroprotection against A β cell model. The results showed that KiSS-1 overexpression is neuroprotective against A β and the action appears to involve the KP or KSO peptide products of KiSS-1 processing. The mechanism of neuroprotection does not involve the activation of the KP or NPFF receptors. Opioids play a role in the toxicity of A β in the KiSS-1 overexpression system and opioid antagonists naloxone or naltrexone inhibited A β toxicity. The mechanism of KiSS-1 overexpression induced protection against A β appears to have an oxytocin plus a cyclooxygenase dependent component, with the oxytocin antagonist atosiban and the cyclooxygenase inhibitor SC-560 both enhancing the toxicity of A β . PMID:24967306

  13. The Role of Neurotransmitters in Protection against Amyloid-β Toxicity by KiSS-1 Overexpression in SH-SY5Y Neurons

    PubMed Central

    Milton, Nathaniel G. N.

    2013-01-01

    Recent studies have suggested that the kisspeptin (KP) and kissorphin (KSO) peptides have neuroprotective actions against the Alzheimer's amyloid-β (Aβ) peptide. Overexpression of the human KiSS-1 gene that codes for KP and KSO peptides in SH-SY5Y neurons has also been shown to inhibit Aβ neurotoxicity. The in vivo actions of KP include activation of neuroendocrine and neurotransmitter systems. The present study used antagonists of KP, neuropeptide FF (NPFF), opioids, oxytocin, estrogen, adrenergic, cholinergic, dopaminergic, serotonergic, and γ-aminobutyric acid (GABA) receptors plus inhibitors of catalase, cyclooxygenase, nitric oxide synthase, and the mitogen activated protein kinase cascade to characterize the KiSS-1 gene overexpression neuroprotection against Aβ cell model. The results showed that KiSS-1 overexpression is neuroprotective against Aβ and the action appears to involve the KP or KSO peptide products of KiSS-1 processing. The mechanism of neuroprotection does not involve the activation of the KP or NPFF receptors. Opioids play a role in the toxicity of Aβ in the KiSS-1 overexpression system and opioid antagonists naloxone or naltrexone inhibited Aβ toxicity. The mechanism of KiSS-1 overexpression induced protection against Aβ appears to have an oxytocin plus a cyclooxygenase dependent component, with the oxytocin antagonist atosiban and the cyclooxygenase inhibitor SC-560 both enhancing the toxicity of Aβ. PMID:24967306

  14. Hypoxia-inducible factor-1α upregulates tyrosine hydroxylase and dopamine transporter by nuclear receptor ERRγ in SH-SY5Y cells.

    PubMed

    Lim, Juhee; Kim, Hyo-In; Bang, Yeojin; Seol, Wongi; Choi, Hueng-Sik; Choi, Hyun Jin

    2015-04-15

    Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor relevant to the development of many mammalian organs including the brain. However, the molecular mechanisms by which signaling events mediate neuronal differentiation have not been fully elucidated. In the present study, we show for the first time that the orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated by HIF-1α and plays essential roles in HIF-1α-induced upregulation of dopaminergic marker molecules such as tyrosine hydroxylase and dopamine transporter. We found that deferoxamine upregulated HIF-1α and enhanced the dopaminergic phenotype and neurite outgrowth of SH-SY5Y cells. Deferoxamine activated transcription and protein expression of ERRγ, and deferoxamine-induced upregulation of tyrosine hydroxylase and dopamine transporter was attenuated by using the ERRγ inverse agonist or silencing ERRγ. Altogether, these results suggest that HIF-1α can positively regulate the dopaminergic phenotype through ERRγ. This study could provide new perspectives for understanding the mechanisms underlying the promotion of dopaminergic neuronal differentiation by hypoxia. PMID:25807177

  15. The effects of okra (Abelmoschus esculentus Linn.) on the cellular events associated with Alzheimer's disease in a stably expressed HFE neuroblastoma SH-SY5Y cell line.

    PubMed

    Mairuae, Nootchanat; Connor, James R; Lee, Sang Y; Cheepsunthorn, Poonlarp; Tongjaroenbuangam, Walaiporn

    2015-08-31

    It has been reported that persons carrying the H63D variant in their hemochromatosis (HFE) gene are at increased risk of Alzheimer's disease (AD). We investigated the possibility that okra (Abelmoschus esculentus) and quercetin could mitigate this risk factor by examining its effect on AD-associated cellular events in HFE stably expressing SH-SY5Y cells. Treatment of H63D HFE cells either with okra or quercetin significantly decreased reactive oxygen species (ROS), hydrogen peroxide (H2O2), and protein oxidation compared to untreated cells. The levels of tau phosphorylation at serine-199, serine-202, and serine-396 sites were also significantly decreased when cells were treated with okra. Exposure of the H63D and wild type (WT) cells to iron increased tau phosphorylation, but this response was decreased significantly when cells were treated with okra. The mechanism responsible for these changes appears to be related to decreased glycogen synthase kinase (GSK)-3β activity, an upstream signaling kinase of tau phosphorylation. We also established that okra treatment dramatically decreases intracellular iron levels in H63D cells compared to untreated cells. Our results provide important in vitro data on the effects of okra on various AD-associated cellular processes in H63D variant HFE cells. These results suggest okra may be beneficial in people expressing the H63D variant to reduce the risk of AD and other neurodegenerative diseases related to oxidative stress. Further in vivo studies would help confirm this. PMID:26170247

  16. Lycopene protects human SH‑SY5Y neuroblastoma cells against hydrogen peroxide‑induced death via inhibition of oxidative stress and mitochondria‑associated apoptotic pathways.

    PubMed

    Feng, Chunsheng; Luo, Tianfei; Zhang, Shuyan; Liu, Kai; Zhang, Yanhong; Luo, Yinan; Ge, Pengfei

    2016-05-01

    Oxidative stress, which is characterized by excessive production of reactive oxygen species (ROS), is a common pathway that results in neuronal injury or death due to various types of pathological stress. Although lycopene has been identified as a potent antioxidant, its effect on hydrogen peroxide (H2O2)‑induced neuronal damage remains unclear. In the present study, pretreatment with lycopene was observed to protect SH‑SY5Y neuroblastoma cells against H2O2‑induced death via inhibition of apoptosis resulting from activation of caspase‑3 and translocation of apoptosis inducing factor (AIF) to the nucleus. Furthermore, the over‑produced ROS, as well as the reduced activities of anti‑oxidative enzymes, superoxide dismutase and catalase, were demonstrated to be alleviated by lycopene. Additionally, lycopene counteracted H2O2‑induced mitochondrial dysfunction, which was evidenced by suppression of mitochondrial permeability transition pore opening, attenuation of the decline of the mitochondrial membrane potential, and inhibition of the increase of Bax and decrease of Bcl‑2 levels within the mitochondria. The release of cytochrome c and AIF from the mitochondria was also reduced. These results indicate that lycopene is a potent neuroprotectant against apoptosis, oxidative stress and mitochondrial dysfunction, and could be administered to prevent neuronal injury or death. PMID:27035331

  17. Cellular Stress and p53-Associated Apoptosis by Juniperus communis L. Berry Extract Treatment in the Human SH-SY5Y Neuroblastoma Cells

    PubMed Central

    Lantto, Tiina A.; Laakso, Into; Dorman, H. J. Damien; Mauriala, Timo; Hiltunen, Raimo; Kõks, Sulev; Raasmaja, Atso

    2016-01-01

    Plant phenolics have shown to activate apoptotic cell death in different tumourigenic cell lines. In this study, we evaluated the effects of juniper berry extract (Juniperus communis L.) on p53 protein, gene expression and DNA fragmentation in human neuroblastoma SH-SY5Y cells. In addition, we analyzed the phenolic composition of the extract. We found that juniper berry extract activated cellular relocalization of p53 and DNA fragmentation-dependent cell death. Differentially expressed genes between treated and non-treated cells were evaluated with the cDNA-RDA (representational difference analysis) method at the early time point of apoptotic process when p53 started to be activated and no caspase activity was detected. Twenty one overexpressed genes related to cellular stress, protein synthesis, cell survival and death were detected. Interestingly, they included endoplasmic reticulum (ER) stress inducer and sensor HSPA5 and other ER stress-related genes CALM2 and YKT6 indicating that ER stress response was involved in juniper berry extract mediated cell death. In composition analysis, we identified and quantified low concentrations of fifteen phenolic compounds. The main groups of them were flavones, flavonols, phenolic acids, flavanol and biflavonoid including glycosides of quercetin, apigenin, isoscutellarein and hypolaetin. It is suggested that juniper berry extract induced the p53-associated apoptosis through the potentiation and synergism by several phenolic compounds. PMID:27420050

  18. Comprehensive profiling of the cell surface proteome of Sy5Y neuroblastoma cells yields a subset of proteins associated with tumor differentiation.

    PubMed

    Garcia, Jacob; Faca, Vitor; Jarzembowski, Jason; Zhang, Qing; Park, Julie; Hanash, Samir

    2009-08-01

    Neuroblastoma tumors are derived from the neural crest and exhibit substantial phenotypic heterogeneity and various degrees of differentiation and maturation. The identification of new cell surface markers in neuroblastoma has relevance to disease classification and therapy. As a means to categorize neuroblastomas based on cell surface protein expression, we have obtained a comprehensive profile of the cell surface proteome of the MYCN nonamplified SH-SY5Y neuroblastoma cell line. Biotinylated cell surface proteins were captured using an avidin affinity column, fractionated by reversed-phase chromatography and subjected to in-depth analysis by LC-MS/MS. An extensive list of proteins was established and a subset of surface membrane proteins was assessed by immunohistochemistry in a set of neuroblastoma tissue microarrays. Among identified proteins tested, NCAM and CD147 exhibited increased expression in poorly differentiated tumors (p < 0.01 and <0.03, respectively). CD147 expression was previously associated with aggressive carcinomas but has not been described in neuroblastoma. This comprehensive neuroblastoma cell surface profile has identified novel potential markers for neuroblastoma classification and novel potential targets for therapy. PMID:19505085

  19. Tau dephosphorylation and microfilaments disruption are upstream events of the anti-proliferative effects of DADS in SH-SY5Y cells

    PubMed Central

    Aquilano, Katia; Vigilanza, Paola; Filomeni, Giuseppe; Rotilio, Giuseppe; Ciriolo, Maria R

    2010-01-01

    Abstract Garlic organosulphur compounds have been successfully used as redox anti-proliferative agents. In this work, we dissect the effects of diallyl disulphide (DADS) focusing on the events upstream of cell cycle arrest and apoptosis induced in neuroblastoma SH-SY5Y cells. We demonstrate that DADS is able to cause early morphological changes, cytoskeleton oxidation, microfilaments reduction and depolymerization of microtubules. These events are attenuated in cells stably overexpressing the antioxidant enzyme SOD1, suggesting that superoxide plays a crucial role in destabilizing cytoskeleton. Moreover, we evidence that the main microtubules-associated protein Tau undergoes PP1-mediated dephosphorylation as demonstrated by treatment with okadaic acid as well as by immunoreaction with anti-Tau-1 antibody, which specifically recognizes its dephosphorylated forms. Tau dephosphorylation is inhibited by the two-electron reductants NAC and GSH ester but not by SOD1. The inability of DADS to induce apoptosis in neuroblastoma-differentiated cells gives emphasis to the anti-proliferative activity of DADS, which can be regarded as a promising potent anti-neuroblastoma drug by virtue of its widespread cytoskeleton disrupting action on proliferating cells. PMID:19040422

  20. Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells.

    PubMed

    Unoki, Takamitsu; Abiko, Yumi; Toyama, Takashi; Uehara, Takashi; Tsuboi, Koji; Nishida, Motohiro; Kaji, Toshiyuki; Kumagai, Yoshito

    2016-01-01

    Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as "S-mercuration", potentially resulting in modulation of the cellular signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved in cell survival. Exposure of human neuroblastoma SH-SY5Y cells of up to 2 μM MeHg phosphorylated Akt and its downstream signal molecule CREB, presumably due to inactivation of PTEN through S-mercuration. As a result, the anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation of Akt/CREB/Bcl-2 signaling mediated by MeHg was, at least in part, linked to cellular defence because either pretreatment with wortmannin to block PI3K/Akt signaling or knockdown of Bcl-2 enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations of MeHg disrupted Akt/CREB/Bcl-2 signaling. This phenomenon was attributed to S-mercuration of CREB through Cys286 rather than Akt. These results suggest that although MeHg is an apoptosis-inducing toxicant, this environmental electrophile is able to activate the cell survival signal transduction pathway at lower concentrations prior to apoptotic cell death. PMID:27357941

  1. Aluminium inhibits muscarinic agonist-induced inositol 1,4,5-trisphosphate production and calcium mobilization in permeabilized SH-SY5Y human neuroblastoma cells.

    PubMed

    Wood, P C; Wojcikiewicz, R J; Burgess, J; Castleden, C M; Nahorski, S R

    1994-06-01

    The effects of aluminium (as Al3+) on carbachol-induced inositol 1,4,5-trisphosphate (InsP3) production and Ca2+ mobilisation were assessed in electropermeabilised human SH-SY5Y neuroblastoma cells. Al3+ had no effect on InsP3-induced Ca2+ release but appreciably reduced carbachol-induced Ca2+ release (IC50 of approximately 90 microM). Al3+ also inhibited InsP3 production (IC50 of approximately 15 microM). Dimethyl hydroxypyridin-4-one, a potent Al3+ chelator (Ks = 31), at 100 microM was able to abort and reverse the effects of Al3+ on both Ca2+ release and InsP3 production. These data suggest that, in permeabilised cells, the effect of Al3+ on the phosphoinositide-mediated signalling pathway is at the level of phosphatidylinositol 4,5-bisphosphate hydrolysis. This may reflect interference with receptor-G protein-phospholipase C coupling or an interaction with phosphatidylinositol 4,5-bisphosphate. PMID:8189229

  2. Minocycline protects SH-SY5Y cells from 6-hydroxydopamine by inhibiting both caspase-dependent and -independent programmed cell death.

    PubMed

    Ossola, Bernardino; Lantto, Tiina A; Puttonen, Katja A; Tuominen, Raimo K; Raasmaja, Atso; Männistö, Pekka T

    2012-03-01

    Minocycline, a tetracyclic antibiotic, exerts both antiinflammation by acting on microglia and a direct protection on neurons by inhibiting the apoptotic machinery at various levels. However, we are not aware of any study investigating the effects of minocycline on caspase-independent programmed cell death (PCD) pathways. This study investigated these alternative pathways in SH-SY5Y cells, a human dopaminergic cell line, challenged with 6-hydroxydopamine (6-OHDA). Minocycline exhibited neuroprotection and inhibition of the toxin-induced caspase-3-like activity, DNA fragmentation, and chromatin condensation, hallmarks of apoptosis. Moreover, we revealed that 6-OHDA also activated caspase-independent PCDs (such as paraptosis), which required de novo protein synthesis. Additionally, by separately monitoring caspase-dependent and caspase-independent pathways, we showed that inhibition of apoptosis only partially explained the protective effect of minocycline. Moreover, we observed that minocycline reduced the protein content of cells but, unexpectedly, increased the protein synthesis. These findings suggest that minocycline may actually increase protein degradation, so it may also accelerate the clearance of aberrant proteins. In conclusion, we report for the first time evidence indicating that minocycline may inhibit PCD pathways that are additional to conventional apoptosis. PMID:22108958

  3. Reference genes identified in SH-SY5Y cells using custom-made gene arrays with validation by quantitative polymerase chain reaction.

    PubMed

    Hoerndli, Frédéric J; Toigo, Marco; Schild, Andreas; Götz, Jürgen; Day, Philip J

    2004-12-01

    Transcriptomic methods are widely used as an initial approach to gain a mechanistic insight into physiological and pathological processes. Because differences in gene regulation to be assessed by RNA screening methods (e.g., SAGE, Affymetrix GeneChips) can be very subtle, these techniques require stable reference genes for accurate normalization. It is widely known that housekeeping genes, which are routinely used for normalization, can vary significantly depending on the tissue, and experimental test. In this study, we aimed at identifying stable reference genes for a fibrillar Abeta(42) peptide-treated, human tau-expressing SH-SY5Y neuroblastoma cell line derived to model aspects of Alzheimer's disease in tissue culture. We selected genes exhibiting potential normalization characteristics from public databases to create a custom-made microarray allowing the identification of reference genes for low, intermediate, and abundant mRNAs. A subset of these candidates was subjected to quantitative real-time polymerase chain reaction and was analyzed with geNorm software. By doing so, we were able to identify GAPD, M-RIP, and POLR2F as stable and usable reference genes irrespective of differentiation status and Abeta(42) treatment. PMID:15519568

  4. Differences between normal and alpha-synuclein overexpressing SH-SY5Y neuroblastoma cells after Abeta(1-42) and NAC treatment.

    PubMed

    Hunya, Akos; Földi, István; Szegedi, Viktor; Soós, Katalin; Zarándi, Márta; Szabó, Antal; Zádori, Dénes; Penke, Botond; Datki, Zsolt L

    2008-03-28

    Alpha-synuclein (alphaSN) plays a major role in numerous neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Intracellular inclusions containing aggregated alphaSN have been reported in Alzheimer's and Parkinson's affected brains. Moreover, a proteolytic fragment of alphaSN, the so-called non-amyloid component of Alzheimer's disease amyloid (NAC) was found to be an integral part of Alzheimer's dementia related plaques. Despite the extensive research on this topic, the exact toxic mechanism of alphaSN remains elusive. We have taken the advantage of an alphaSN overexpressing SH-SY5Y cell line and investigated the effects of classical apoptotic factors (e.g. H(2)O(2), amphotericin B and ruthenium red) and aggregated disease-related peptides on cell viability compared to wild type neuroblastoma cells. It was found that alphaSN overexpressing cells are more sensitive to aggregated peptides treatment than normal expressing counterparts. In contrast, cells containing elevated amount of alphaSN were less vulnerable to classical apoptotic stressors than wild type cells. In addition, alphaSN overexpression is accompanied by altered phenotype, attenuated proliferation kinetics, increased neurite arborisation and decreased cell motility. Based on these results, the alphaSN overexpressing cell lines may represent a good and effective in vitro model for Alzheimer's and Parkinson's disease. PMID:18355641

  5. Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells

    PubMed Central

    Janhom, Prachya; Dharmasaroja, Permphan

    2015-01-01

    In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+ on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+ treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation. PMID:26357513

  6. Neuroprotective Effects of Alpha-Mangostin on MPP(+)-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells.

    PubMed

    Janhom, Prachya; Dharmasaroja, Permphan

    2015-01-01

    In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP(+)-induced apoptosis. The effects of alpha-mangostin on MPP(+)-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP(+) on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP(+). Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP(+). The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation. PMID:26357513

  7. Cellular Stress and p53-Associated Apoptosis by Juniperus communis L. Berry Extract Treatment in the Human SH-SY5Y Neuroblastoma Cells.

    PubMed

    Lantto, Tiina A; Laakso, Into; Dorman, H J Damien; Mauriala, Timo; Hiltunen, Raimo; Kõks, Sulev; Raasmaja, Atso

    2016-01-01

    Plant phenolics have shown to activate apoptotic cell death in different tumourigenic cell lines. In this study, we evaluated the effects of juniper berry extract (Juniperus communis L.) on p53 protein, gene expression and DNA fragmentation in human neuroblastoma SH-SY5Y cells. In addition, we analyzed the phenolic composition of the extract. We found that juniper berry extract activated cellular relocalization of p53 and DNA fragmentation-dependent cell death. Differentially expressed genes between treated and non-treated cells were evaluated with the cDNA-RDA (representational difference analysis) method at the early time point of apoptotic process when p53 started to be activated and no caspase activity was detected. Twenty one overexpressed genes related to cellular stress, protein synthesis, cell survival and death were detected. Interestingly, they included endoplasmic reticulum (ER) stress inducer and sensor HSPA5 and other ER stress-related genes CALM2 and YKT6 indicating that ER stress response was involved in juniper berry extract mediated cell death. In composition analysis, we identified and quantified low concentrations of fifteen phenolic compounds. The main groups of them were flavones, flavonols, phenolic acids, flavanol and biflavonoid including glycosides of quercetin, apigenin, isoscutellarein and hypolaetin. It is suggested that juniper berry extract induced the p53-associated apoptosis through the potentiation and synergism by several phenolic compounds. PMID:27420050

  8. Agmatine Protects Against 6-OHDA-Induced Apoptosis, and ERK and Akt/GSK Disruption in SH-SY5Y Cells.

    PubMed

    Amiri, Esmat; Ghasemi, Rasoul; Moosavi, Maryam

    2016-08-01

    6-Hydroxydopamine (6-OHDA), a metabolite of dopamine is known to induce dopaminergic cell toxicity which makes that a suitable agent inducing an experimental model of Parkinson's disease (PD). Agmatine has been shown to protect against some cellular and animal PD models. This study was aimed to assess whether agmatine prevents 6-OHDA-induced SH-SY5Y cell death and if yes, then how it affects Akt/glycogen synthesis kinase-3β (GSK-3β) and extracellular signal-regulated kinases (ERK) signals. The cells were treated with different drugs, and their viability was examined via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and morphological observation. Western blot studies were done to assess cleaved caspase-3, Akt/GSK-3β, and ERK proteins. 6-OHDA-induced cell death and caspase-3 cleavage, while agmatine prevented those changes. 6-OHDA also decreased the amount of phosphorylated Akt (pAkt)/Akt while increased GSK-3β activity which was prevented by agmatine. Additionally, this toxin increased pERK/ERK ratio which was averted again by agmatine. The PI3/Akt inhibitor, LY294002, impeded the changes induced by agmatine, while ERK inhibitor (PD98059) did not disturb the effects of agmatine, and by itself, it preserved the cells against 6-OHDA toxicity. This study revealed that agmatine is protective in 6-OHDA model of PD and affects Akt/GSK-3β and ERK pathways. PMID:26346882

  9. Structural and waveguiding characteristics of Er3+:Yb3Al5-yGayO12 films grown by the liquid phase epitaxy

    NASA Astrophysics Data System (ADS)

    Hlásek, T.; Rubešová, K.; Jakeš, V.; Nekvindová, P.; Kučera, M.; Daniš, S.; Veis, M.; Havránek, V.

    2015-11-01

    Erbium (Er3+) doped ytterbium garnet (Er:Yb3Al5-yGayO12; y = 0, 0.55 and 1.1) single crystalline thick films have been grown by the low-temperature liquid phase epitaxy method (LPE). The composition of the films was determined using the high resolution XRD, the particle-induced X-ray emission spectroscopy (PIXE) and the particle-induced gamma-ray emission spectroscopy (PIGE). The lattice mismatch between films and substrates was investigated by the high-resolution X-ray diffraction. The surface analysis was carried out by the atomic force microscopy (AFM). Pure infrared emission of Er3+ ions was observed in all films containing gallium. The characteristics such as refractive index, thickness and light propagation were studied by the m-line spectroscopy (MLS) using several wavelengths (633, 964, 1311 and 1552 nm). All samples, where y = 1.1, were multimode waveguides. For these reasons, the Er:Yb3Al3.9Ga1.1O12 seems to be a promising material for light amplifiers in the IR region.

  10. Some Commonly Used Brominated Flame Retardants Cause Ca2+-ATPase Inhibition, Beta-Amyloid Peptide Release and Apoptosis in SH-SY5Y Neuronal Cells

    PubMed Central

    Al-Mousa, Fawaz; Michelangeli, Francesco

    2012-01-01

    Brominated flame retardants (BFRs) are chemicals commonly used to reduce the flammability of consumer products and are considered pollutants since they have become widely dispersed throughout the environment and have also been shown to bio-accumulate within animals and man. This study investigated the cytotoxicity of some of the most commonly used groups of BFRs on SH-SY5Y human neuroblastoma cells. The results showed that of the BFRs tested, hexabromocyclododecane (HBCD), tetrabromobisphenol-A (TBBPA) and decabromodiphenyl ether (DBPE), all are cytotoxic at low micromolar concentrations (LC50 being 2.7±0.7µM, 15±4µM and 28±7µM, respectively). They induced cell death, at least in part, by apoptosis through activation of caspases. They also increased intracellular [Ca2+] levels and reactive-oxygen-species within these neuronal cells. Furthermore, these BFRs also caused rapid depolarization of the mitochondria and cytochrome c release in these neuronal cells. Elevated intracellular [Ca2+] levels appear to occur through a mechanism involving microsomal Ca2+-ATPase inhibition and this maybe responsible for Ca2+-induced mitochondrial dysfunction. In addition, µM levels of these BFRs caused β-amyloid peptide (Aβ-42) processing and release from these cells with a few hours of exposure. These results therefore shows that these pollutants are both neurotoxic and amyloidogenic in-vitro. PMID:22485137

  11. Lycopene protects human SH-SY5Y neuroblastoma cells against hydrogen peroxide-induced death via inhibition of oxidative stress and mitochondria-associated apoptotic pathways

    PubMed Central

    FENG, CHUNSHENG; LUO, TIANFEI; ZHANG, SHUYAN; LIU, KAI; ZHANG, YANHONG; LUO, YINAN; GE, PENGFEI

    2016-01-01

    Oxidative stress, which is characterized by excessive production of reactive oxygen species (ROS), is a common pathway that results in neuronal injury or death due to various types of pathological stress. Although lycopene has been identified as a potent antioxidant, its effect on hydrogen peroxide (H2O2)-induced neuronal damage remains unclear. In the present study, pretreatment with lycopene was observed to protect SH-SY5Y neuroblastoma cells against H2O2-induced death via inhibition of apoptosis resulting from activation of caspase-3 and translocation of apoptosis inducing factor (AIF) to the nucleus. Furthermore, the over-produced ROS, as well as the reduced activities of anti-oxidative enzymes, superoxide dismutase and catalase, were demonstrated to be alleviated by lycopene. Additionally, lycopene counteracted H2O2-induced mitochondrial dysfunction, which was evidenced by suppression of mitochondrial permeability transition pore opening, attenuation of the decline of the mitochondrial membrane potential, and inhibition of the increase of Bax and decrease of Bcl-2 levels within the mitochondria. The release of cytochrome c and AIF from the mitochondria was also reduced. These results indicate that lycopene is a potent neuroprotectant against apoptosis, oxidative stress and mitochondrial dysfunction, and could be administered to prevent neuronal injury or death. PMID:27035331

  12. PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium

    SciTech Connect

    Zhu Xuhui; Yao Honghong; Peng Fuwang; Callen, Shannon; Buch, Shilpa

    2009-10-15

    The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process. Furthermore, we also found that pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity by decreasing extracellular glutamate levels. We also demonstrated that extracellular calcium chelator EGTA was able to abolish PDGF-mediated neuroprotection, thereby underscoring the role of calcium signaling in PDGF-mediated neuroprotection. We also showed that Erk signaling pathway was critical for PDGF-mediated protection of cells. Additionally, blocking calcium entry with EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in the protection of cells against HIV Tat toxicity.

  13. Autism Spectrum Disorders: Sex Differences in Autistic Behaviour Domains and Coexisting Psychopathology

    ERIC Educational Resources Information Center

    Holtmann, Martin; Bolte, Sven; Poustka, Fritz

    2007-01-01

    The purpose of the present study was to examine possible differences between high-functioning males and females with autism spectrum disorder (ASD) regarding the core symptoms of autism and coexisting psychopathology. A total of 23 females and 23 males matched for age, IQ, and ASD diagnoses were recruited(mean age 11y 9mo [SD 4y 5mo], range 5y-20y…

  14. Cognitive Profile in Young Icelandic Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Sigurdardottir, Solveig; Eiriksdottir, Audur; Gunnarsdottir, Eva; Meintema, Marrit; Arnadottir, Unnur; Vik, Torstein

    2008-01-01

    We describe the cognitive profile in a complete national cohort of children with cerebral palsy (CP). One hundred and twenty-seven Icelandic children (67 females, 60 males) with CP, born between 1985 and 2000 and assessed between the ages of 4 and 6 years 6 months (mean age 5y 5mo, SD 6mo), were included in the study. IQ was measured using the…

  15. Combinatorial topology of uranyl molybdate sheets: syntheses and crystal structures of (C 6H 14N 2) 3[(UO 2) 5(MoO 4) 8](H 2O) 4 and (C 2H 10N 2)[(UO 2)(MoO 4) 2

    NASA Astrophysics Data System (ADS)

    Krivovichev, Sergey V.; Burns, Peter C.

    2003-01-01

    Two new mixed organic-inorganic uranyl molybdates, (C 6H 14N 2) 3[(UO 2) 5(MoO 4) 8](H 2O) 4 ( 1) and (C 2H 10N 2)[(UO 2)(MoO 4) 2] ( 2), have been obtained by hydrothermal methods. The structure of 1 [triclinic, P 1¯, Z=1, a=11.8557(9), b=11.8702(9), c=12.6746(9) Å, α=96.734(2)°, β=91.107(2)°, γ=110.193(2)°, V=1659.1(2) Å] has been solved by direct methods and refined on the basis of F2 for all unique reflections to R1=0.058, which was calculated for the 5642 unique observed reflections (| Fo|⩾4 σF). The structure contains topologically novel sheets of uranyl square bipyramids, uranyl pentagonal bipyramids, and MoO 4 tetrahedra, with composition [(UO 2) 5(MoO 4) 8] 6-, that are parallel to (-101). H 2O groups and 1,4-diazabicyclo [2.2.2]-octane (DABCO) molecules are located in the interlayer, where they provide linkage of the sheets. The structure of 2 [triclinic, P 1¯, Z=2, a=8.4004(4), b=11.2600(5), c=13.1239(6) Å, α=86.112(1)°, β=86.434(1)°, γ=76.544(1)°, V=1203.14(10) Å] has been solved by direct methods and refined on the basis of F2 for all unique reflections to R1=0.043, which was calculated for 5491 unique observed reflections (| Fo|⩾4 σF). The structure contains topologically novel sheets of uranyl pentagonal bipyramids and MoO 4 tetrahedra, with composition [(UO 2)(MoO 4) 2] 2-, that are parallel to (110). Ethylenediamine molecules are located in the interlayer, where they provide linkage of the sheets. All known topologies of uranyl molybdate sheets of corner-sharing U and Mo polyhedra can be described by their nodal representations (representations as graphs in which U and Mo polyhedra are given as black and white vertices, respectively). Each topology can be derived from a simple black-and-white graph of six-connected black vertices and three-connected white vertices by deleting some of its segments and white vertices.

  16. Myosin heavy chain composition in the rat diaphragm - Effect of age and exercise training

    NASA Technical Reports Server (NTRS)

    Gosselin, Luc E.; Betlach, Michael; Vailas, Arthur C.; Greaser, Marion L.; Thomas, D. P.

    1992-01-01

    The effects of aging and exercise training on the myosin heavy chain (MHC) composition were determined in both the costal and crural diaphragm regions of female Fischer 344 rats. Treadmill running at 75 percent maximal oxygen consumption resulted in similar increases in plantaris muscle citrate synthase activity in both young (5 mo) and old (23mo) trained animals (P less than 0.05). It was found that the ratio of fast to slow MHC was significantly higher (P less than 0.005) in the crural compared with costal diaphragm region in both age groups. A significant age-related increase in persentage of slow MHC was observed in both diaphragm regions. The relative proportion of slow MHC in either costal or crural region was not changed by exercise training.

  17. Skin Aging

    MedlinePlus

    ... too. Sunlight is a major cause of skin aging. You can protect yourself by staying out of ... person has smoked. Many products claim to revitalize aging skin or reduce wrinkles, but the Food and ...

  18. Astroglial U87 Cells Protect Neuronal SH-SY5Y Cells from Indirect Effect of Radiation by Reducing DNA Damage and Inhibiting Fas Mediated Apoptotic Pathway in Coculture System.

    PubMed

    Saeed, Yasmeen; Rehman, Abdul; Xie, Bingjie; Xu, Jin; Hong, Ma; Hong, Qing; Deng, Yulin

    2015-08-01

    Recent studies provide the evidence that indirect effects of radiation could lead to neuronal cells death but underlying mechanism is not completely understood. On the other hand astroglial cells are known to protect neuronal cells against stress conditions in vivo and invitro. Yet, the fate of neuronal cells and the neuroprotective effect of coculture system (with glial cells) in response to indirect radiation exposure remain rarely discussed. Here, we purpose that the indirect effect of radiation may induce DNA damage by cell cycle arrest and receptor mediated apoptotic cascade which lead to apoptotic death of neuronal SH-SY5Y cells. We also hypothesized that coculture (with glial U87) may relieved the neuronal SH-SY5Y cells from toxicity of indirect effects radiation by reducing DNA damage and expression of apoptotic proteins in vitro. In the present study irradiated cell conditioned medium (ICCM) was used as source of indirect effect of radiation. Neuronal SH-SY5Y cells were exposed to ICCM with and without coculture with (glial U87) in transwell coculture system respectively. Various endpoints such as, cell survival number assay, Annexin V/PI assay, cell cycle analysis by flow cytometer, mRNA level of Fas receptor by q RT-PCR, expression of key apoptotic proteins by western blot and estimation of neurotrophic factors by ELISA method were analyzed into neuronal SH-SY5Y cells with and without co culture after ICCM exposure respectively. We found that ICCM induced DNA damage in neuronal SH-SY5Y cells by significant increase in cell cycle arrest at S-phase (***P < 0.001) which was further supported by over expression of P53 protein (**P < 0.01). While coculture (with glial U87), significantly reduced the ICCM induced cell cycle arrest and expression of P53 ((###) P < 0.001) neuronal SH-SY5Y cells. Further investigation of the underlying apoptotic mechanism revealed that in coculture system; ICCM induced elevated level of FAS mRNA level was significantly reduced

  19. Communication & Aging.

    ERIC Educational Resources Information Center

    Arnold, William E.

    This extensive bibliography contains more than 1,800 entries about communication and aging. The citations include journal articles, unpublished papers, speeches, dissertations, research studies, and books that relate aging and the aged to a variety of topics, including the following: physiological deterioration, socialization, political…

  20. Skin Aging

    MedlinePlus

    Your skin changes as you age. You might notice wrinkles, age spots and dryness. Your skin also becomes thinner and loses fat, making it ... heal, too. Sunlight is a major cause of skin aging. You can protect yourself by staying out ...

  1. Creative Aging.

    ERIC Educational Resources Information Center

    Ager, Charlene Lee; And Others

    1981-01-01

    Explores some divergent attitudes toward aging, negative as well as positive. Presents a neurophysiological framework to support the belief that aging is an active and creative process. Explores physical, psychological, and sociological aspects, and identifies three factors in the creative aging process. (Author/JAC)

  2. Crystal structure and microwave dielectric behaviors of ultra-low-temperature fired x(Ag(0.5)Bi(0.5))MoO₄-(1 - x)BiVO₄ (0.0 ≤ x ≤ 1.0) solid solution with scheelite structure.

    PubMed

    Zhou, Di; Pang, Li-Xia; Qi, Ze-Ming

    2014-09-01

    x(Ag(0.5)Bi(0.5))MoO4-(1 - x)BiVO4 (0.0 ≤ x ≤ 1.0) ceramics were prepared by using the solid-state reaction technique. Ceramics with x < 0.10 had a monoclinic scheelite structure, while those with ≥0.10 were tetragonal scheelite solid solutions. This indicates that the phase transformation temperature of BiVO4 was lowered through the formation of a solid solution. The thermal expansion data of the x = 0.08 sample showed that the thermal expansion coefficient was increased suddenly from +8 to +15 ppm/°C at about 60.6 °C due to the phase transition. Similarly, a maximum value of microwave dielectric permittivity was revealed at about 65 °C for the x = 0.08 sample. All of the ceramics could be well sintered below 700 °C. Good microwave dielectric behaviors, with relative permittivity >75 and Q(f) > 9000 GHz, were obtained in ceramics with compositions near x = 0.10. Both the THz data and the infrared spectra were used to study the intrinsic dielectric behavior of the materials at microwave frequencies. PMID:25105210

  3. SCC of austenitic stainless steel, Ni-21Cr-13.5Mo alloy, and 0.3Mo-0.8Ni-Ti in 350 C synthetic, NO{sub 2}2-NO{sub 3}-OH tank waste

    SciTech Connect

    Pednekar, S.P.

    1998-12-31

    A necessary step in preparation of high-level radioactive tank waste for sate disposal is removal of non radioactive organic and inorganic components from washed waste. The oxidizing and alkaline nature of most wastes allows the removal of the organic components as water vapor, carbon dioxide, and ammonia gas merely by heating the wastes to no more than 350 C. Type 3 16L stainless steel (UNS S3 1603) a 21Cr-13.5Mo-Ni alloy (UNS N06022), and 0.8Ni-0.3Mo-Ti alloy (UNS R53400) were candidate materials for reactors in which the oxidation could be performed. Slow-strain-rate tests were performed on these three materials at a strain rate of 10{sup {minus}6}sec{sup {minus}1} in a diluted waste type solution containing 4.1% NO{sub 2}, 3.7% NO{sub 3}, 1% OH, and 0.22% TIC. All three materials showed intergranular stress corrosion cracking with substantial losses in ductility and strength.

  4. Syngas production on a symmetrical solid oxide H2O/CO2 co-electrolysis cell with Sr2Fe1.5Mo0.5O6-Sm0.2Ce0.8O1.9 electrodes

    NASA Astrophysics Data System (ADS)

    Wang, Yao; Liu, Tong; Fang, Shumin; Chen, Fanglin

    2016-02-01

    High temperature H2O/CO2 co-electrolysis process is performed on the symmetrical Sr2Fe1.5Mo0.5O6(SFM)-Sm0.2Ce0.8O1.9(SDC)/La0.8Sr0.2Ga0.87Mg0.13O3 (LSGM)/SFM-SDC cells, which exhibit excellent electrochemical performance with the current density of -734 mAcm-2 at 1.3 V and the interfacial polarization resistance of 0.48 Ωcm2 at 850 °C. Enhanced co-electrolysis kinetics are obtained with increasing the operating temperature and applied cell voltage. Synthesis gas of H2 and CO is produced by H2O splitting and reverse water gas shift (RWGS) reaction on the SFM-SDC/LSGM/SFM-SDC co-electrolysis cells. Effects of temperature and electrolysis current on the produced gas fraction are predicted using the chemical equilibrium co-electrolysis model. High CO2 conversion rate and ideal H2 to CO ratio of approximately 2 can be achieved by adjusting appropriate inlet gas fraction, temperature and electrolysis current. The SFM-SDC/LSGM/SFM-SDC cell shows a relative stable cell voltage in the 103-h galvanostatic test.

  5. Single layer fuel cell based on a composite of Ce0.8Sm0.2O2-δ-Na2CO3 and a mixed ionic and electronic conductor Sr2Fe1.5Mo0.5O6-δ

    NASA Astrophysics Data System (ADS)

    Dong, Xiao; Tian, Li; Li, Jiang; Zhao, Yicheng; Tian, Ye; Li, Yongdan

    2014-03-01

    A new kind of single layer fuel cell (SLFC) based on a composite material of Ce0.8Sm0.2O2-δ (SDC)-Na2CO3 and Sr2Fe1.5Mo0.5O6-δ (SFM) is successfully fabricated and characterized. As a mixed ionic and electronic conductor, SFM provides more reaction areas than the triple phase boundary provided by a simple mixture of ionic conductor and electronic conductor. SDC-Na2CO3 is used to adjust the ratio of ionic and electronic conductivities. The influence of the SFM content on the electrochemical performance of the SLFC is examined. The pellet made of 30 wt.% SFM and 70 wt.% SDC-Na2CO3 exhibits the highest open circuit voltage of 1.05 V and output of 360 mW cm-2 at 750 °C. Besides, by discussing influence factors of the OCV of the cell, the reason why the SLFC can give a similar OCV and output comparing with the conventional three-layer fuel cell, has been explained in detail.

  6. The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells.

    PubMed

    La Marca, Valeria; Spagnuolo, Maria Stefania; Cigliano, Luisa; Marasco, Daniela; Abrescia, Paolo

    2014-07-01

    Cholesterol is mostly removed from the CNS by its conversion to cerebrosterol (24(S)-hydroxycholesterol, 24(S)OH-C), which is transported to the circulation for bile formation in liver. A neurotoxic role of this oxysterol was previously demonstrated in cell culture. Here, we provide evidence that the enzyme lecithin-cholesterol acyltransferase, long known to esterify cholesterol, also produces monoesters of 24(S)OH-C. Proteoliposomes containing apolipoprotein A-I or apolipoprotein E were used to stimulate the enzyme activity and entrap the formed esters. Proteoliposomes with apolipoprotein A-I were found to be more active than those with apolipoprotein E in stimulating the production of oxysteryl esters. Cholesterol and 24(S)OH-C were found to compete for enzyme activity. High levels of haptoglobin, as those circulating during the acute inflammatory phase, inhibited 24(S)OH-C esterification. When highly neurotoxic 24(S)OH-C was treated with enzyme and proteoliposomes before incubation with differentiated SH-SY5Y cells, the neuron survival improved. The esters of 24(S)OH-C, embedded into proteoliposomes by the enzyme and isolated from unesterified 24(S)OH-C by gel filtration chromatography, did not enter the neurons in culture. These results suggest that the enzyme, in the presence of the apolipoproteins, converts 24(S)OH-C into esters restricted to the extracellular environment, thus preventing or limiting oxysterol-induced neurotoxic injuries to neurons in culture. 24-hydroxycholesterol (24(S)OH-C) is neurotoxic. The enzyme lecithin-cholesterol acyltransferase (LCAT) synthesizes monoesters of 24(S)OH-C in reaction mixtures with proteoliposomes containing phospholipids and apolipoprotein A-I or apolipoprotein E. The esters, also produced by incubation of cerebrospinal fluid only with tritiated 24(S)OH-C, are embedded into lipoproteins that do not enter neurons in culture. The enzyme activity limits the toxicity of 24-hydroxycholesterol in neuron culture. PMID

  7. Genistein Inhibits Aβ25-35-Induced Synaptic Toxicity and Regulates CaMKII/CREB Pathway in SH-SY5Y Cells.

    PubMed

    Xi, Yuan-Di; Zhang, Dan-Di; Ding, Juan; Yu, Huan-Ling; Yuan, Lin-Hong; Ma, Wei-Wei; Han, Jing; Xiao, Rong

    2016-10-01

    Genistein (Gen), as a functional food in human diet, has shown many beneficial effects on neurodegenerative diseases such as Alzheimer's disease (AD). But the neuroprotective mechanism of Gen is not clear. Because synaptic failure is considered as the earliest phase in the pathogenesis of AD, we try to validate our hypothesis that synapse may be one target of Gen on protecting neurons. In this study, SH-SY5Y cells were pre-incubated with or without Gen for 2 h followed by the incubation with Aβ25-35 (25 μmol/L) for another 24 h. Flow cytometry, Western Blots, and RT-PCR analysis were used to test the synaptic factors. The data showed that Gen pre-treatment could reverse the Aβ25-35-induced down-regulation of synaptophysin and postsynaptic marker postsynaptic density-95. In addition, the down-regulation of NR1 and NR2B induced by Aβ25-35 which are subunits of N-methyl-D-aspartate receptor also could be antagonized by pre-treatment of Gen. Moreover, the factors of CaMKII/CREB signaling pathway were detected. The results showed that mRNA and protein expressions of (Ca(2+))/calmodulin(CaM), CaMKII/pCaMKII, and CREB/pCREB were significantly down-regulated by Aβ25-35, but they were all restored by the pre-treatment of Gen. Furthermore, Gen also maintained the intracellular Ca(2+) concentration which was disturbed by Aβ25-35. In conclusion, these results suggested that Gen could protect synaptic dysfunction induced by Aβ, and the mechanism might be associated with the regulation of synaptic markers and Ca(2+) level through activating CaM/CaMK/CREB signaling pathway. PMID:26658733

  8. Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

    PubMed Central

    Dodson, Matthew; Liang, Qiuli; Johnson, Michelle S; Redmann, Matthew; Fineberg, Naomi; Darley-Usmar, Victor M; Zhang, Jianhua

    2013-01-01

    How cellular metabolic activities regulate autophagy and determine the susceptibility to oxidative stress and ultimately cell death in neuronal cells is not well understood. An important example of oxidative stress is 4-hydroxynonenal (HNE), which is a lipid peroxidation product that is formed during oxidative stress, and accumulates in neurodegenerative diseases causing damage. The accumulation of toxic oxidation products such as HNE, is a prevalent feature of neurodegenerative diseases, and can promote organelle and protein damage leading to induction of autophagy. In this study, we used differentiated SH-SY5Y neuroblastoma cells to investigate the mechanisms and regulation of cellular susceptibility to HNE toxicity and the relationship to cellular metabolism. We found that autophagy is immediately stimulated by HNE at a sublethal concentration. Within the same time frame, HNE induces concentration dependent CASP3/caspase 3 activation and cell death. Interestingly, both basal and HNE-activated autophagy, were regulated by glucose metabolism. Inhibition of glucose metabolism by 2-deoxyglucose (2DG), at a concentration that inhibited autophagic flux, further exacerbated CASP3 activation and cell death in response to HNE. Cell death was attenuated by the pan-caspase inhibitor Z-VAD-FMK. Specific inhibition of glycolysis using koningic acid, a GAPDH inhibitor, inhibited autophagic flux and exacerbated HNE-induced cell death similarly to 2DG. The effects of 2DG on autophagy and HNE-induced cell death could not be reversed by addition of mannose, suggesting an ER stress-independent mechanism. 2DG decreased LAMP1 and increased BCL2 levels suggesting that its effects on autophagy may be mediated by more than one mechanism. Furthermore, 2DG decreased cellular ATP, and 2DG and HNE combined treatment decreased mitochondrial membrane potential. We conclude that glucose-dependent autophagy serves as a protective mechanism in response to HNE. PMID:24145463

  9. Melatonin regulates the transcription of βAPP-cleaving secretases mediated through melatonin receptors in human neuroblastoma SH-SY5Y cells.

    PubMed

    Panmanee, Jiraporn; Nopparat, Chutikorn; Chavanich, Napapit; Shukla, Mayuri; Mukda, Sujira; Song, Weihong; Vincent, Bruno; Govitrapong, Piyarat

    2015-10-01

    Melatonin is involved in the control of various physiological functions, such as sleep, cell growth and free radical scavenging. The ability of melatonin to behave as an antioxidant, together with the fact that the Alzheimer-related amyloid β-peptide (Aβ) triggers oxidative stress through hydroxyl radical-induced cell death, suggests that melatonin could reduce Alzheimer's pathology. Although the exact etiology of Alzheimer's disease (AD) remains to be established, excess Aβ is believed to be the primary contributor to the dysfunction and degeneration of neurons that occurs in AD. Aβ peptides are produced via the sequential cleavage of β-secretase β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase (PS1/PS2), while α-secretase (ADAM10) prevents the production of Aβ peptides. We hypothesized that melatonin could inhibit BACE1 and PS1/PS2 and enhance ADAM10 expression. Using the human neuronal SH-SY5Y cell line, we found that melatonin inhibited BACE1 and PS1 and activated ADAM10 mRNA level and protein expression in a concentration-dependent manner and mediated via melatonin G protein-coupled receptors. Melatonin inhibits BACE1 and PS1 protein expressions through the attenuation of nuclear factor-κB phosphorylation (pNF-κB). Moreover, melatonin reduced BACE1 promoter transactivation and consequently downregulated β-secretase catalytic activity. The present data show that melatonin is not only a potential regulator of β/γ-secretase but also an activator of α-secretase expression through the activation of protein kinase C, thereby favoring the nonamyloidogenic pathway over the amyloidogenic pathway. Altogether, our findings suggest that melatonin may be a potential therapeutic agent for reducing the risk of AD in humans. PMID:26123100

  10. Mu-opioid receptor activation prevents apoptosis following serum withdrawal in differentiated SH-SY5Y cells and cortical neurons via phosphatidylinositol 3-kinase.

    PubMed

    Iglesias, M; Segura, M F; Comella, J X; Olmos, G

    2003-03-01

    Opioid peptides and alkaloids exert their effects via G protein-coupled receptors (GPCRs). It has been shown that, in addition to trophic factors, some GPCRs are able to activate the phosphatidylinositol 3-kinase/Akt (PI 3-K/Akt) signal transduction pathway, thus leading to cell survival. The aim of this study was to test whether activation of mu-opioid receptors has protective effects on serum withdrawal-induced cell death and to study the possible implication of PI 3-K in this process. In SH-SY5Y neuroblastoma cells fully differentiated by exposure to retinoic acid for five days, the enkephalin derivative selective mu-agonist DAMGO (0.1-2 microM) and the alkaloid morphine (0.1-10 microM) promoted cell survival after serum deprivation (MTT and trypan blue exclusion assays), without inducing cell proliferation. These effects were fully reversed by naloxone, by the selective mu-antagonist beta-funaltrexamine (beta-FNA) and also by the specific PI 3-K inhibitor LY294002. The two agonists stimulated Akt phosphorylation and the effect was also abolished by beta-FNA and by LY294002. In mouse primary cortical neurons, DAMGO reduced the percentage of apoptosis after 6, 12, 24 and 48 h of serum withdrawal; as determined by Hoechst staining. This effect was blocked by beta-FNA, by pre-treatment with pertussis toxin and by LY294002. DAMGO also stimulated Akt phosphorylation via PI 3-K in this primary neuronal culture. Together, these results indicate that stimulation of the mu-opioid receptor promotes neuronal survival in a G(i/o)-linked, PI 3-K-dependent signaling cascade and suggest that Akt may be a key downstream kinase involved in this anti-apoptotic effect. PMID:12646285

  11. Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens

    PubMed Central

    2014-01-01

    Background Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract. Methods Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions. Results Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10-9 M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range. Conclusions The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation. PMID:24642002

  12. Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

    PubMed Central

    Zeidán-Chuliá, Fares; Kolling, Eduardo Antônio; Rybarczyk-Filho, José Luiz; Ambrosi, Priscilla; Resende Terra, Silvia; Pires, André Simões; da Rocha, João Batista Teixeira; Antônio Behr, Guilherme; Fonseca Moreira, José Cláudio

    2013-01-01

    Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL), taurine (1–16 mg/mL), and guarana (3.125–50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”), could be a cause of in vitro toxicity induced by these drugs. PMID:23766861

  13. Lithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cells

    PubMed Central

    Alural, Begum; Ozerdem, Aysegul; Allmer, Jens; Genc, Kursad; Genc, Sermin

    2015-01-01

    Lithium is a mood stabilizing agent commonly used for the treatment of bipolar disorder. Here, we investigated the potential neuroprotective effect of lithium against paraquat toxicity and its underlying mechanisms in vitro. SH-SY5Y human neuroblastoma cells were treated with paraquat (PQ) 0.5 mM concentration after lithium pretreatment to test lithium's capability in preventing cell toxicity. Cell death was evaluated by LDH, WST-8, and tryphan blue assays. Apoptosis was analyzed using DNA fragmentation, Annexin V immunostaining, Sub G1 cell cycle analysis, and caspase-3 activity assays. BCL2, BAX, and NRF2 protein expression were evaluated by Western-blotting and the BDNF protein level was determined with ELISA. mRNA levels of BCL2, BAX, BDNF, and NRF2 target genes (HO-1, GCS, NQO1), as well as miR-34a expression were analyzed by qPCR assay. Functional experiments were done via transfection with NRF2 siRNA and miR-34a mimic. Lithium treatment prevented paraquat induced cell death and apoptosis. Lithium treated cells showed increased anti-apoptotic protein BCL2 and decreased pro-apoptotic protein BAX expression. Lithium exerted a neurotrophic effect by increasing BDNF protein expression. It also diminished reactive oxygen species production and activated the redox sensitive transcription factor NRF2 and increased its target genes expression. Knockdown of NRF2 abolished neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium. Furthermore, lithium significantly decreased both basal and PQ-induced expression of miR-34a. Transfection of miR-34a specific mimic reversed neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium against PQ-toxicity. Our results revealed two novel mechanisms of lithium neuroprotection, namely NRF2 activation and miR-34a suppression. PMID:26074776

  14. Induction of genomic instability, oxidative processes, and mitochondrial activity by 50Hz magnetic fields in human SH-SY5Y neuroblastoma cells.

    PubMed

    Luukkonen, Jukka; Liimatainen, Anu; Juutilainen, Jukka; Naarala, Jonne

    2014-02-01

    Epidemiological studies have suggested that exposure to 50Hz magnetic fields (MF) increases the risk of childhood leukemia, but there is no mechanistic explanation for carcinogenic effects. In two previous studies we have observed that a 24-h pre-exposure to MF alters cellular responses to menadione-induced DNA damage. The aim of this study was to investigate the cellular changes that must occur already during the first 24h of exposure to MF, and to explore whether the MF-induced changes in DNA damage response can lead to genomic instability in the progeny of the exposed cells. In order to answer these questions, human SH-SY5Y neuroblastoma cells were exposed to a 50-Hz, 100-μT MF for 24h, followed by 3-h exposure to menadione. The main finding was that MF exposure was associated with increased level of micronuclei, used as an indicator of induced genomic instability, at 8 and 15d after the exposures. Other delayed effects in MF-exposed cells included increased mitochondrial activity at 8d, and increased reactive oxygen species (ROS) production and lipid peroxidation at 15d after the exposures. Oxidative processes (ROS production, reduced glutathione level, and mitochondrial superoxide level) were affected by MF immediately after the exposure. In conclusion, the present results suggest that MF exposure disturbs oxidative balance immediately after the exposure, which might explain our previous findings on MF altered cellular responses to menadione-induced DNA damage. Persistently elevated levels of micronuclei were found in the progeny of MF-exposed cells, indicating induction of genomic instability. PMID:24374227

  15. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-01

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip. PMID:27444019

  16. Mosaic aging

    PubMed Central

    Walker, Lary C.; Herndon, James G.

    2010-01-01

    Summary Although all multicellular organisms undergo structural and functional deterioration with age, senescence is not a uniform process. Rather, each organism experiences a constellation of changes that reflect the heterogeneous effects of age on molecules, cells, organs and systems, an idiosyncratic pattern that we refer to as mosaic aging. Varying genetic, epigenetic and environmental factors (local and extrinsic) contribute to the aging phenotype in a given individual, and these agents influence the type and rate of functional decline, as well as the likelihood of developing age-associated afflictions such as cardiovascular disease, arthritis, cancer, and neurodegenerative disorders. Identifying key factors that drive aging, clarifying their activities in different systems, and in particular understanding how they interact will enhance our comprehension of the aging process, and could yield insights into the permissive role that senescence plays in the emergence of acute and chronic diseases of the elderly. PMID:20110150

  17. Amyloid Beta Peptides Affect Pregnenolone and Pregnenolone Sulfate Levels in PC-12 and SH-SY5Y Cells Depending on Cholesterol.

    PubMed

    Calan, Ozlem Gursoy; Akan, Pinar; Cataler, Aysenur; Dogan, Cumhur; Kocturk, Semra

    2016-07-01

    Increased amyloid beta (AB) peptide concentration is one of the initiating factors in the neurodegeneration process. It has been suggested that cholesterol induces the synthesis of AB peptide from amyloid precursor protein or facilitates the formation of amyloid plaque by lowering the aggregation threshold of the peptide. It is also shown that AB peptides may affect cholesterol metabolism and the synthesis of steroid hormones such as progesterone and estradiol. Pregnenolone (P) and pregnenolone sulfate (PS) are the major steroids produced from cholesterol in neural tissue. In toxicity conditions, the effect of AB peptides on P and PS levels has not yet been determined. Furthermore, it has not been clearly defined how changes in cellular P and PS levels affect neuronal cell survival. The aim of this study was to determine the effects of AB peptides on cellular changes in P and PS levels depending on the level of their main precursor, cholesterol. Cholesterol and toxic concentrations of AB fragments (AB 25-35, AB 1-40 and AB 1-42) were applied to PC-12 and SH-SY5Y cells. Changes in cellular cholesterol, P and PS levels were determined simultaneously in a dose-and time-dependent manner. The cell viability and cell death types were also evaluated. AB peptides affected both cell viability and P/PS levels. Steroid levels were altered depending on AB fragment type and the cholesterol content of the cells. Treatment with each of the AB fragments alone increased P levels by twofold. However, combined treatment with AB peptides and cholesterol increased P levels by approximately sixfold, while PS levels were increased only about 2.5 fold in both cell lines. P levels in the groups treated with AB 25-35 were higher than those in AB 1-40 and AB 1-42 groups. The cell viabilities were significantly low in the group treated by AB and cholesterol (9 mM). The effect of AB peptides on P levels might be a result of cellular self-defense. On the other hand, the rate of P increase

  18. Unequal neuroprotection afforded by the acetylcholinesterase inhibitors galantamine, donepezil, and rivastigmine in SH-SY5Y neuroblastoma cells: role of nicotinic receptors.

    PubMed

    Arias, Esperanza; Gallego-Sandín, Sonia; Villarroya, Mercedes; García, Antonio G; López, Manuela G

    2005-12-01

    Donepezil, rivastigmine, and galantamine are three drugs with acetylcholinesterase (AChE)-inhibiting activity that are currently being used to treat patients suffering from Alzheimer's disease. We have studied the neuroprotective effects of these drugs, in comparison with nicotine, on cell death caused by beta-amyloid (Abeta) and okadaic acid, two models that are relevant to Alzheimer's pathology, in the human neuroblastoma cell line SH-SY5Y. Galantamine and donepezil showed a U-shaped neuroprotective curve against okadaic acid toxicity; maximum protection was achieved at 0.3 microM galantamine and at 1 microM donepezil; at higher concentrations, protection was diminished. Rivastigmine showed a concentration-dependent effect; maximum protection was achieved at 3 microM. When apoptosis was induced by Abeta25-35, galantamine, donepezil, and rivastigmine showed maximum protection at the same concentrations: 0.3, 1, and 3 microM, respectively. Nicotine also afforded protection against Abeta- and okadaic acid-induced toxicity. The neuroprotective effects of galantamine, donepezil, and nicotine were reversed by the alpha7 nicotinic antagonist methyllycaconitine but not by the alpha4beta2 nicotinic antagonist dihydro-beta-erythroidine. The phosphoinositide 3-kinase (PI3K)-Akt blocker 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) reversed the protective effects of galantamine, donepezil, and nicotine but not that of rivastigmine. In contrast, the bcl-2 antagonist ethyl[2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)]-4H-chromene-3-carboxylate (HA 14-1) reversed the protective effects of the three AChE inhibitors and that of nicotine. Our results show that galantamine, donepezil, and rivastigmine afford neuroprotection through a mechanism that is likely unrelated to AChE inhibition. Such neuroprotection seemed to be linked to alpha7 nicotinic receptors and the PI3K-Akt pathway in the case of galantamine and donepezil but not for rivastigmine

  19. Aging gauge

    DOEpatents

    Betts, Robert E.; Crawford, John F.

    1989-04-04

    An aging gauge comprising a container having a fixed or a variable sized t opening with a cap which can be opened to control the sublimation rate of a thermally sublimational material contained within the container. In use, the aging gauge is stored with an item to determine total heat the item is subjected to and also the maximum temperature to which the item has been exposed. The aging gauge container contains a thermally sublimational material such as naphthalene or similar material which has a low sublimation rate over the temperature range from about 70.degree. F. to about 160.degree. F. The aging products determined by analyses of a like item aged along with the aging gauge for which the sublimation amount is determined is employed to establish a calibration curve for future aging evaluation. The aging gauge is provided with a means for determining the maximum temperature exposure (i.e., a thermally indicating material which gives an irreversible color change, Thermocolor pigment). Because of the relationship of doubling reaction rates for increases of 10.degree. C., equivalency of item used in accelerated aging evaluation can be obtained by referring to a calibration curve depicting storage temperature on the abscissa scale and multiplier on the ordinate scale.

  20. Aging gauge

    DOEpatents

    Betts, Robert E.; Crawford, John F.

    1989-01-01

    An aging gauge comprising a container having a fixed or a variable sized t opening with a cap which can be opened to control the sublimation rate of a thermally sublimational material contained within the container. In use, the aging gauge is stored with an item to determine total heat the item is subjected to and also the maximum temperature to which the item has been exposed. The aging gauge container contains a thermally sublimational material such as naphthalene or similar material which has a low sublimation rate over the temperature range from about 70.degree. F. to about 160.degree. F. The aging products determined by analyses of a like item aged along with the aging gauge for which the sublimation amount is determined is employed to establish a calibration curve for future aging evaluation. The aging gauge is provided with a means for determining the maximum temperature exposure (i.e., a thermally indicating material which gives an irreversible color change, Thermocolor pigment). Because of the relationship of doubling reaction rates for increases of 10.degree. C., equivalency of item used in accelerated aging evaluation can be obtained by referring to a calibration curve depicting storage temperature on the abscissa scale and multiplier on the ordinate scale.

  1. Activation of recombinant human TRPV1 receptors expressed in SH-SY5Y human neuroblastoma cells increases [Ca(2+)](i), initiates neurotransmitter release and promotes delayed cell death.

    PubMed

    Lam, Patricia M W; Hainsworth, Atticus H; Smith, Graham D; Owen, Davina E; Davies, James; Lambert, David G

    2007-08-01

    The transient receptor potential (TRP) vanilloid receptor subtype 1 (TRPV1) is a ligand-gated, Ca(2+)-permeable ion channel in the TRP superfamily of channels. We report the establishment of the first neuronal model expressing recombinant human TRPV1 (SH-SY5Y(hTRPV1)). SH-SY5Y human neuroblastoma cells were stably transfected with hTRPV1 using the Amaxa Biosystem (hTRPV1 in pIREShyg2 with hygromycin selection). Capsaicin, olvanil, resiniferatoxin and the endocannabinoid anandamide increased [Ca(2+)](i) with potency (EC(50)) values of 2.9 nmol/L, 34.7 nmol/L, 0.9 nmol/L and 4.6 micromol/L, respectively. The putative endovanilloid N-arachidonoyl-dopamine increased [Ca(2+)](i) but this response did not reach a maximum. Capsaicin, anandamide, resiniferatoxin and olvanil mediated increases in [Ca(2+)](i) were inhibited by the TRPV1 antagonists capsazepine and iodo-resiniferatoxin with potencies (K(B)) of approximately 70 nmol/L and 2 nmol/L, respectively. Capsaicin stimulated the release of pre-labelled [(3)H]noradrenaline from monolayers of SH-SY5Y(hTRPV1) cells with an EC(50) of 0.6 nmol/L indicating amplification between [Ca(2+)](i) and release. In a perfusion system, we simultaneously measured [(3)H]noradrenaline release and [Ca(2+)](i) and observed that increased [Ca(2+)](i) preceded transmitter release. Capsaicin treatment also produced a cytotoxic response (EC(50) 155 nmol/L) that was antagonist-sensitive and mirrored the [Ca(2+)](I) response. This model displays pharmacology consistent with TRPV1 heterologously expressed in standard non-neuronal cells and native neuronal cultures. The advantage of SH-SY5Y(hTRPV1) is the ability of hTRPV1 to couple to neuronal biochemical machinery and produce large quantities of cells. PMID:17442052

  2. BAG2 Is Repressed by NF-κB Signaling, and Its Overexpression Is Sufficient to Shift Aβ1-42 from Neurotrophic to Neurotoxic in Undifferentiated SH-SY5Y Neuroblastoma.

    PubMed

    Santiago, Fernando E; Almeida, Maria Camila; Carrettiero, Daniel C

    2015-09-01

    Amyloid-beta (Aβ) binds to various neuronal receptors and elicits a context- and dose-dependent toxic or trophic response from neurons. The molecular mechanisms for this phenomenon are presently unknown. The cochaperone BAG2 has been shown to mediate important cellular responses to stress, including cell cycle arrest and apoptosis. Here, we use SH-SY5Y neuroblastoma cells to characterize BAG2 expression and regulation and investigate the involvement of BAG2 in Aβ1-42-mediated neurotrophism or neurotoxicity in the context of differentiation. We report that BAG2 is upregulated on differentiation of SH-SY5Y cells into neuron-like cells. This increase in BAG2 expression is accompanied by a change in response to treatment with Aβ1-42 from neurotrophic to neurotoxic. Further, overexpression of BAG2 in undifferentiated SH-SY5Y cells was sufficient to induce the change from neurotrophic to neurotoxic response. Of several transcription factors queried, the putative BAG2 promoter had a higher-than-expected occurrence of response elements (RE) for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Treatment with JSH-23, a potent inhibitor of NF-κB, caused a marked increase in BAG2 mRNA expression, suggesting that NF-κB is a repressor of BAG2 transcription in undifferentiated SH-SY5Y cells. Together, these data suggest that NF-κB-mediated modulation of BAG2 expression constitutes a "switch" that regulates the shift between the neurotrophic and neurotoxic effects of Aβ1-42. PMID:25985852

  3. Changes in plasma and hepatic lipids, small intestinal histology and pancreatic enzyme activity due to aging and dietary fiber in rats.

    PubMed

    Schneeman, B O; Richter, D

    1993-07-01

    Rats were fed either a control diet or a control diet supplemented with wheat bran, psyllium husk or oat bran to increase intake of fiber. Groups of rats were killed after 3.5, 10, 15, or 18.5 mo of consuming the diets. Plasma cholesterol and triglyceride concentrations were significantly higher in 18.5-mo-old than younger animals. Fiber supplementation did not prevent the age-related increase in lipids. Cecal weight, including contents, was higher in the psyllium husk and oat bran groups than control, and smooth muscle thickness in the ileum of psyllium husk and oat bran animals was greater than control. The score for torn villi in the small intestine was lower than expected in the wheat bran group. Amylase activity in the pancreas declined significantly with age in all groups. In aging animals fiber supplementation may enhance ileal compensation for decreases in proximal intestinal function but does not prevent age-related changes in the gut or in lipid concentrations. PMID:7686573

  4. Up/down conversion luminescence and charge compensation investigation of Ca0.5Y1-x(WO4)2:xLn3+ (Ln = Pr, Sm, Eu, Tb, Dy, Yb/Er) phosphors

    NASA Astrophysics Data System (ADS)

    Mahalingam, Venkatakrishnan; Thirumalai, Jagannathan; Krishnan, Rajagopalan; Mantha, Srinivas

    2016-01-01

    Microstructures of Ca0.5Y(1-x)(WO4)2:xLn3+ (Ln = Pr, Sm, Eu, Tb, Dy, Yb/Er) phosphors were prepared via the solid-state reaction method. X-ray diffraction, scanning electron microscopy and photoluminescence were used to characterize the prepared phosphor samples. The results reveal that the phosphor samples have single phase scheelite structures with tetragonal symmetry of I41/a. The down/up conversion photoluminescence of the Ca0.5Y(1-x)(WO4)2:xLn3+ (Ln = Pr, Sm, Eu, Tb, Dy, Yb/Er) phosphors properties reveal characteristic visible emissions. The energy transfer process, fluorescence lifetime and color coordinates are discussed in detail. Furthermore, the phosphor Ca0.5Y(1-x)(WO4)2:xPr3+ co-doped with alkali chlorides shows the enhancement of luminescence, which was found in the sodium chloride co-doped powder phosphor. The photometric characteristics indicate the suitability of the inorganic powder phosphors for solid-state lighting and display applications.

  5. S-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells.

    PubMed

    Toyama, Takashi; Abiko, Yumi; Katayama, Yuko; Kaji, Toshiyuki; Kumagai, Yoshito

    2015-01-01

    Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins. In this study, we identified proteins that undergo S-mercuration by MeHg. By combining two-dimensional SDS-PAGE, atomic absorption spectrometry and ultra performance liquid chromatography mass spectrometry (UPLC/MS/MS), we revealed that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a target for S-mercuration in human neuroblastoma SH-SY5Y cells exposed to MeHg (1 µM, 9 hr). The modification site of UCH-L1 by MeHg was Cys152, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. MeHg was shown to inhibit the catalytic activity of recombinant human UCH-L1 in a concentration-dependent manner. Knockdown of UCH-L1 indicated that this enzyme plays a critical role in regulating mono-ubiquitin (monoUb) levels in SH-SY5Y cells and exposure of SH-SY5Y cells to MeHg caused a reduction in the level of monoUb in these cells. These observations suggest that UCH-L1 readily undergoes S-mercuration by MeHg through Cys152 and this covalent modification inhibits UCH-L1, leading to the potential disruption of the maintenance of cellular monoUb levels. PMID:26558469

  6. Calpastatin overexpression reduces oxidative stress-induced mitochondrial impairment and cell death in human neuroblastoma SH-SY5Y cells by decreasing calpain and calcineurin activation, induction of mitochondrial fission and destruction of mitochondrial fusion.

    PubMed

    Tangmansakulchai, Kulvadee; Abubakar, Zuroida; Kitiyanant, Narisorn; Suwanjang, Wilasinee; Leepiyasakulchai, Chaniya; Govitrapong, Piyarat; Chetsawang, Banthit

    2016-09-01

    Calpain is an intracellular Ca(2+)-dependent protease, and the activation of calpain has been implicated in neurodegenerative diseases. Calpain activity can be regulated by calpastatin, an endogenous specific calpain inhibitor. Several lines of evidence have demonstrated a potential role of calpastatin in preventing calpain-mediated pathogenesis. Additionally, several studies have revealed that calpain activation and mitochondrial damage are involved in the cell death process; however, recent evidence has not clearly indicated a neuroprotective mechanism of calpastatin against calpain-dependent mitochondrial impairment in the process of neuronal cell death. Therefore, the purpose of this study was to investigate the potential ability of calpastatin to inhibit calpain activation and mitochondrial impairment in oxidative stress-induced neuron degeneration. Calpastatin was stably overexpressed in human neuroblastoma SH-SY5Y cells. In non-calpastatin overexpressing SH-SY5Y cells, hydrogen peroxide significantly decreased cell viability, superoxide dismutase activity, mitochondrial membrane potential, ATP production and mitochondrial fusion protein (Opa1) levels in the mitochondrial fraction but increased reactive oxygen species formation, calpain and calcineurin activation, mitochondrial fission protein (Fis1 and Drp1) levels in the mitochondrial fraction and apoptotic cells. Nevertheless, these toxic effects were abolished in hydrogen peroxide-treated calpastatin-overexpressing SH-SY5Y cells. The results of the present study demonstrate the potential ability of calpastatin to diminish calpain and calcineurin activation and mitochondrial impairment in neurons that are affected by oxidative damage. PMID:27453331

  7. Gas1 Knockdown Increases the Neuroprotective Effect of Glial Cell-Derived Neurotrophic Factor Against Glutamate-Induced Cell Injury in Human SH-SY5Y Neuroblastoma Cells.

    PubMed

    Wang, Ke; Zhu, Xue; Zhang, Kai; Zhou, Fanfan; Zhu, Ling

    2016-05-01

    Growth arrest-specific 1 (Gas1) protein acts as an inhibitor of cell growth and a mediator of cell death in nervous system during development and is also re-expressed in adult neurons during excitotoxic insult. Due to its structural similarity to the glial cell-derived neurotrophic factor family receptors α (GFRα), Gas1 is likely to interfere with the neuroprotective effect of GDNF. In the present study, we investigated the expression profile of Gas1 during glutamate insults in human SH-SY5Y neuroblastoma cells as well as the influence of Gas1 inhibition on the protective effect of GDNF against glutamate-induced cell injury. Our data showed that Gas1 expression was significantly increased with the treatment of glutamate in SH-SY5Y cells. The silencing of Gas1 by small interfering RNA promoted the protective effect of GDNF against glutamate-induced cytotoxicity as well as cell apoptosis, which effect was likely mediated through activating Akt/PI3 K-dependent cell survival signaling pathway and inhibiting mitochondrial-dependent cell apoptosis signaling pathway via Bad dephosphorylation blockade. In summary, this study showed the synergistic effect of Gas1 inhibition and GDNF against glutamate-induced cell injury in human SH-SY5Y neuroblastoma cells, which information might significantly contribute to better understanding the function of Gas1 in neuronal cells and form the basis of the therapeutic development of GDNF in treating human neurodegenerative diseases in the future. PMID:26215053

  8. Immunological Aging

    EPA Science Inventory

    Immunosenescence is associated with an increased incidence and severity of infections with common pathogens, neoplastic disease and autoimmunity. In general, aging is associated with a decline in function at the cellular level, rather than cell loss, although thymic atrophy and ...

  9. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    PubMed

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  10. Age Rules

    NASA Astrophysics Data System (ADS)

    Taylor, G. J.

    2015-10-01

    The ages of rocks from the lunar highlands vary widely, even for a single rock sample. This makes it difficult to quantitatively test ideas for early lunar differentiation and formation of the crust. Lars Borg and Amy Gaffney (Lawrence Livermore National Laboratory), and Charles Shearer (University of New Mexico) have devised a set of guidelines to apply to geochronological data that leads to a relative ranking of the reliability of the age determined for a sample. Applying their guidelines to existing data for lunar highland rocks shows an upper limit on rock ages between 4340 and 4370 million years. This is essentially the same as the so-called model ages of the formation of KREEP (a chemical component enriched in potassium, rare earth elements, and phosphorous) and of the formation of the deep source regions that melted to produce mare basalts. The numerous ages close to 4370 million years suggests a complicated and protracted cooling of the primordial lunar magma ocean or a widespread vigorous period of magmatic activity in the Moon.

  11. Plutonium aging

    SciTech Connect

    Olivas, J.D.

    1999-03-01

    The author describes the plutonium aging program at the Los Alamos National Laboratory. The aging of plutonium components in the US nuclear weapons stockpile has become a concern due to several events: the end of the cold war, the cessation of full scale underground nuclear testing as a result of the Comprehensive Test Ban Treaty (CTBT) and the closure of the Rocky Flats Plant--the site where the plutonium components were manufactured. As a result, service lifetimes for nuclear weapons have been lengthened. Dr. Olivas will present a brief primer on the metallurgy of plutonium, and will then describe the technical approach to ascertaining the long-term changes that may be attributable to self-radiation damage. Facilities and experimental techniques which are in use to study aging will be described. Some preliminary results will also be presented.

  12. Understanding aging.

    PubMed

    Strehler, B L

    2000-01-01

    Enormous advances in our understanding of human aging have occurred during the last 50 yr. From the late 19th to the mid-20th centuries only four comprehensive and important sources of information were available: 1. August Weismann's book entitled Essays on Heredity and Kindred Biological Problems (the first of these essays dealt with The Duration of Life; 1). Weissmann states (p. 10) "In the first place in regulating the length of life, the advantage to the species, and not to the individual, is alone of any importance. This must be obvious to any one who has once thoroughly thought out the process of natural selection_". 2. A highly systematized second early source of information on aging was the collection of essays edited by Cowdry and published in 1938. This 900+ page volume contains 34 chapters and was appropriately called Problems of Aging. 3. At about the same time Raymond Pearl published his book on aging (2). Pearl believed that aging was the indirect result of cell specialization and that only the germ line was resistant to aging. Unfortunately Pearl died in the late 1930s and is largely remembered now for having been the founding editor of Quarterly Review of Biology while he was at the Johns Hopkins University, this author's alma mater. 4. Alexis Carrel wrote a monumental scientific and philosophical book, Man, the Unknown (3). Carrel believed that he had demonstrated that vertebrate cells could be kept in culture and live indefinitely, a conclusion challenged by others (more on this later). PMID:22351262

  13. Aging Secret

    ERIC Educational Resources Information Center

    Journal of College Science Teaching, 2005

    2005-01-01

    The canny world of advertising has caught on to the free radical theory of aging, marketing a whole array of antioxidants for preventing anything from wrinkles to dry hair to reducing the risk of heart disease--promising to help slow the hands of time. Working with genetically engineered mice--to produce a natural antioxidant enzyme called…

  14. Gay Aging

    ERIC Educational Resources Information Center

    Haber, David

    2009-01-01

    The oldest of the baby boomers (boomers) were age 63 in 2009 and on the verge of retirement. This cohort has had a history of making societal changes throughout its life cycle, and it is unlikely that retirement, as we know it, will remain unscathed. This article highlights two events--the Stonewall Inn riots and two prominent professional…

  15. Gay aging.

    PubMed

    Haber, David

    2009-01-01

    The oldest of the baby boomers (boomers) were age 63 in 2009 and on the verge of retirement. This cohort has had a history of making societal changes throughout its life cycle, and it is unlikely that retirement, as we know it, will remain unscathed. This article highlights two events-the Stonewall Inn riots and two prominent professional associations removing homosexuality from their list of personality disorders-and how they occurred early enough in the gay boomers life cycle to change their attitudes, behaviors, and lifestyles. This article introduces the reader to a broad array of facts, research findings, and issues that inform the topic of gay aging. A summary of the discrimination and legal concerns affecting the gay community are also highlighted. Two influential community programs are identified: Services and Advocacy for Gay Elders (SAGE) and the American Society on Aging's LGBT Aging Issues Network (LAIN). Gerontological educators need to be sensitive to the needs, desires, and resources of the coming cohort of gay boomers, who are more likely to advocate for responsive services, organizations, and policies than the current cohort of gay older adults. PMID:19697188

  16. The Neuroprotective Effects of Justicidin A on Amyloid Beta25-35-Induced Neuronal Cell Death Through Inhibition of Tau Hyperphosphorylation and Induction of Autophagy in SH-SY5Y Cells.

    PubMed

    Gu, Ming-Yao; Kim, Joonki; Yang, Hyun Ok

    2016-06-01

    Justicidin A is a structurally defined arylnaphthalide lignan, which has been shown anti-cancer activity; however, the neuroprotective effect of justicidin A is still untested. In this study, we investigated the action of justicidin A on amyloid beta (Aβ)25-35-induced neuronal cell death via inhibition of the hyperphosphorylation of tau and induction of autophagy in SH-SY5Y cells. Pretreatment with justicidin A significantly elevated cell viability in cells treated with Aβ25-35. Western blot data demonstrated that justicidin A inhibited the Aβ25-35-induced up-regulation the levels of hyperphosphorylation of tau in SH-SY5Y cells. In addition, treatment with justicidin A significantly induced autophagy as measured by the increasing LC3 II/I ratio, an important autophagy marker. These studies showed that justicidin A inhibited activity of glycogen synthase kinase-3beta (GSK-3β), which is an important kinase in up-stream signaling pathways; inhibited hyperphosphorylation of tau in AD; and enhanced activity of AMP-activated protein kinase (AMPK), which is the key molecule for both hyperphosphorylation of tau and induction of autophagy. These data provide the first evidence that justicidin A protects SH-SY5Y cells from Aβ25-35-induced neuronal cell death through inhibition of hyperphosphorylation of tau and induction of autophagy via regulation the activity of GSK-3β and AMPK, and they also provide some insights into the relationship between tau protein hyperphosphorylation and autophagy. Thus, we conclude that justicidin A may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for AD. PMID:26887582

  17. Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines.

    PubMed

    Nam, Yunsung; Wie, Myung Bok; Shin, Eun-Joo; Nguyen, Thuy-Ty Lan; Nah, Seung-Yeol; Ko, Sung Kwon; Jeong, Ji Hoon; Jang, Choon-Gon; Kim, Hyoung-Chun

    2015-08-01

    Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)-induced dopaminergic toxicity in mice via genetic inhibition of PKCδ and attenuation of mitochondrial stress. In addition, we have reported that induction of mitochondrial glutathione peroxidase (GPx) is also important for neuroprotection mediated by ginsenoside Re. To extend our knowledge, we examined the effects of ginsenoside Re against MA toxicity in vitro condition using SH-SY5Y neuroblastoma cells. Treatment with ginsenoside Re resulted in significant attenuations against a decrease in the activity of GPx and an increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in glutathione (GSH) paralleled those in GPx in the same experimental condition. Consistently, ginsenoside Re treatment exhibited significant protections against cytosolic and mitochondrial oxidative damage (i.e. lipid peroxidation and protein oxidation), mitochondrial translocation of PKCδ, mitochondrial dysfunction (mitochondrial transmembrane potential and intra-mitochondrial Ca(2+)), apoptotic events [i.e., cytochrome c release from mitochondria, cleavage of caspase-3 and poly(ADP-ribose)polymerase-1, nuclear condensation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells], and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA in SH-SY5Y neuroblastoma cells. These protective effects of ginsenoside Re were comparable to those of PKCδ antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ. Our results suggest that PKCδ is a specific target for ginsenoside Re-mediated protective activity against MA toxicity in SH-SY5Y neuroblastoma cells. PMID:25523949

  18. Origin of giant permittivity and high-temperature dielectric anomaly behavior in Na{sub 0.5}Y{sub 0.5}Cu{sub 3}Ti{sub 4}O{sub 12} ceramics

    SciTech Connect

    Liang, Pengfei; Li, Yanyan; Wei, Lingling; Yang, Zupei; Zhao, Yuqing

    2013-06-14

    Na{sub 0.5}Y{sub 0.5}Cu{sub 3}Ti{sub 4}O{sub 12} ceramics prepared by the conventional solid-state reaction method under various sintering conditions were found to exhibit a giant dielectric constant over 10 000 around room temperature. Two electrical responses were observed in the combined modulus and impedance plots, indicating the presence of Maxwell-Wagner relaxation. The contributions of semiconducting grains and insulating grain boundaries (corresponding to high-frequency and low-frequency electrical response, respectively) played important roles in the dielectric properties of Na{sub 0.5}Y{sub 0.5}Cu{sub 3}Ti{sub 4}O{sub 12} ceramics. The correlations between grain boundaries resistance and low frequency dielectric loss, grains resistance and the position of dielectric loss peak were addressed. Mixed-valent structures of Cu{sup 2+}/Cu{sup 3+} and Ti{sup 3+}/Ti{sup 4+} had been determined using X-ray photoelectron spectroscopy. Electron hopping between Cu{sup 2+} and Cu{sup 3+} and electron transport in Ti{sup 3+}-O-Ti{sup 4+} paths were proposed as the origin of the semiconducting nature of Na{sub 0.5}Y{sub 0.5}Cu{sub 3}Ti{sub 4}O{sub 12} ceramics. In particular, high-temperature dielectric anomaly behavior was investigated in detail. A dielectric peak exhibiting relaxor-like behavior was observed around 200 Degree-Sign C, which was linked with the formation of oxygen vacancies. Based on the electric modulus results, this behavior was explored in the light of the defect formation and explained in terms of a competition process depending on the combinational contribution to polarization between n- and p-type carriers rather than a relaxation process.

  19. Alterations in the expression of G-proteins and regulation of adenylate cyclase in human neuroblastoma SH-SY5Y cells chronically exposed to low-efficacy mu-opioids.

    PubMed

    Ammer, H; Schulz, R

    1993-10-01

    Western-blot analysis of human neuroblastoma SH-SY5Y cells (mu- and delta-receptors) revealed the presence of the following G-protein subunits: Gi alpha 1, Gi alpha 2, Gs alpha, G(o) alpha, Gz alpha, and G beta, a pattern resembling that observed in central nervous tissue. Chronic treatment of differentiated [all-trans-retinoic acid (10 microM; 6 days)] SH-SY5Y cells with D(-)-morphine (10 microM; 3 days) significantly increased the abundance of all G-protein subunits identified. Co-incubation of morphine-exposed cells together with naloxone (10 microM; 3 days) or the mu-selective opioid antagonist CTOP (10 microM; 3 days), but not with the delta-selective antagonist ICI-174,864 (10 microM; 3 days), completely abolished this effect, suggesting that the increase in G-protein abundance is specifically mediated by mu-receptors. Moreover, the biologically inactive enantiomer L(+)-morphine (10 microM; 3 days) failed to produce a similar effect. G-protein up-regulation developed in a time- and dose-dependent manner and is most likely due to enhanced protein synthesis de novo, since concomitant treatment of the cells with cycloheximide (100 micrograms/ml; 3 days) prevented this effect. Chronic treatment with the low-efficacy mu-selective opioid peptide morphiceptin (10 microM; 3 days), but not with the highly potent mu-agonist DAGO (0.1 microM; 3 days) produced a comparable increase in G-protein abundance. Coincident with quantitative effects on G-protein levels in morphine-tolerant/dependent SH-SY5Y cells, we found elevated levels of basal, forskolin (1 microM)- and prostaglandin-E1 (1 microM)-stimulated adenylate cyclase activities. Reconstitution experiments using S49 cyc- lymphoma-cell membranes suggest that this increase is most likely due to elevated levels of functionally intact Gs. Chronic treatment with both morphine and DAGO induces high degrees of tolerance in this cell line. However, the intrinsic activity of G1 was unchanged, as assessed in functional studies

  20. [Pt(O,O'-acac)(γ-acac)(DMS)] alters SH-SY5Y cell migration and invasion by the inhibition of Na+/H+ exchanger isoform 1 occurring through a PKC-ε/ERK/mTOR Pathway.

    PubMed

    Muscella, Antonella; Vetrugno, Carla; Calabriso, Nadia; Cossa, Luca Giulio; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Marsigliante, Santo

    2014-01-01

    We previously showed that [Pt(O,O'-acac)(γ-acac)(DMS)] ([Pt(acac)2(DMS)]) exerted substantial cytotoxic effects in SH-SY5Y neuroblastoma cells, and decreased metalloproteases (MMPs) production and cells migration in MCF-7 breast cancer cells. The ubiquitously distributed sodium-hydrogen antiporter 1 (NHE1) is involved in motility and invasion of many solid tumours. The present study focuses on the effects of [Pt(acac)2(DMS)] in SH-SY5Y cell migration and also on the possibility that NHE1 may be involved in such effect. After sublethal [Pt(acac)2(DMS)] treatment cell migration was examined by wounding assay and cell invasion by transwell assay. NHE1 activity was measured in BCECF-loaded SH-SY5Y as the rate of Na+-dependent intracellular pH recovery in response to an acute acid pulse. Gelatin zymography for MMP-2/9 activities, Western blottings of MMPs, MAPKs, mTOR, S6 and PKCs and small interfering RNAs to PKC-ε/-δ mRNA were performed. Sublethal concentrations of [Pt(acac)2(DMS)] decreases NHE1 activity, inhibits cell migration and invasion and decreases expression and activity of MMP-2 and -9. [Pt(acac)2(DMS)] administered to SH-SY5Y cells provokes the increment of ROS, generated by NADPH oxidase, responsible for the PKC-ε and PKC-δ activation. Whilst PKC-δ activates p38/MAPK, responsible for the inhibition of MMP-2 and -9 secretion, PKC-ε activates a pathway made of ERK1/2, mTOR and S6K responsible for the inhibition of NHE1 activity and cell migration. In conclusion, we have shown a drastic impairment in tumour cell metastatization in response to inhibition of NHE1 and MMPs activities by [Pt(acac)2(DMS)] occurring through a novel mechanism mediated by PKC-δ/-ε activation. PMID:25372487

  1. Aging & Health.

    PubMed

    2016-09-01

    By 2050 an estimated 83.7 million Americans will be ages sixty-five and older, up from 40.3 million in 2010. The shock wave of aging Americans will have profound implications for older people, their families, health care providers, and the economy. Researchers, policy makers, health care leaders, and others are designing responses to the challenges these actuarial shifts will create. For example, delivering health care at home could help keep more older Americans out of costly emergency departments and nursing homes. But such steps require more health care providers, a broader distribution of providers than currently exists, and better use of the resources we have. PMID:27605632

  2. The combination of 1α,25dihydroxyvitaminD3 with resveratrol improves neuronal degeneration by regulating endoplasmic reticulum stress, insulin signaling and inhibiting tau hyperphosphorylation in SH-SY5Y cells.

    PubMed

    Cheng, Jinbo; Xia, Xianghou; Rui, Yehua; Zhang, Zengli; Qin, Liqiang; Han, Shufen; Wan, Zhongxiao

    2016-07-01

    Endoplasmic reticulum (ER) stress is a critical factor involved in the pathogenesis of Alzheimer's disease (AD). Vitamin D and resveratrol are two nutritional factors that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. We aimed to determine the effects of vitamin D & resveratrol on ER stress mediated neurodegeneration and whether synergistic effects existed. Tunicamycin and Aβ25-35 was utilized to induce ER stress in SH-SY5Y cells, cells were then incubated with vitamin D and resveratrol. The combination of vitamin D & resveratrol completely reversed tunicamycin and Aβ25-35 induced cytotoxicity in SH-SY5Y cells, as well as elevation in ER stress markers (i.e.GRP78, p-eIF2α and CHOP), insulin signaling disruption (i.e. elevation in p-IRS-1serine307 and reduction in p-Akt serine473) and tau phosphorylation (i.e. reduction in p-GSK3β serine9, and elevation in p-Tau serine396 &404). Further studies are required to clarify whether the observed synergistic effects in the present study would also existed in vivo, this will lay scientific foundation whether the combination of vitamin D with resveratrol might be an effective maneuver in the treatment of AD in human subjects. PMID:27133915

  3. Effect of Nb doping on superconducting and magnetic properties of RuSr 2(Gd 1.5- yEu yCe 0.5)Cu 2O z

    NASA Astrophysics Data System (ADS)

    Lee, H. K.; Williams, G. V. M.

    2004-11-01

    We performed resistivity and magnetization measurements on the ruthenocuprates (Ru 1- xNb x)Sr 2(Gd 1.4Ce 0.6)Cu 2O z ( x = 0-0.5) and (Ru 0.5Nb 0.5)Sr 2(Gd 1.5- yEu yCe 0.5)Cu 2O z ( y = 0-1.5). It is found that the Nb substitution for Ru depresses superconductivity only slightly from Tc = 27 K for x = 0 to Tc = 24 K for x = 0.5, but significantly reduces the ferromagnetic component. In contrast to the Nb-free sample, a partial evolution of the Meissner state followed by a reentrance of the magnetization is observed in the field-cooled magnetization measurements of the Nb-doped samples. The magnetization measurements on the (Ru 0.5Nb 0.5)Sr 2(Gd 1.5- yEu yCe 0.5)Cu 2O z system indicate that the reentrant behavior of the magnetization below Tc is caused by the paramagnetic contribution of the Gd 3+ ions and the Meissner effect can be seen more clearly after suppressing the paramagnetic response of the sublattice of Gd 3+ ions.

  4. MicroRNA-H4-5p encoded by HSV-1 latency-associated transcript promotes cell proliferation, invasion and cell cycle progression via p16-mediated PI3K-Akt signaling pathway in SHSY5Y cells

    PubMed Central

    Zhao, Huiliang; Zhang, Chunying; Hou, Guangjun; Song, Jijun

    2015-01-01

    Herpes simplex virus 1 (HSV-1) microRNAs (miRNAs) mostly located in transcription-associated transcript (LAT) region have been identified that play critical roles in the intricate host-pathogen interaction networks. Increasing evidences throw new insight into the role of miRNA-mediated miRNA-mRNA cross-talk in HSV-1 latent or acute infection. In the present study, we found that hsv-1 miR-H4-5p (here termed as miR-H4b) can down-regulate the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A, p16) in neuroblastoma (SHSY5Y) cell lines. Decreased expression of miR-H4b was directly related to attenuated cell proliferation and invasion as well as malfunction of cell cycle in recombinant SHSY5Y cells that stably expressing miR-H4b. Bioinformatics analysis and luciferase assays demonstrated miR-H4b can directly target p16 mRNA. MiR-H4b exerts its pro-proliferation function through inhibition of the p16-related PI3K-Akt pathways. Our findings provide, for the first time, significant clues regarding the role of herpesvirus-encoded miRNAs as a viral modulator to host cells. PMID:26221296

  5. The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling

    PubMed Central

    Saez-Atienzar, S; Bonet-Ponce, L; Blesa, J R; Romero, F J; Murphy, M P; Jordan, J; Galindo, M F

    2014-01-01

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been associated with Parkinson's disease, and its inhibition opens potential new therapeutic options. Among the drug inhibitors of both wild-type and mutant LRRK2 forms is the 2-arylmethyloxy-5-subtitutent-N-arylbenzamide GSK257815A. Using the well-established dopaminergic cell culture model SH-SY5Y, we have investigated the effects of GSK2578215A on crucial neurodegenerative features such as mitochondrial dynamics and autophagy. GSK2578215A induces mitochondrial fragmentation of an early step preceding autophagy. This increase in autophagosome results from inhibition of fusion rather than increases in synthesis. The observed effects were shared with LRRK2-IN-1, a well-described, structurally distinct kinase inhibitor compound or when knocking down LRRK2 expression using siRNA. Studies using the drug mitochondrial division inhibitor 1 indicated that translocation of the dynamin-related protein-1 has a relevant role in this process. In addition, autophagic inhibitors revealed the participation of autophagy as a cytoprotective response by removing damaged mitochondria. GSK2578215A induced oxidative stress as evidenced by the accumulation of 4-hydroxy-2-nonenal in SH-SY5Y cells. The mitochondrial-targeted reactive oxygen species scavenger MitoQ positioned these species as second messengers between mitochondrial morphologic alterations and autophagy. Altogether, our results demonstrated the relevance of LRRK2 in mitochondrial-activated pathways mediating in autophagy and cell fate, crucial features in neurodegenerative diseases. PMID:25118928

  6. Enhanced sinterability and conductivity of BaZr0.3Ce0.5Y0.2O3-δ by addition of bismuth oxide for proton conducting solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Gui, Liangqi; Ling, Yihan; Li, Geng; Wang, Zhihao; Wan, Yanhong; Wang, Ranran; He, Beibei; Zhao, Ling

    2016-01-01

    The effect of bismuth oxide addition on the sintering behavior and electrical properties of BaZr0.3Ce0.5Y0.2O3-δ (BZCY) as an electrolyte for proton conducting solid oxide fuel cells (H-SOFCs) is studied. The introduction of Bi2O3 is beneficial to improving sinterability of BZCY, resulting in high density. Meanwhile, the conductivity test indicates that BaZr0.3Ce0.5Y0.2O3-δ - 2 mol% Bi2O3 (BZCY-2) promises the highest conductivities. Further, single cells with BZCY-2 as the electrolyte are fabricated and evaluated. The cell with BZCY-2 presents excellent power densities, which reaches 0.67, 0.44, and 0.27 mW cm-2 at 700, 650, and 600 °C, respectively. The conductivities of BZCY-2 film are higher than BZCY in this work and other reported BZCY films. The encouraging results suggest that the addition of a small amount (2 mol%) of Bi2O3 to BZCY can significantly promote sinterability and electrical conductivity for H-SOFCs.

  7. Ternary Phosphide Ho 2Cu 6- xP 5- y, Its Crystal Structure, and REm+ n(Cu 2P 3) m(Cu 4P 2) n Relationship with Other Rhombohedral Rare-Earth Copper Phosphides

    NASA Astrophysics Data System (ADS)

    Mozharivskyj, Yurij; Kuz'ma, Yurij B.

    2000-04-01

    Crystals of the phosphide Ho2Cu6-xP5-y (x=0.41, y=0.50) have been prepared by annealing pressed powders of the elements at 800°C for 2 weeks. The structure was determined by single-crystal methods: space group Roverline3m (No. 166), Z=3, a=3.976(1) Å, c=40.554(8) Å, R=0.045 for 243 independent reflections [F>4σ(F)]. The unit cell of Ho2Cu6-xP5-y can be built from a close packing of Ho atoms and fragments of Cu3P, with one of the fragments containing additional P atoms. It can be also considered as an intercalation of additional P atoms in the YbCu3-xP2 structure (P. Klüfers, A. Mewis, and H. U. Schuster, Z. Kristallogr. 149, 211 (1979)). The REm+n(Cu2P3)m(Cu4P2)n relationship with other rare-earth copper phosphides, having similar structural characteristics is discussed.

  8. Dimerumic Acid and Deferricoprogen Activate Ak Mouse Strain Thymoma/Heme Oxygenase-1 Pathways and Prevent Apoptotic Cell Death in 6-Hydroxydopamine-Induced SH-SY5Y Cells.

    PubMed

    Tseng, Wei-Ting; Hsu, Ya-Wen; Pan, Tzu-Ming

    2016-08-01

    Parkinson's disease (PD) is a neurodegenerative disorder, which can be modeled using the neurotoxin 6-hydroxydopamine (6-OHDA) to generate oxidative stress. Here, we studied the effects of the antioxidants deferricoprogen (DFC) and dimerumic acid (DMA), produced by rice fermented with Monascus purpureus NTU 568, on 6-OHDA-induced apoptosis in SH-SY5Y cells and their potential protective mechanisms. DMA and DFC inhibited 6-OHDA-induced apoptosis and cellular reactive oxygen species (ROS) in SH-SY5Y human neuroblastoma cells. Molecular analysis demonstrated associated upregulation of the Ak mouse strain thymoma (Akt), heme oxygenase-1 (HO-1), and signal-regulated kinase (ERK) pathways along with inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and p38 pathways and altered homodimeric glycoprotein, N-methyl-d-aspartate (NMDA) receptor, and immunoglobulin Fc receptor gene expression. These results suggested that the neuroprotection elicited by DMA and DFC against 6-OHDA-induced neurotoxicity was associated with the Akt, MAPK, and HO-1 pathways via regulating the gene expression of NMDA receptor, homodimeric glycoprotein, and immunoglobulin Fc receptor. PMID:27431098

  9. Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death.

    PubMed

    Zhu, Guoqi; Wang, Xuncui; Wu, Shengbing; Li, Qinglin

    2012-03-01

    In an attempt to clarify the protective effect of puerarin on toxin-insulted dopaminergic neuronal death, this present study was carried out by using a typical Parkinson's disease (PD) model - 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced dopaminergic SH-SY5Y cellular model. Data are presented, which showed that puerarin up-regulated Akt phosphorylation in both of MPP(+)-treated and non-MPP(+)-treated cells. The presence of PI3K inhibitor LY294002 completely blocked puerarin-induced activation of Akt phosphorylation. Moreover, puerarin decreased MPP(+)-induced cell death, which was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002. We further demonstrated that puerarin protected against MPP(+)-induced p53 nuclear accumulation, Puma (p53-upregulated mediator of apoptosis) and Bax expression and caspase-3-dependent programmed cell death (PCD). This protection was blocked by applying a PI3K/Akt inhibitor. Additionally, it was Pifithrin-α, but not Pifithrin-μ, which blocked MPP(+)-induced Puma and Bax expression, caspase-3 activation and cell death. Collectively, these data suggest that the activation of PI3K/Akt pathway is involved in the protective effect of puerarin against MPP(+)-induced neuroblastoma SH-SY5Y cell death through inhibiting nuclear p53 accumulation and subsequently caspase-3-dependent PCD. Puerarin might be a potential therapeutic agent for PD. PMID:22265823

  10. Celastrol from 'Thunder God Vine' protects SH-SY5Y cells through the preservation of mitochondrial function and inhibition of p38 MAPK in a rotenone model of Parkinson's disease.

    PubMed

    Choi, Bong-Suk; Kim, Hyool; Lee, Hyo Jeong; Sapkota, Kumar; Park, Se Eun; Kim, Seung; Kim, Sung-Jun

    2014-01-01

    Celastrol, a potent natural triterpene and one of the most promising medicinal molecules, is known to possess a broad range of biological activity. Rotenone, a pesticide and complex I inhibitor, is commonly used to produce experimental models of Parkinson's disease both in vivo and in vitro. The present study was designed to examine the effects of celastrol on cell injury induced by rotenone in the human dopaminergic cells and to elucidate the possible mechanistic clues in its neuroprotective action. We demonstrate that celastrol protects SH-SY5Y cells from rotenone-induced cellular injury and apoptotic cell death. Celastrol also prevented the increased generation of reactive oxygen species and mitochondrial membrane potential (ΔΨm) loss induced by rotenone. Similarly, celastrol treatment inhibited cytochrome c release, Bax/Bcl-2 ratio changes, and caspase-9/3 activation. Celastrol specifically inhibited rotenone-evoked p38 mitogen-activated protein kinase activation in SH-SY5Y cells. These data suggest that celastrol may serve as a potent agent for prevention of neurotoxin-induced neurodegeneration through multiple mechanisms and thus has therapeutic potential for the treatment of neurodegenerative diseases. PMID:24214023

  11. Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling

    PubMed Central

    Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

    2013-01-01

    Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways. PMID:23764850

  12. Age Relationship

    NASA Technical Reports Server (NTRS)

    2006-01-01

    12 June 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a group of impact craters in Aonia Planum, Mars. Remarkably, two of the craters are approximately equal in size, however, they clearly differ in age. The left (west) crater has a well-defined rim and its ejecta blanket overlies part of the less pronounced crater to its immediate east. The one with the ejecta blanket is younger. Other circular depressions in this bouldery scene are also old, eroded impact craters.

    Location near: 59.5oS, 78.5oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Autumn

  13. Aging blepharoplasty.

    PubMed

    Cho, Inchang

    2013-09-01

    In performing upper blepharoplasty in the elderly, looking younger and keeping the eyelids harmonious with the rest of the face have to be achieved at the same time. The most important goal in upper blepharoplasty for aging is correcting the drooping upper eyelid skin, and in this process, the surgeon may or may not create a double eyelid fold. The pros and cons have to be fully discussed with the patient, but the author personally prefers creating a double fold unless the patient refuses, because it is efficient in correcting and preventing further drooping of the skin. In most patients, the brow is elevated to compensate for the drooping eyelid, and when the drooping is corrected, brow ptosis may ensue. The surgeon has to prepare for these consequences before performing the procedure, and estimate the exact amount of skin to be excised. In the elderly, the skin and the orbicularis oculi muscle is thin, with a decreased amount of subcutaneous fat and retro-orbicularis oculi fat, and in most cases, excision of the skin alone is enough to correct the deformity. Removing large portions of soft tissue may also prolong the recovery period. Unlike younger patients, the lower skin flap should not be stretched too much in the elderly, as it may create an aggressive looking appearance. A few wrinkles in the lower flap should remain untouched to create a natural look. In this article, the author's own methods of performing an aging blepharoplasty are described specifically, with a step-by-step guide and surgical tips. PMID:24086798

  14. Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats.

    PubMed

    Leeuwenburgh, C; Hansen, P; Shaish, A; Holloszy, J O; Heinecke, J W

    1998-02-01

    Many lines of evidence implicate oxidative damage in aging. Possible pathways include reactions that modify aromatic amino acid residues on proteins. o-Tyrosine is a stable marker for oxidation of protein-bound phenylalanine by hydroxyl radical, whereas 3-nitrotyrosine is a marker for oxidation of protein-bound tyrosine by reactive nitrogen species. To test the hypothesis that proteins damaged by hydroxyl radical and reactive nitrogen accumulate with aging, we used isotope dilution gas chromatography-mass spectrometry to measure levels of o-tyrosine and 3-nitrotyrosine in heart, skeletal muscle, and liver from young adult (9 mo) and old (24 mo) female Long-Evans/Wistar hybrid rats. We also measured these markers in young adult and old rats that received antioxidant supplements (alpha-tocopherol, beta-carotene, butylated hydroxytoluene, and ascorbic acid) from the age of 5 mo. We found that aging did not significantly increase levels of protein-bound o-tyrosine or 3-nitrotyrosine in any of the tissues. Antioxidant supplementation had no effect on the levels of protein-bound o-tyrosine and 3-nitrotyrosine in either young or old animals. These observations indicate that the o-tyrosine and 3-nitrotyrosine do not increase significantly in heart, skeletal muscle, and liver in old rats, suggesting that proteins damaged by hydroxyl radical and reactive nitrogen species do not accumulate in these tissues with advancing age. PMID:9486304

  15. Coincident signalling between the Gi/Go-coupled delta-opioid receptor and the Gq-coupled m3 muscarinic receptor at the level of intracellular free calcium in SH-SY5Y cells.

    PubMed

    Yeo, A; Samways, D S; Fowler, C E; Gunn-Moore, F; Henderson, G

    2001-03-01

    In SH-SY5Y cells, activation of delta-opioid receptors with [D-Pen(2,5)]-enkephalin (DPDPE; 1 microM) did not alter the intracellular free Ca(2+) concentration [Ca(2+)](i). However, when DPDPE was applied during concomitant Gq-coupled m3 muscarinic receptor stimulation by carbachol or oxotremorine-M, it produced an elevation of [Ca(2+)](i). The DPDPE-evoked increase in [Ca(2+)](i) was abolished when the carbachol-sensitive intracellular Ca(2+) store was emptied. There was a marked difference between the concentration-response relationship for the elevation of [Ca(2+)](i) by carbachol (EC(50) 13 microM, Hill slope 1) and the concentration-response relationship for carbachol's permissive action in revealing the delta-opioid receptor-mediated elevation of [Ca(2+)] (EC(50) 0.7 mM; Hill slope 1.8). Sequestration of free G protein beta gamma dimers by transient transfection of cells with a beta gamma binding protein (residues 495-689 of the C terminal tail of G protein-coupled receptor kinase 2) reduced the ability of delta opioid receptor activation to elevate [Ca(2+)](i). However, DPDPE did not elevate either basal or oxotremorine-M-evoked inositol phosphate production indicating that delta-opioid receptor activation did not stimulate phospholipase C. Furthermore, delta-opioid receptor activation did not result in the reversal of muscarinic receptor desensitization, membrane hyperpolarization or stimulation of sphingosine kinase. There was no coincident signalling between the delta-opioid receptor and the lysophosphatidic acid receptor which couples to elevation of [Ca(2+)](i) in SH-SY5Y cells by a PLC-independent mechanism. In SH-SY5Y cells the coincident signalling between the endogenously expressed delta-opioid and m3 muscarinic receptors appears to occur in the receptor activation-Ca(2+) release signalling pathway at a step after the activation of phospholipase C. PMID:11259487

  16. Spin and magnetization compensation points in LPE-grown Y 2.4Eu 0.6Ga yFe 5-yO 12 garnet thin films

    NASA Astrophysics Data System (ADS)

    Singh, L. N.; Srivastava, C. M.

    1993-11-01

    The effective g-factor, geff, the uniaxial anisotropy, Hu, Gilbert's damping parameter, α, and linewidths Δ H‖ and Δ H⊥ for liquid phase epitaxially grown thin films of composition Eu 0.6Y 2.4Ga yFe 5- yO 12 (0.9⩽ y ⩽1.6) have been investigated in the spin compensation region. It is found that the spin compensation point ( yS) occurs at y = 1.29, while the magnetization compensation point ( ym) occurs at y = 1.22 giving yS- ym = 0.07. The damping parameter α as well as γ eff/α for both the parallel and perpendicular resonance configurations are found to diverge at the S-compensation point while the anisotropy field diverges at the M-compensation point.

  17. Luminescent properties of sol-gel processed red-emitting phosphor Ca0.6 Sr0.4-1.5x-0.5y Mo0.4  W0.6 O4:Eux Liy.

    PubMed

    Li, Fei; Xie, Huidong; Xi, Haihong; Dang, Fangfang; Wang, Xiaochang

    2015-08-01

    A series of red-emitting phosphors Ca0.6Sr(0.4-1.5x-0.5y)Mo0.4W0.6O4:Eux Liy (x = 0.02-0.12, y = 0-0.12) has been synthesized by a sol-gel method. The effects of calcining temperature, concentrations of Li(+) and Eu(3+) , and compensation ions on the luminescent properties were investigated. X-ray diffraction and scanning electron microscopic results showed that as-prepared phosphors were of single phase with several microns. The Li(+) compensated compositions showed remarkably intense red emission at 619 nm. The emission intensity of the series reached maximum for compositions at x = 0.08 and y = 0.08 when the calcining temperature was 900 °C. PMID:25339264

  18. Nd0.5Bi2.5Fe5- y Ga y O12 thin films on Gd3Ga5O12 substrates prepared by metal-organic decomposition

    NASA Astrophysics Data System (ADS)

    Sasaki, Michimasa; Lou, Gengjian; Liu, Qi; Ninomiya, Minami; Kato, Takeshi; Iwata, Satoshi; Ishibashi, Takayuki

    2016-05-01

    Highly Bi-substituted neodymium iron gallium garnet thin films with a Bi content of 2.5, Nd0.5Bi2.5Fe5- y Ga y O12 (NBIGG) with y = 0-1, on gadolinium gallium garnet (111) and (100) substrates have been prepared by metal-organic decomposition. Magnetic properties and magnetic anisotropy energies were measured using an alternating field gradient magnetometer and by magnetic torque measurement, respectively. Faraday rotation spectra and hysteresis loops were measured using a Faraday rotation spectrometer. The magnetization of NBIGG thin films exhibiting a large Faraday rotation of 10-15°/µm decreased with increasing Ga content, resulting in increased effective magnetic anisotropy energy K eff. The dependence of the magnetic anisotropies on the Ga content is discussed in terms of the reverse magnetostrictive effect caused by thermal stress as well as the magnetocrystalline and shape anisotropies.

  19. [Effect of alpha-conotoxin MII and its N-terminal derivatives on Ca2+ and Na+ signals induced by nicotine in neuroblastoma cell line SH-SY5Y].

    PubMed

    Surin, A M; Kriukova, E V; Strukov, A S; Zhmak, M N; Talka, R; Tuominen, R; Salminen, O; Khiroug, L; Kasheverov, I E; Tsetlin, V I

    2012-01-01

    Nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation ofintracellular Ca2+-dependent processes in cells both in normal and pathological states, alpha-Conotoxins isolated from Conus snails venom are a valuable tool for the study of pharmacological properties and functional role of nAChRs. In the present study the alpha-conotoxin MII analogue with the additional tyrosine attached to the N terminus (Y0-MII) was prepared. Also we synthesized analogs with the N-terminal glycine residue labeled with the Bolton- Hunter reagent (BH-MII) or fluorestsein isothiocyanate (FITC-MII). Fluorescence microscopy studies of the neuroblastoma SH-SY5Y cells loaded with Ca2+ indicator Fura-2 or with Ca2+ and Na+ indicators Fluo-4 and SBFI were performed to examine effect of MII modification on its ability to inhibit nicotin-induced increases in intracellular free Ca2+ and Na+ concentrations ([Ca2+] and [Na+]i respectively). Monitoring of individual cell [Ca2+]i and [Na+]i signals revealed different kinetics of [Ca2+]i and [Na+]i rise and decay in responses to brief nicotine (Nic) applications (10-30 microM, 3-5 min), which indicates to different mechanisms of Ca2+ and Na+ homeostasis control in SH-SY5Y cells. MII inhibited in concentration-dependent manner the both [Ca2+]i and [Na+]i increase induced by Nic. Additional tyrosine in the Y0-MII or, especially, more sizeable label in FITC-MII significantly reduced the inhibitory effect of MII. Whereas the efficiency of the Ca2+ response inhibition by BH-MII was found to be close to the efficiency of its inhibition by natural alpha-conotoxin MII, radioiodinated derivatives BH-MII can be used in radioligand assay. PMID:22792725

  20. Salsolinol Damaged Neuroblastoma SH-SY5Y Cells Induce Proliferation of Human Monocyte THP-1 Cells Through the mTOR Pathway in a Co-culture System.

    PubMed

    Wang, Fuli; Ni, Junjun; Wang, Xianghan; Xie, Bingjie; Feng, Chengcheng; Zhao, Sibo; Saeed, Yasmeem; Qing, Hong; Deng, Yulin

    2015-05-01

    Despite extensive efforts to study the inflammatory process in the central nervous system of Parkinson's disease (PD) patients, little is known about the role of peripheral blood mononuclear cells (PBMCs) in PD. In the present study, we used an in vitro co-culture system to study the role of the human monocyte cell line THP-1 in medium conditioned by the neuroblastoma cell line SH-SY5Y damaged with the endogenous neurotoxin 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (Salsolinol, Sal) in co-culture with the human glioma cell line U87. For this purpose, SH-SY5Y and U87 co-cultures were treated with Sal, and this conditioned medium containing mediators, including the potential effector CCL2, was isolated and applied to THP-1 cells. This treatment resulted in approximately 19 % cell proliferation as well as activation of mTOR and induction of phosphorylated 4E-BP1, S6K1, PI3K, and AKT proteins. Treatment with rapamycin, an mTOR inhibitor, attenuated the proliferation of THP-1 cells. U87 glial cells were essential for this as medium conditioned without them had no effect on THP-1 cells. These results suggest a positive effect of THP-1 cells on Sal-induced neurotoxicity in a cellular model of PD and this is likely mediated by the enhancement of cell proliferation through activation of the mTOR signaling pathway. Hence, PBMCs and their mTOR signaling pathway could be of therapeutic benefit in treating the endogenous neurotoxin-induced neuroinflammation in PD. PMID:25773262

  1. Fentanyl activates hypoxia-inducible factor 1 in neuronal SH-SY5Y cells and mice under non-hypoxic conditions in a μ-opioid receptor-dependent manner.

    PubMed

    Daijo, Hiroki; Kai, Shinichi; Tanaka, Tomoharu; Wakamatsu, Takuhiko; Kishimoto, Shun; Suzuki, Kengo; Harada, Hiroshi; Takabuchi, Satoshi; Adachi, Takehiko; Fukuda, Kazuhiko; Hirota, Kiichi

    2011-09-30

    Hypoxia-inducible factor 1 (HIF-1) is the main transcription factor responsible for hypoxia-induced gene expression. Perioperative drugs including anesthetics have been reported to affect HIF-1 activity. However, the effect of fentanyl on HIF-1 activity is not well documented. In this study, we investigated the effect of fentanyl and other opioids on HIF-1 activity in human SH-SY5Y neuroblastoma cells, hepatoma Hep3B cells, lung adenocarcinoma A549 cells and mice. Cells were exposed to fentanyl, and HIF-1 protein expression was examined by Western blot analysis using anti-HIF-1α and β antibodies. HIF-1-dependent gene expression was investigated by semi-quantitative real-time reverse transcriptase (RT)-PCR (qRT-PCR) and luciferase assay. Furthermore, fentanyl was administered intraperitoneally and HIF-1-dependent gene expression was investigated by qRT-PCR in the brains and kidneys of mice. A 10-μM concentration of fentanyl and other opioids, including 1 μM morphine and 4 μM remifentanil, induced HIF-1α protein expression and HIF-1 target gene expression in an opioid receptor-dependent manner in SH-SY5Y cells with activity peaking at 24h. Fentanyl did not augment HIF-1α expression during hypoxia-induced induction. HIF-1α stabilization assays and experiments with cycloheximide revealed that fentanyl increased translation from HIF-1α mRNA but did not stabilize the HIF-1α protein. Furthermore, fentanyl induced HIF-1 target gene expression in the brains of mice but not in their kidneys in a naloxone-sensitive manner. In this report, we describe for the first time that fentanyl, both in vitro and in vivo, induces HIF-1 activation under non-hypoxic conditions, leading to increases in expression of genes associated with adaptation to hypoxia. PMID:21703258

  2. Impact of Inhomogeneous Static Magnetic Field (31.7–232.0 mT) Exposure on Human Neuroblastoma SH-SY5Y Cells during Cisplatin Administration

    PubMed Central

    Mobasheri, Hamid; Dini, Luciana

    2014-01-01

    Beneficial or adverse effects of Static Magnetic Fields (SMFs) are a large concern for the scientific community. In particular, the effect of SMF exposure during anticancer therapies still needs to be fully elucidated. Here, we evaluate the effects of SMF at induction levels that cisPt-treated cancer patients experience during the imaging process conducted in Low field (200–500 mT), Open field (300–700 mT) and/or inhomogeneous High field (1.5–3 T) Magnetic Resonance Imaging (MRI) machines. Human adrenergic neuroblastoma SH-SY5Y cells treated with 0.1 µM cisPt (i.e. the lowest concentration capable of inducing apoptosis) were exposed to SMF and their response was studied in vitro. Exposure of 0.1 µM cisPt-treated cells to SMF for 2 h decreased cell viability (30%) and caused overexpression of the apoptosis-related cleaved caspase-3 protein (46%). Furthermore, increase in ROS (Reactive Oxygen Species) production (23%) and reduction in the number of mitochondria vs controls were seen. The sole exposure of SMF for up to 24 h had no effect on cell viability but increased ROS production and modified cellular shape. On the other hand, the toxicity of cisPt was significantly prevented during 24 h exposure to SMF as shown by the levels of cell viability, cleaved caspase-3 and ROS production. In conclusion, due to the cytoprotective effect of 31.7–232.0 mT SMF on low-cisPt-concentration-treated SH-SY5Y cells, our data suggest that exposure to various sources of SMF in cancer patients under a cisPt regimen should be strictly controlled. PMID:25423171

  3. Paliperidone Protects SH-SY5Y Cells Against MK-801-Induced Neuronal Damage Through Inhibition of Ca(2+) Influx and Regulation of SIRT1/miR-134 Signal Pathway.

    PubMed

    Zhu, Dexiao; Zhang, Jing; Wu, Jintao; Li, Guibao; Yao, Wei; Hao, Jing; Sun, Jinhao

    2016-05-01

    Schizophrenia is a serious psychotic disease. Recently, increasing evidences support that neurodegeneration occurs in the brain of schizophrenia patients with progressive morphological changes. Paliperidone, an atypical antipsychotic drug, could attenuate psychotic symptom and protect neurons from different stressors. However, the underlying mechanisms are largely unknown. In this study, we used SH-SY5Y cells to evaluate the neuroprotective capability of paliperidone against the neurotoxicity induced by N-methyl-D-aspartate receptor antagonist, MK-801. And, we also explored the possible molecular mechanism. Neurotoxicity of 100 μM MK-801, which reduced the cell viability, was diminished by 100 μM paliperidone using MTT and LDH assays (both p < 0.05). Analysis with Hoechst 33342/PI double staining demonstrated that exposure to MK-801 (100 μM) for 24 h led to the death of 30 % of cultured cells (p < 0.05). Moreover, the patch clamp technique was employed to detect voltage calcium channel changes; the results showed that paliperidone effectively blocked the Ca(2+) influx through inhibiting the voltage-gated calcium channels (p < 0.05). Furthermore, paliperidone significantly reversed MK-801 induced increase of SIRT1 and decrease of miR-134 expression (both p < 0.05). Finally, SIRT1 inhibitor nicotinamide blocked MK-801 injury effects and suppressed miR-134 expression. Taken together, our results demonstrated that paliperidone could protect SH-SY5Y cells against MK-801 induced neurotoxicity via inhibition of Ca(2+) influx and regulation of SIRT1/miR-134 pathway, providing a promising and potential therapeutic target for schizophrenia. PMID:26055227

  4. Gold nanostars coated with neutral and charged polyethylene glycols: A comparative study of in-vitro biocompatibility and of their interaction with SH-SY5Y neuroblastoma cells.

    PubMed

    Pallavicini, Piersandro; Cabrini, Elisa; Cavallaro, Gennara; Chirico, Giuseppe; Collini, Maddalena; D'Alfonso, Laura; Dacarro, Giacomo; Donà, Alice; Marchesi, Nicoletta; Milanese, Chiara; Pascale, Alessia; Sironi, Laura; Taglietti, Angelo

    2015-10-01

    Gold nanostars (GNS) have been coated with four different polyethylene glycols (PEGs) equipped with a -SH function for grafting on the gold surface. These PEGs have different chain lengths with average MW=2000, 3000, 5000 and average number of -O-CH2-CH2 - units 44, 66, and 111, respectively. Two are neutral and two are terminated with -COOH and -NH2 functions, thus bearing negative and positive charges at physiological pH, thanks to the formation of carboxylate and ammonium groups. The negative charge of the GNS coated with PEG carboxylate has also been exploited to further coat the GNS with the PAH (polyallylamine hydrochloride) cationic polymer. Vitality tests have been carried out on SH-SY5Y cells treated with the five differently coated GNS for 4, 24, and 48 h, at Au concentrations ranging from 1.25 to 100 μg/mL. The same tests have been repeated with the pure PEGs and PAH. Excellent biocompatibility was found for all PEGs, independently on charge and chain length, both for coated GNS and for the pure polymers. On the contrary, poor biocompatibility was found for PAH overcoated GNS and for pure PAH, although the latter only at high concentrations. Exploiting the two-photon luminescence of GNS, we have found by confocal laser scanning microscopy that when GNS are coated with PEGs they do not enter SH-SY5Y cells, while when overcoated with PAH they massively penetrate into the cytoplasm. This causes cell death by dramatically changing cell morphology, as demonstrated also by atomic force microscopy. PMID:25997575

  5. MS-275 inhibits aroclor 1254-induced SH-SY5Y neuronal cell toxicity by preventing the formation of the HDAC3/REST complex on the synapsin-1 promoter.

    PubMed

    Formisano, Luigi; Guida, Natascia; Laudati, Giusy; Mascolo, Luigi; Di Renzo, Gianfranco; Canzoniero, Lorella M T

    2015-02-01

    Polychlorinated biphenyl (PCB) exposure has been associated with neurodegenerative diseases, such as Parkinson's disease, amyotrophic lateral sclerosis, and dementia. Neuronal death elicited by the PCB mixture Aroclor 1254 (A1254) has been attributed to an increase in RE-1-silencing transcription factor (REST), which, in turn, correlates with a decrease in the synapsin-1 promoter gene. Although histone deacetylase (HDAC) inhibitors are known to be neuroprotective in several neurologic disorders, the core mechanisms governing this effect are not yet understood. Here, to examine how HDAC class I [N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)aminomethyl]-benzamide (MS-275)] and HDAC class II [3-[5-(3-(3-fluorophenyl)-3-oxopropen-1-yl)-1-methyl-1H-pyrrol-2-yl]-N-hydroxy-2-propenamide (MC-1568)] inhibitors prevent A1254-induced neuronal cell death, we exposed SH-SY5Y neuroblastoma cells to A1254. Exposure to A1254 (30.6 μM) for 24 and 48 hours resulted in a time-dependent cell death. Indeed, after 48 hours, MS-275, but not MC-1568, reverted A1254-induced cell death in a dose-dependent manner. Furthermore, A1254 significantly increased HDAC3, but not HDAC1 or HDAC2. Interestingly, REST physically interacted with HDAC3 after A1254 exposure. Chromatin immunoprecipitation assays revealed that MS-275 reverted the increased levels of HDAC3 binding and decreased acetylation of histone H3 within the synapsin-1 promoter region, thus reverting synapsin-1 mRNA reduction. Moreover, REST knockdown by small interfering RNA (siRNA) prevented HDAC3 from binding to the synapsin-1 promoter. Likewise, HDAC3 siRNA significantly reduced A1254-induced cell toxicity in SH-SY5Y cells and cortical neurons. Hence, this study demonstrates that inhibition of HDAC class I attenuates A1254-induced neuronal cell death by preventing HDAC3 binding and histone deacetylation within the synapsin-1 promoter region. PMID:25467131

  6. SEECAL: Program to calculate age-dependent

    SciTech Connect

    Cristy, M.; Eckerman, K.F.

    1993-12-01

    This report describes the computer program SEECAL, which calculates specific effective energies (SEE) to specified target regions for ages newborn, 1 y, 5 y, 10 y, 15 y, a 70-kg adult male, and a 58-kg adult female. The dosimetric methodology is that of the International Commission on Radiological Protection (ICRP) and is generally consistent with the schema of the Medical Internal Radiation Dose committee of the US Society of Nuclear Medicine. Computation of SEEs is necessary in the computation of equivalent dose rate in a target region, for occupational or public exposure to radionuclides taken into the body. Program SEECAL replaces the program SEE that was previously used by the Dosimetry Research Group at Oak Ridge National Laboratory. The program SEE was used in the dosimetric calculations for occupational exposures for ICRP Publication 30 and is limited to adults. SEECAL was used to generate age-dependent SEEs for ICRP Publication 56, Part 1. SEECAL is also incorporated into DCAL, a radiation dose and risk calculational system being developed for the Environmental Protection Agency. Electronic copies of the program and data files and this report are available from the Radiation Shielding Information Center at Oak Ridge National Laboratory.

  7. Dating earthquakes with high-precision thorium-230 ages of very young corals

    NASA Technical Reports Server (NTRS)

    Edwards, R. Lawrence; Wasserburg, G. J.; Taylor, F. W.

    1988-01-01

    Three corals from Vanuatu Islands, whose ages were known from counting annual growth bands, were analyzed by Th-230 age analysis to asses the accuracy of the Th-230 method. The comparison of Th-230 ages with the growth-band ages showed that the Th-230 ages were accurate within an error of + or - 3-5 y. Th-230 dates were then determined for two adjacent emerged heads from Santo Island; the dates were the same, indicating that the heads died at the same time, and consistent with the theory that they were killed by coseismic emergence around 1865 AD. The difference between this data and the data of the only major historically documented earthquake that caused an uplift (1973) suggests a seismic recurrence interval of 108 + or - 4 y for Santo. It is suggested that this approach may be extended back in time and to other localities.

  8. Paternal-age effects on sperm aneuploidy investigated in mice and humans by three-chromosome fluorescence in situ hybridization

    SciTech Connect

    Wyrobek, A.J.; Lowe, X.; Holland, N.T.

    1994-09-01

    We conducted a cross-species comparison of the effects of paternal age on sperm aneuploidy in mice and humans. A new murine assay was developed to detect sperm hyperhaploidy and polyploidy for chromosomes X, Y, and 8 using fluorescence in situ hybridization with chromosome-specific DNA probes, to serve as a direct corollate to the three-chromosome method developed early for human sperm. Sperm aneuploidy was evaluated in eight male B6C3F1 male mice (aged 22.5-30.5 mo) and compared to young controls (2.4 mo). The aged group showed significant ({approximately}2.0-fold) increases in hyperhaploidies involving chromosomes X, Y and 8, with the greatest effects seen in the oldest animals. Sperm aneuploidy was also evaluated in two groups of healthy men who differed in mean age [46.8{plus_minus}3.1 (n=4) vs. 28.5{plus_minus}5.0 (n=10) yrs], using the three-chromosome method. The older group showed a statistically significant increase in hyperhaploid sperm for both sex chromosomes. Additional controlled human studies are planned. Taken together, the murine and human data are consistent with a positive effect of paternal age on sperm aneuploidy. In both species, the strongest age effect was observed for hyperhaploidies of chromosome Y. Future studies are needed to investigate the shape of the age-effect curve and to evaluate chromosomal differences, especially for humans in their late reproductive years.

  9. Aging and Aged in Organized Crime.

    ERIC Educational Resources Information Center

    Amir, Menachem

    1989-01-01

    Examines problems of the aged in organized crime, basing discussion on organized crime bosses over age 60 operating in Italy, the United States, and Israel. Looks at problems stemming from normative system in organized crime, role of the aged, intergenerational problems, fears of the aged, excuses and justifications, standards of life, and…

  10. Oral Health and Aging

    MedlinePlus

    ... please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Summer 2016 Table of Contents Jerrold H. Epstein, ... they may need. Read More "Oral Health and Aging" Articles Oral Health and Aging / 4 Myths About ...

  11. What's Your Aging IQ?

    MedlinePlus

    ... Home » What's Your Aging IQ? Heath and Aging What's Your Aging IQ? About this booklet We all know someone " ... at the dry cleaners. But what is normal aging? In this booklet there are several very short ...

  12. The Biology of Aging.

    ERIC Educational Resources Information Center

    Sprott, Richard L.; And Others

    1992-01-01

    Thirteen articles in this special issue discuss aging theories, biomarkers of aging, aging research, disease, cancer biology, Alzheimer's disease, stress, oxidation of proteins, gene therapy, service delivery, biogerontology, and ethics and aging research. (SK)

  13. Increased ADAMTS1 mediates SPARC-dependent collagen deposition in the aging myocardium.

    PubMed

    Toba, Hiroe; de Castro Brás, Lisandra E; Baicu, Catalin F; Zile, Michael R; Lindsey, Merry L; Bradshaw, Amy D

    2016-06-01

    Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein highly expressed during fibrosis. Fibrosis is a prominent component of cardiac aging that reduces myocardial elasticity. Previously, we reported that SPARC deletion attenuated myocardial stiffness and collagen deposition in aged mice. To investigate the mechanisms by which SPARC promotes age-related cardiac fibrosis, we evaluated six groups of mice (n = 5-6/group): young (3-5 mo old), middle-aged (10-12 mo old), and old (18-29 mo old) C57BL/6 wild type (WT) and SPARC-null (Null) mice. Collagen content, determined by picrosirius red staining, increased in an age-dependent manner in WT but not in Null mice. A disintegrin and metalloproteinase with thrombospondin-like motifs 1 (ADAMTS1) increased in middle-aged and old WT compared with young, whereas in Null mice only old animals showed increased ADAMTS1 expression. Versican, a substrate of ADAMTS1, decreased with age only in WT. To assess the mechanisms of SPARC-induced collagen deposition, we stimulated cardiac fibroblasts with SPARC. SPARC treatment increased secretion of collagen I and ADAMTS1 (both the 110-kDa latent and 87-kDa active forms) into the conditioned media as well as the cellular expression of transforming growth factor-β1-induced protein (Tgfbi) and phosphorylated Smad2. An ADAMTS1 blocking antibody suppressed the SPARC-induced collagen I secretion, indicating that SPARC promoted collagen production directly through ADAMTS1 interaction. In conclusion, ADAMTS1 is an important mediator of SPARC-regulated cardiac aging. PMID:27143554

  14. Arsenic trioxide (As{sub 2}O{sub 3}) induced calcium signals and cytotoxicity in two human cell lines: SY-5Y neuroblastoma and 293 embryonic kidney (HEK)

    SciTech Connect

    Florea, Ana-Maria; Splettstoesser, Frank; Buesselberg, Dietrich . E-mail: Dietrich.Buesselberg@uni-due.de

    2007-05-01

    Arsenic trioxide (As{sub 2}O{sub 3}) has anticancer properties; however, its use also leads to neuro-, hepato- or nephro-toxicity, and therefore, it is important to understand the mechanism of As{sub 2}O{sub 3} toxicity. We studied As{sub 2}O{sub 3} influence on intracellular calcium ([Ca{sup 2+}]{sub i}) homeostasis of human neuroblastoma SY-5Y and embryonic kidney cells (HEK 293).We also relate the As{sub 2}O{sub 3} induced [Ca{sup 2+}]{sub i} modifications with cytotoxicity. We used Ca{sup 2+} sensitive dyes (fluo-4 and rhod-2) combined with laser scanning microscopy or fluorescence activated cell sorting to measure Ca{sup 2+} changes during the application of As{sub 2}O{sub 3} and we approach evaluation of cytotoxicity. As{sub 2}O{sub 3} (1 {mu}M) increased [Ca{sup 2+}]{sub i} in SY-5Y and HEK 293 cells. Three forms of [Ca{sup 2+}]{sub i}-elevations were found: (1) steady-state increases (2) transient [Ca{sup 2+}]{sub i}-elevations and (3) Ca{sup 2+}-spikes. [Ca{sup 2+}]{sub i} modifications were independent from extracellular Ca{sup 2+} but dependent on internal calcium stores. The effect was not reversible. Inositol triphosphate (IP{sub 3}) and ryanodine (Ry) receptors are involved in regulation of signals induced by As{sub 2}O{sub 3}. 2-APB and dantrolene significantly reduced the [Ca{sup 2+}]{sub i}-rise (p < 0.001, t-test) but did not completely abolish [Ca{sup 2+}]{sub i}-elevation or spiking. This indicates that other Ca{sup 2+} regulating mechanisms are involved. In cytotoxicity tests As{sub 2}O{sub 3} significantly reduced cell viability in both cell types. Staining with Hoechst 33342 showed occurrence of apoptosis and DNA damage. Our data suggest that [Ca{sup 2+}]{sub i} is an important messenger in As{sub 2}O{sub 3} induced cell death.

  15. Anti-autophagic and anti-apoptotic effects of memantine in a SH-SY5Y cell model of Alzheimer's disease via mammalian target of rapamycin-dependent and -independent pathways

    PubMed Central

    SONG, GUIJUN; LI, YU; LIN, LULU; CAO, YUNPENG

    2015-01-01

    Memantine non-competitively blocks the N-methyl-d-aspartate receptor in order to inhibit beta-amyloid (Aβ) secretion, and has been used to treat moderate-to-severe Alzheimer's disease (AD). However, the mechanisms underlying the role of memantine in the autophagy and apoptosis of neuronal cells in AD, as well as the association between neuronal autophagy and apoptosis have yet to be elucidated. The present study aimed to establish an AD cell model overexpressing the 695-amino-acid Swedish mutant of Aβ precursor protein (APP695swe) in order to observe the effects of memantine on the cell viability, autophagy and apoptosis of SH-SY5Y cells in the AD model, and to investigate the associated underlying mechanisms. A pcDNA3.1-APP695 plasmid was transfected into the SH-SY5Y cells. Reverse transcription-quantitative polymerase chain reaction and western blot analyses demonstrated that the AD cell model was successfully established. MTT assays demonstrated that memantine was able to upregulate neuronal cell survival, and acridine orange staining and flow cytometry demonstrated that memantine (5 µM) was able to inhibit neuronal autophagy and apoptosis. Following neuronal autophagy induction by rapamycin, cell apoptosis rates increased significantly. Further experiments revealed that memantine was able to upregulate the expression of signaling molecules phosphorylated (p)-phosphoinositide 3-kinase, p-Akt and p-mammalian target of rapamycin (mTOR), and also inhibited the phosphorylation of the B-cell lymphoma 2/Beclin-1 complex via mitogen-activated protein kinase 8. In conclusion, the results of the present study demonstrated that in the AD cell model, autophagy was able to promote apoptosis. Memantine exerted anti-autophagic and anti-apoptotic functions, and mTOR-dependent as well as-independent autophagic signaling pathways were involved in this process. Therefore, these results of the present study strongly supported the use of memantine as a potential therapeutic

  16. Hydrodynamic Qualities of a 1/10-Size Powered Dynamic Model of the XP5Y-1 Flying Boat in Smooth Water: Langley Tank Model 246, TED No. NACA DE 320

    NASA Technical Reports Server (NTRS)

    Woodward, David R.; Weinstein, Irving; Whitaker, Walter E., Jr.

    1947-01-01

    The hydrodynamic characteristics of a 1/10-size powered dynamic model of the XP5Y-1 flying boat were determined in Langley tank no. 1. Stable take-offs were possible at all practicable positions of the center of gravity and flap deflections. An increase in gross load from 123.5 to 150.0 pounds (21.5 percent) had only a slight effect on the stable range for take-off. A decrease in forward acceleration from 3.0 to 1.0 feet per second per second had only a very small effect on the stable range for take-off. In general, the landings were free from skipping except at trims below 6 deg where one skip was encountered at an aft position of the center of gravity. The model porpoised during the landing runout at all positions of the center of gravity when landed at trims above 10 deg. Spray in the propellers was light at the design gross load, and was not considered excessive,at a gross load of 136.0 pounds.

  17. Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways.

    PubMed

    Yuan, Ding; Wan, Jing-Zhi; Deng, Li-Li; Zhang, Chang-Cheng; Dun, Yao-Yan; Dai, Yan-Wen; Zhou, Zhi-Yong; Liu, Chao-Qi; Wang, Ting

    2014-01-01

    Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects. PMID:25073091

  18. Protection against MPP(+)-induced neurotoxicity in SH-SY5Y cells by tormentic acid via the activation of PI3-K/Akt/GSK3β pathway.

    PubMed

    Zhao, Qing; Ye, Junli; Wei, Na; Fong, Chichun; Dong, Xiaoli

    2016-07-01

    The cause of Parkinson's disease (PD) could be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of tormentic acid (TA), a naturally occurring triterpene extracted from medicinal plants such as Rosa rugosa and Potentilla chinensis, were evaluated in a widely used cellular PD model in which neurotoxicity was induced by MPP(+) in cultured SH-SY5Y cells. We found that TA at 1-30 μM substantially protected against MPP(+)-induced neurotoxicity, as evidenced by the increase in cell viability, decrease in lactate dehydrogenase release and the reduction in apoptotic nuclei. Moreover, TA effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as Bax/Bcl-2 ratio caused by MPP(+). Most importantly, TA markedly reversed the inhibition of protein expression of phosphorylated Akt (Ser 473) and phosphorylated GSK3β (Ser 9) caused by MPP(+). LY294002, the specific inhibitor of PI3-K, significantly abrogated the up-regulated phosphorylated Akt and phosphorylated GSK3β offered by TA, suggesting that the neuroprotection of TA was mainly dependent on the activation of PI3-K/Akt/GSK3β signaling pathway. The results taken together indicate that TA may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. PMID:26994872

  19. Melatonin prevents cytosolic calcium overload, mitochondrial damage and cell death due to toxically high doses of dexamethasone-induced oxidative stress in human neuroblastoma SH-SY5Y cells.

    PubMed

    Suwanjang, Wilasinee; Abramov, Andrey Y; Charngkaew, Komgrid; Govitrapong, Piyarat; Chetsawang, Banthit

    2016-07-01

    Stressor exposure activates the hypothalamic-pituitary-adrenal (HPA) axis and causes elevations in the levels of glucocorticoids (GC) from the adrenal glands. Increasing evidence has demonstrated that prolonged exposure to high GC levels can lead to oxidative stress, calcium deregulation, mitochondrial dysfunction and apoptosis in a number of cell types. However, melatonin, via its antioxidant activity, exhibits a neuroprotective effect against oxidative stress-induced cell death. Therefore, in the present study, we explored the protective effect of melatonin in GC-induced toxicity in human neuroblastoma SH-SY5Y cells. Cellular treatment with the toxically high doses of the synthetic GC receptor agonist, dexamethasone (DEX) elicited marked decreases in the levels of glutathione and increases in ROS production, lipid peroxidation and cell death. DEX toxicity also induced increases in the levels of cytosolic calcium and mitochondrial fusion proteins (Mfn1 and Opa1) but decreases in the levels of mitochondrial fission proteins (Fis1 and Drp1). Mitochondrial damage was observed in large proportions of the DEX-treated cells. Pretreatment of the cells with melatonin substantially prevented the DEX-induced toxicity. These results suggest that melatonin might exert protective effects against oxidative stress, cytosolic calcium overload and mitochondrial damage in DEX-induced neurotoxicity. PMID:27155536

  20. Valence Fluctuations Revealed by Magnetic Field and Pressure Scans: Comparison with Experiments in YbXCu4 (X=In, Ag, Cd) and CeYIn5 (Y=Ir, Rh)

    NASA Astrophysics Data System (ADS)

    Watanabe, Shinji; Tsuruta, Atsushi; Miyake, Kazumasa; Flouquet, Jacques

    2009-10-01

    The mechanism of how critical end points of the first-order valence transition (FOVT) are controlled by a magnetic field is discussed. We demonstrate that critical temperature is suppressed to be a quantum critical point (QCP) by a magnetic field. This results explain the field dependence of the isostructural FOVT observed in Ce metal and YbInCu4. Magnetic field scan can make the system reenter in a critical valence fluctuation region. Even in intermediate-valence materials, the QCP is induced by applying a magnetic field, at which magnetic susceptibility also diverges. The driving force of the field-induced QCP is shown to be a cooperative phenomenon of the Zeeman effect and the Kondo effect, which creates a distinct energy scale from the Kondo temperature. The key concept is that the closeness to the QCP of the FOVT is vital in understanding Ce- and Yb-based heavy-fermions. This explains the peculiar magnetic and transport responses in CeYIn5 (Y=Ir, Rh) and metamagnetic transition in YbXCu4 for X=In as well as the sharp contrast between X=Ag and Cd.

  1. An apolar Pistacia lentiscus L. leaf extract: GC-MS metabolic profiling and evaluation of cytotoxicity and apoptosis inducing effects on SH-SY5Y and SK-N-BE(2)C cell lines.

    PubMed

    Piccolella, Simona; Nocera, Paola; Carillo, Petronia; Woodrow, Pasqualina; Greco, Vincenza; Manti, Lorenzo; Fiorentino, Antonio; Pacifico, Severina

    2016-09-01

    In the course of a cytotoxicity screening of Mediterranean plants vs. neuroblastoma cells, Pistacia lentiscus was of interest. Pl-C extract, prepared from dried leaves by ultrasound assisted maceration (UAM) in chloroform, was profiled through using GC-MS techniques. To evaluate Pl-C cytotoxicity towards SH-SY5Y and SK-N-BE(2)-C cell lines, MTT, SRB and LDH assays were performed. The caspase-3 activation, DNA fragmentation, as well as micronucleation, were also evaluated. The Pl-C oxidant/antioxidant ability was estimated using different methods. The extract, rich in pentacyclic triterpenes, inhibited mitochondrial redox activity and cell viability of the tested cell lines. LDH assay established that Pl-C did not affect the cell membrane integrity. Indeed, it was able to activate caspase-3 and to cause a ladder pattern of DNA. Western blotting analysis showed that Pl-C processed caspase-3 providing two cleavage products of approximately 20 and 17-kDa, whose densitometric evaluation highlighted that Pl-C was more effective than vinblastine by 3-fold. The pro-apoptotic effect could be related to a disturbance in cell redox balance. In fact, it increased intracellular ROS production, GSSG/GSH ratio and the formation of lipoperoxidation products. The data obtained prompted to further investigate and assess the in vivo efficacy of Pl-C to prevent and/or treat neuroblastoma. PMID:27375189

  2. Cholesterol overload induces apoptosis in SH-SY5Y human neuroblastoma cells through the up regulation of flotillin-2 in the lipid raft and the activation of BDNF/Trkb signaling.

    PubMed

    Huang, Yen-Ning; Lin, Ching-I; Liao, Hsiang; Liu, Chin-Yu; Chen, Yue-Hua; Chiu, Wan-Chun; Lin, Shyh-Hsiang

    2016-07-22

    Epidemiological investigations have shown that Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. It has been indicated that the cholesterol concentration in the brain of AD patients is higher than that in normal people. In this study, we investigated the effects of cholesterol concentrations, 0, as the control, 3.125, 12.5, and 25μM, on cholesterol metabolism, neuron survival, AD-related protein expressions, and cell morphology and apoptosis using SH-SY5Y human neuroblastoma cells. We observed that expressions of cholesterol hydroxylase (Cyp46), flotillin-2 (a marker of lipid raft content), and truncated tyrosine kinase B (TrkBtc) increased, while expressions of brain-derived neurotrophic factor (BDNF) and full-length TrkB (TrkBfl) decreased as the concentration of cholesterol loading increased. Down-regulation of the PI3K-Akt-glycogen synthase kinase (GSK)-3β cascade and cell apoptosis were also observed at higher concentrations of cholesterol, along with elevated levels of β-amyloid (Aβ), β-secretase (BACE), and reactive oxygen species (ROS). In conclusion, we found that cholesterol overload in neuronal cells imbalanced the cholesterol homeostasis and increased the protein expressions causing cell apoptosis, which illustrates the neurodegenerative pathology of abnormally elevated cholesterol concentrations found in AD patients. PMID:27155148

  3. Chikusetsu saponin V attenuates H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells through Sirt1/PGC-1α/Mn-SOD signaling pathways.

    PubMed

    Wan, Jingzhi; Deng, Lili; Zhang, Changcheng; Yuan, Qin; Liu, Jing; Dun, Yaoyan; Zhou, Zhiyong; Zhao, Haixia; Liu, Chaoqi; Yuan, Ding; Wang, Ting

    2016-09-01

    Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Chikusetsu saponin V (CsV), the most abundant member of saponins from Panax japonicus (SPJ), has attracted increasing attention for its potential to treat neurodegenerative diseases. However, the mechanisms are unclear. Our study intended to investigate the antioxidative effects of CsV in human neuroblastoma SH-SY5Y cells. Our data showed that CsV attenuated H2O2-induced cytotoxicity, inhibited ROS accumulation, increased the activities of superoxide dismutase (SOD) and GSH, and increased mitochondrial membrane potential dose-dependently. Further exploration of the mechanisms showed that CsV exhibited these effects through increasing the activation of oxidative-stress-associated factors including Sirt1, PGC-1α, and Mn-SOD. Moreover, CsV inhibited H2O2-induced down-regulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. In conclusion, our study demonstrated that CsV exhibited neuroprotective effects possibly through Sirt1/PGC-1α/Mn-SOD signaling pathways. PMID:27332950

  4. Treatment with the neurotoxic Aβ (25-35) peptide modulates the expression of neuroprotective factors Pin1, Sirtuin 1, and brain-derived neurotrophic factor in SH-SY5Y human neuroblastoma cells.

    PubMed

    Lattanzio, Francesca; Carboni, Lucia; Carretta, Donatella; Candeletti, Sanzio; Romualdi, Patrizia

    2016-05-01

    The deposition of Amyloid β peptide plaques is a pathological hallmark of Alzheimer's disease (AD). The Aβ (25-35) peptide is regarded as the toxic fragment of full-length Aβ (1-42). The mechanism of its toxicity is not completely understood, along with its contribution to AD pathological processes. The aim of this study was to investigate the effect of the neurotoxic Aβ (25-35) peptide on the expression of the neuroprotective factors Pin1, Sirtuin1, and Bdnf in human neuroblastoma cells. Levels of Pin1, Sirtuin 1, and Bdnf were compared by real-time PCR and Western blotting in SH-SY5Y cells treated with Aβ (25-35) or administration vehicle. The level of Pin1 gene and protein expression was significantly decreased in cells exposed to 25μM Aβ (25-35) compared to vehicle-treated controls. Similarly, Sirtuin1 expression was significantly reduced by Aβ (25-35) exposure. In contrast, both Bdnf mRNA and protein levels were significantly increased by Aβ (25-35) treatment, suggesting the activation of a compensatory response to the insult. Both Pin1 and Sirtuin 1 exert a protective role by reducing the probability of plaque deposition, since they promote amyloid precursor protein processing through non-amyloidogenic pathways. The present results show that Aβ (25-35) peptide reduced the production of these neuroprotective proteins, thus further increasing Aβ generation. PMID:26915812

  5. Avoiding Aging? Social Psychology's Treatment of Age

    ERIC Educational Resources Information Center

    Barrett, Anne E.; Redmond, Rebecca; von Rohr, Carmen

    2012-01-01

    Population aging, in conjunction with social and cultural transformations of the life course, has profound implications for social systems--from large-scale structures to micro-level processes. However, much of sociology remains fairly quiet on issues of age and aging, including the subfield of social psychology that could illuminate the impact of…

  6. Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders.

    PubMed

    Koutsouleris, Nikolaos; Davatzikos, Christos; Borgwardt, Stefan; Gaser, Christian; Bottlender, Ronald; Frodl, Thomas; Falkai, Peter; Riecher-Rössler, Anita; Möller, Hans-Jürgen; Reiser, Maximilian; Pantelis, Christos; Meisenzahl, Eva

    2014-09-01

    Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders. PMID:24126515

  7. Exercise and age

    MedlinePlus

    Age and exercise ... It is never too late to start exercising. Exercise has benefits at any age. Don't worry ... as you age. The right kind of regular exercise can also reduce your risk of heart disease, ...

  8. Administration on Aging

    MedlinePlus

    ... Back to top Older Americans Act and Aging Network To meet the diverse needs of the growing ... the OAA, and a link to National Aging Network information (State Units on Aging and Area Agencies ...

  9. Skin Care and Aging

    MedlinePlus

    ... Age Spots and Skin Tags Click for more information Age spots, once called "liver spots," are flat, brown ... surface. They are a common occurrence as people age, especially for women. They are ... options, specific conditions, and related issues. ...

  10. Neuroprotective effect of sulfated polysaccharide isolated from sea cucumber Stichopus japonicus on 6-OHDA-induced death in SH-SY5Y through inhibition of MAPK and NF-κB and activation of PI3K/Akt signaling pathways.

    PubMed

    Cui, Chao; Cui, Ningshan; Wang, Peng; Song, Shuliang; Liang, Hao; Ji, Aiguo

    2016-02-01

    The purpose of this study is to investigate the protective effect and molecular mechanism of the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus against 6-OHDA-induced toxicity in SH-SY5Y cells. The results showed that SJP could protect SH-SY5Y cells against 6-OHDA-induced cell injury. We found that SJP effectively improves cell viability, decreases LDH leakage, and reverses morphological damage. Moreover, SJP significantly increases SOD activity but decreases MDA levels and ROS generation. Effect of SJP on 6-OHDA-induced cell death in SH-SY5Y cells is associated with an arrest in the G1/S phase of the cell cycle and inhibits the expression of Cyclin D3. 6-OHDA-induced intracellular generation of ROS and mitochondrial dysfunctions, release of cytochrome c, imbalance of Bax/Bcl-2, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 ratio, and p-p53 activation were strikingly attenuated by SJP pretreatment. Meanwhile, SJP counteracted NF-κB activation, thereby preventing up-regulation of iNOS and intracellular NO release. The data provide the first evidence that SJP protects SH-SY5Y cells against 6-OHDA toxicity possibly by inhibiting MAPK and NF-κB and activating PI3K/Akt signaling pathways. Thus, SJP is a candidate for further evaluation of its protective effects against neurodegeneration in PD. PMID:26773499

  11. Nutrients, Microglia Aging, and Brain Aging

    PubMed Central

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging. PMID:26941889

  12. Controlled synthesis and luminescence properties of Ca0.5Y1-x(MoO4)2:xRE3+ (RE = Eu, Pr, Sm, Tb, Dy, Yb/Er, Yb/Tm, and Yb/Ho) phosphors by hydrothermal method versus pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Mahalingam, Venkatakrishnan; Thirumalai, Jagannathan; Krishnan, Rajagopalan; Chandramohan, Rathinam

    2016-01-01

    Herein, we report on rare-earth (RE) activated Ca0.5Y1-x(MoO4)2:xRE3+ (RE = Eu, Pr, Sm, Tb, Dy, Yb/Er, Yb/Ho, and Yb/Tm) phosphors synthesized using a surfactant-mediated hydrothermal route. Timedependent experiments were performed, and the morphological evolution of the phosphors was studied. From prepared powder samples of Ca0.5Y1-x(MoO4)2:xRE3+ (RE = Eu and Yb/Er), nano-sized thin phosphor films were grown using pulsed laser deposition (PLD). The surface topography of the as-grown thin phosphor films was analyzed. The asprepared phosphors were characterized by structural and optical studies. The powder phosphor exhibited bi pyramid-like micro-architectures. Structural studies indicated that Ca0.5Y1-x(MoO4)2 possesses the scheelite tetragonal crystal structure. The down-conversion luminescence of Ca0.5Y1-x(MoO4)2:xRE3+ (RE = Eu, Pr, Sm, Tb, and Dy) as powder phosphors and Eu3+ doped Ca0.5Y1-x(MoO4)2 thin phosphor film were studied. Upon irradiation with a 980 nm laser, the Ca0.5Y1-x(MoO4)2: xRE3+ (RE = Yb/Er, Yb/Ho, and Yb/Tm) powder phosphors and Ca0.5Y1-x(MoO4)2:xRE3+ (RE = Yb/Er) thin phosphor film showed intense up-converted visible emissions in green, yellow, and blue regions. The fluorescence decay time and color co-ordinates were determined for all synthesized phosphors. From the obtained results, the prepared powder and thin film phosphors are suggested to be suitable candidates for display and electro-luminescence applications. [Figure not available: see fulltext.

  13. MARK-AGE biomarkers of ageing.

    PubMed

    Bürkle, Alexander; Moreno-Villanueva, María; Bernhard, Jürgen; Blasco, María; Zondag, Gerben; Hoeijmakers, Jan H J; Toussaint, Olivier; Grubeck-Loebenstein, Beatrix; Mocchegiani, Eugenio; Collino, Sebastiano; Gonos, Efstathios S; Sikora, Ewa; Gradinaru, Daniela; Dollé, Martijn; Salmon, Michel; Kristensen, Peter; Griffiths, Helen R; Libert, Claude; Grune, Tilman; Breusing, Nicolle; Simm, Andreas; Franceschi, Claudio; Capri, Miriam; Talbot, Duncan; Caiafa, Paola; Friguet, Bertrand; Slagboom, P Eline; Hervonen, Antti; Hurme, Mikko; Aspinall, Richard

    2015-11-01

    Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation. PMID:25818235

  14. The preparation of high-J c Gd0.5Y0.5Ba2Cu3O7‑δ thin films by the MOCVD process

    NASA Astrophysics Data System (ADS)

    Zhao, R. P.; Zhang, F.; Liu, Q.; Xia, Y. D.; Lu, Y. M.; Cai, C. B.; Tao, B. W.; Li, Y. R.

    2016-06-01

    A home-designed metal organic chemical vapor deposition (MOCVD) system has been employed to prepare high critical current density (J c) Gd0.5Y0.5Ba2Cu3O7‑δ (GdYBCO) thin films on LaMnO3/epitaxial MgO/ion beam assisted deposition (IBAD)-MgO/solution deposition planarization (SDP)-Y2O3-buffered Hastelloy tapes; the thin films were directly heated by the Joule effect after applying an heating current (I h ) through the Hastelloy tapes. The effect of the mole ratio of the metal organic sources has been systematically investigated. X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses indicated that the GdYBCO films crystallized better and became denser with the increasing of the Cu/Ba ratio from 1.0 to 1.1, yielding a J c at 77 K and 0 T of 200 nm GdYBCO film increasing from 2.5 MA cm‑2 to 7 MA cm‑2. In addition, SEM and energy dispersive spectrometer (EDS) characterizations revealed that more and more outgrowths appeared and the density of the film was reduced with an increase in the Cu/Ba ratio from 1.1 to 1.2. When the I h was 26.8 A and the mole ratio of Gd(tmhd)3, Y(tmhd)3, Ba(tmhd)2 and Cu(tmhd)2 in the precursor was 0.55:0.55:2:2.2, the critical current (I c) of the deposited 200 nm-thick GdYBCO film reached a 140 A cm‑1 width (77 K, 0 T), corresponding to the J c 7 MA cm‑2 (77 K, 0 T).

  15. Mitogen-activated protein kinases regulate expression of neuronal nitric oxide synthase and neurite outgrowth via non-classical retinoic acid receptor signaling in human neuroblastoma SH-SY5Y cells.

    PubMed

    Fujibayashi, Tatsuya; Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro; Shudo, Koichi; Katsuki, Hiroshi

    2015-10-01

    We have previously shown that retinoic acid receptor (RAR) stimulation by an agonist Am80 recruits nitric oxide-dependent signaling via increased expression of neuronal nitric oxide synthase (nNOS) in rat midbrain slice cultures. Using neuroblastoma SH-SY5Y cells, here we investigated the mechanisms of RAR-induced nNOS expression, together with relationship between nNOS expression and neurite outgrowth. Am80 promoted neurite outgrowth, which was attenuated by inhibitors of phosphoinositide 3-kinase (PI3K; LY294002), c-Jun N-terminal kinase (JNK; SP600125) and p38 mitogen-activated protein kinase (p38 MAPK; SB203580). A selective nNOS inhibitor 3-bromo-nitroindazole also suppressed Am80-induced neurite outgrowth. Am80-induced increase in nNOS protein expression was attenuated by LY294002, SP600125 and SB203580, whereas increase in nNOS mRNA expression was attenuated only by LY294002. Am80-induced activation of JNK and p38 MAPK was blocked by LY294002, suggesting that these kinases acted downstream of PI3K. We also confirmed that DAX1, a nuclear receptor reported to regulate nNOS expression, was up-regulated in response to Am80. siRNA-mediated knockdown of DAX1 abrogated Am80-induced nNOS expression and neurite outgrowth. These results reveal for the first time that nNOS expression is crucial for RAR-mediated neurite outgrowth, and that non-genomic signaling such as JNK and p38 MAPK is involved in RAR-mediated nNOS expression. PMID:26422672

  16. Protection against 1-methyl-4-phenyl pyridinium-induced neurotoxicity in human neuroblastoma SH-SY5Y cells by Soyasaponin I by the activation of the phosphoinositide 3-kinase/AKT/GSK3β pathway.

    PubMed

    Guo, Zheng; Cao, Wei; Zhao, Shifeng; Han, Zengtai; Han, Boxiang

    2016-07-01

    Parkinson's disease (PD) can be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of Soyasaponin I (Soya-I), a naturally occurring triterpene extracted from a widely used ingredient in many foods, such as Glycine max (soybean), were evaluated in a widely used cellular PD model in which neurotoxicity was induced by 1-methyl-4-phenyl pyridinium (MPP) in cultured SH-SY5Y cells. We found that Soya-I at 10-40 μM considerably protected against MPP-induced neurotoxicity as evidenced by an increase in cell viability, a decrease in lactate dehydrogenase release, and a reduction in apoptotic nuclei. Moreover, Soya-I effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as the Bax/Bcl-2 ratio caused by MPP. Most importantly, Soya-I markedly reversed the inhibition of protein expression of phosphorylated AKT and phosphorylated GSK3β caused by MPP. LY294002, the specific inhibitor of phosphoinositide 3-kinase, significantly abrogated the upregulated phosphorylated AKT and phosphorylated GSK3β offered by Soya-I, suggesting that the neuroprotection of Soya-I was mainly dependent on the activation of the phosphoinositide 3-kinase/AKT/GSK3β signaling pathway. The results taken together indicate that Soya-I may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. PMID:27196724

  17. Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death

    SciTech Connect

    Guida, Natascia; Laudati, Giusy; Galgani, Mario; Santopaolo, Marianna; Montuori, Paolo; Triassi, Maria; Di Renzo, Gianfranco; Canzoniero, Lorella M.T.; Formisano, Luigi

    2014-10-01

    Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1–100 μM) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. - Highlights: • Di(2-ethylhexyl)phthalate (DEHP) is cytotoxic to SH-SY5Y cells and cortical neurons. • DEHP-induced cytotoxicity is mediated by apoptosis. • DEHP-induced apoptotic cell death is inhibited by class II HDAC MC-1568. • DEHP neurotoxicity is caused by HDAC4-mediated Sp3 degradation by ubiquitin.

  18. Long-term morphine treatment enhances proteasome-dependent degradation of G beta in human neuroblastoma SH-SY5Y cells: correlation with onset of adenylate cyclase sensitization.

    PubMed

    Moulédous, Lionel; Neasta, Jérémie; Uttenweiler-Joseph, Sandrine; Stella, Alexandre; Matondo, Mariette; Corbani, Maïthé; Monsarrat, Bernard; Meunier, Jean-Claude

    2005-08-01

    The initial aim of this study was to identify protein changes associated with long-term morphine treatment in a recombinant human neuroblastoma SH-SY5Y clone (sc2) stably overexpressing the human mu-opioid (MOP) receptor. In MOP receptor-overexpressing sc2 cells, short-term morphine exposure was found to be much more potent and efficacious in inhibiting forskolin-elicited production of cAMP, and long-term morphine exposure was shown to induce a substantially higher degree of opiate dependence, as reflected by adenylate cyclase sensitization, than it did in wild-type neuroblastoma cells. Differential proteomic analysis of detergent-resistant membrane rafts isolated from untreated and chronically morphine-treated sc2 cells revealed long-term morphine exposure to have reliably induced a 30 to 40% decrease in the abundance of five proteins, subsequently identified by mass spectrometry as G protein subunits alphai(2), alphai(3), beta(1), and beta(2), and prohibitin. Quantitative Western blot analyses of whole-cell extracts showed that long-term morphine treatment-induced down-regulation of Gbeta but not of the other proteins is highly correlated (r(2) = 0.96) with sensitization of adenylate cyclase. Down-regulation of Gbeta and adenylate cyclase sensitization elicited by long-term morphine treatment were suppressed in the presence of carbobenzoxy-l-leucyl-l-leucyl-l-norvalinal (MG-115) or lactacystin. Thus, sustained activation of the MOP receptor by morphine in sc2 cells seems to promote proteasomal degradation of Gbeta to sensitize adenylate cyclase. Together, our data suggest that the long-term administration of opiates may elicit dependence by altering the neuronal balance of heterotrimeric G proteins and adenylate cyclases, with the ubiquitin-proteasome pathway playing a pivotal role. PMID:15901846

  19. Capacitative Ca2+ entry is involved in regulating soluble amyloid precursor protein (sAPPalpha) release mediated by muscarinic acetylcholine receptor activation in neuroblastoma SH-SY5Y cells.

    PubMed

    Kim, Jin Hyoung; Choi, Sinkyu; Jung, Ji-Eun; Roh, Eun-Jihn; Kim, Hwa-Jung

    2006-04-01

    Previous studies have demonstrated that stimulation of phospholipase C-linked G-protein-coupled receptors, including muscarinic M1 and M3 receptors, increases the release of the soluble form of amyloid precursor protein (sAPPalpha) by alpha-secretase cleavage. In this study, we examined the involvement of capacitative Ca2+ entry (CCE) in the regulation of muscarinic acetylcholine receptor (mAChR)-dependent sAPPalpha release in neuroblastoma SH-SY5Y cells expressing abundant M3 mAChRs. The sAPPalpha release stimulated by mAChR activation was abolished by EGTA, an extracellular Ca2+ chelator, which abolished mAChR-mediated Ca2+ influx without affecting Ca2+ mobilization from intracellular stores. However, mAChR-mediated sAPPalpha release was not inhibited by thapsigargin, which increases basal [Ca2+]i by depletion of Ca2+ from intracellular stores. While these results indicate that the mAChR-mediated increase in sAPPalpha release is regulated largely by Ca2+ influx rather than by Ca2+ mobilization from intracellular stores, we further investigated the Ca2+ entry mechanisms regulating this phenomenon. CCE inhibitors such as Gd3+, SKF96365, and 2-aminoethoxydiphenyl borane (2-APB), dose dependently reduced both Ca2+ influx and sAPPalpha release stimulated by mAChR activation, whereas inhibition of voltage-dependent Ca2+ channels, Na+/Ca2+ exchangers, or Na+-pumps was without effect. These results indicate that CCE plays an important role in the mAChR-mediated release of sAPPalpha. PMID:16524374

  20. Muscarine enhances soluble amyloid precursor protein secretion in human neuroblastoma SH-SY5Y by a pathway dependent on protein kinase C(alpha), src-tyrosine kinase and extracellular signal-regulated kinase but not phospholipase C.

    PubMed

    Canet-Aviles, Rosa-Maria; Anderton, Mark; Hooper, Nigel M; Turner, Anthony J; Vaughan, Peter F T

    2002-06-15

    The signalling pathways by which muscarine and epidermal growth factor (EGF) regulate the secretion of the alpha-secretase cleavage product (sAPPalpha) of the amyloid precursor protein (APP) were examined in the human neuroblastoma SH-SY5Y. Using specific inhibitors it was found that over 80% of sAPPalpha secretion, enhanced by muscarine, occurred via the extracellular signal-regulated kinase (ERK1/2) member of the mitogen-activated protein kinase (MAPK) family and was dependent on protein kinase Calpha (PKCalpha) and a member of the Src family of non-receptor tyrosine kinases (Src-TK). In contrast the stimulation of sAPPalpha secretion by EGF was not affected by inhibitors of PKC nor Src-TK but was dependent on ERK1/2. In addition muscarine-enhanced sAPPalpha secretion and ERK1/2 activation were inhibited 60 and 80%, respectively, by micromolar concentrations of the phosphatidylinositol 3 kinase (PI-3K) inhibitor wortmannin. In comparison wortmannin decreased EGF stimulation of sAPPalpha secretion and ERK 1/2 activation by approximately 40%. Unexpectedly, U73122, an inhibitor of phosphoinositide-specific phospholipase C, did not inhibit muscarine enhancement of sAPPalpha secretion. These data are discussed in relation to a pathway for the enhancement of sAPPalpha secretion by muscarine which involves the activation of a Src-TK by G-protein beta/gamma-subunits leading to activation of PKCalpha, and ERK1/2 by a mechanism not involving phospholipase C. PMID:12191495

  1. The link between mitochondrial complex I and brain-derived neurotrophic factor in SH-SY5Y cells--The potential of JNX1001 as a therapeutic agent.

    PubMed

    Kim, Helena K; Mendonça, Karina M; Howson, Patrick A; Brotchie, Jonathan M; Andreazza, Ana C

    2015-10-01

    Mitochondrial complex I, which is the first member of the electron transport chain responsible for producing ATP, can produce reactive oxygen species and oxidative stress when it becomes dysfunctional. Complex I dysfunction and oxidative stress are strongly implicated in bipolar disorder (BD), a debilitating psychiatric disease, as is decreased levels of brain derived neurotrophic factor (BDNF) found in patients with BD, which is related to complex I activity. JNX1001, a clinical trial ready brain penetrant sapogenin, increases BDNF levels in animal models. Hence, we aimed to examine if JNX1001 can prevent complex I dysfunction-induced alterations produced by rotenone treatment in human neuroblastoma cells (SH-SY5Y). Complex I dysfunction decreased cell viability and increased protein carbonylation and nitration, confirming previous findings. Complex I dysfunction also decreased intracellular and extracellular BDNF levels. JNX1001 pre-treatment prevented complex I dysfunction-induced protein carbonylation and nitration and improved cell viability at concentrations of 30 nM and 300 nM, but more robustly at 300 nM. JNX1001 was also able to prevent decreased intracellular and extracellular BDNF levels, where it produced a ten-fold increase in intracellular BDNF levels at a concentration of 300 nM. While further studies are required to examine the neuroprotective ability of JNX1001 against alterations produced by complex I defect in more complex systems, such as in animal models, the findings of this study demonstrate the potential of JNX1001 to be used as a therapeutic agent to protect against complex I dysfunction-induced alterations that may be highly relevant to BD. PMID:26164791

  2. Involvement of dopamine D(2)/D(3) receptors and BDNF in the neuroprotective effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in terminally differentiated SH-SY5Y cells.

    PubMed

    Presgraves, Steve P; Borwege, Sabine; Millan, Mark J; Joyce, Jeffrey N

    2004-11-01

    Anti-parkinsonian agents possessing both D(2) and D(3) receptor agonist properties are neuroprotective against 1-methyl-4-phenylpyridinium (MPP(+)) toxicity in a variety of in vitro models. The mechanisms underlying protection by these D(2)/D(3) receptor agonists remain poorly defined. To test if the D(3) receptor preferring agonists S32504 and pramipexole act through D(2) or D(3) receptors and via brain-derived neurotrophic factor (BDNF)-dependent pathways, we utilized a terminally differentiated neuroblastoma SH-SY5Y cell line exhibiting a dopaminergic phenotype. The cytotoxic effects of MPP(+) (LD(50) of 100 microM) were stereospecifically antagonized by S32504 (EC(50) = 2.0 microM) and, less potently, by pramipexole (EC(50) = 64.3 microM), but not by their inactive stereoisomers, R(+) pramipexole and S32601, respectively. Neuroprotective effects afforded by EC(50) doses of S32504 and pramipexole were antagonized by the selective D(3) antagonists S33084, U99194A, and SB269652, and by the D(2)/D(3) antagonist raclopride. However, the preferential D(2) receptor antagonist LY741626 was ineffective as was the D1 antagonist SCH23390. BDNF (1 nM) potently protected against MPP(+)-induced neurotoxicity. Antibody directed against BDNF concentration-dependently blocked both the neuroprotective effects of BDNF and those of pramipexole and S32504 against MPP(+). The protection afforded by BDNF was blocked by the P3K-AKT pathway inhibitor LY249002 and less so by the MEK/MAPKK pathway inhibitor PD98059. LY249002, but not PD98059, blocked the neuroprotective effects of pramipexole and S32504 against MPP(+) toxicity. In conclusion, S32504 and, less potently, pramipexole show robust, stereospecific, and long-lasting neuroprotective effects against MPP(+) toxicity that involve D(3) receptors. Their actions also reflect downstream recruitment of BDNF and via a PK3-AKT pathway. PMID:15473989

  3. Aging Periodontium, Aging Patient: Current Concepts.

    PubMed

    Ryder, Mark

    2015-08-01

    A functioning natural dentition is essential to maintaining overall health in the elderly patient. While age-related alterations in periodontal tissues and the immune system may make an elderly patient more susceptible to periodontal breakdown, age itself is not a major risk factor for periodontal diseases. Rather, individual age-associated factors such as systemic diseases, medications and changes in behavior, motor function and cognitive function should be considered for each elderly patient when making treatment decisions. PMID:26357815

  4. Accelerated Brain Aging in Schizophrenia and Beyond: A Neuroanatomical Marker of Psychiatric Disorders

    PubMed Central

    Koutsouleris, Nikolaos; Davatzikos, Christos; Borgwardt, Stefan; Gaser, Christian; Bottlender, Ronald; Frodl, Thomas; Falkai, Peter; Riecher-Rössler, Anita; Möller, Hans-Jürgen; Reiser, Maximilian; Pantelis, Christos; Meisenzahl, Eva

    2014-01-01

    Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable “accelerated aging” effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders. PMID:24126515

  5. Aging and Cerebral Palsy.

    ERIC Educational Resources Information Center

    Networker, 1993

    1993-01-01

    This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

  6. The Aging Epigenome.

    PubMed

    Booth, Lauren N; Brunet, Anne

    2016-06-01

    During aging, the mechanisms that normally maintain health and stress resistance strikingly decline, resulting in decrepitude, frailty, and ultimately death. Exactly when and how this decline occurs is unknown. Changes in transcriptional networks and chromatin state lie at the heart of age-dependent decline. These epigenomic changes are not only observed during aging but also profoundly affect cellular function and stress resistance, thereby contributing to the progression of aging. We propose that the dysregulation of transcriptional and chromatin networks is a crucial component of aging. Understanding age-dependent epigenomic changes will yield key insights into how aging begins and progresses and should lead to the development of new therapeutics that delay or even reverse aging and age-related diseases. PMID:27259204

  7. Age determination of raccoons

    USGS Publications Warehouse

    Grau, G.A.; Sanderson, G.C.; Rogers, J.P.

    1970-01-01

    Age criteria, based on 61 skulls and eye lenses from 103 known-age captives, are described for separating raccoons (Procyon lotor) into eight age-classes as follows: young-of-the-year, 1, 2, 3, 4, 5, 6-7, > 7 years. Criteria studied were eye lens nitrogen, cranial suture closure, tooth wear and incisor cementum layers. Lens nitrogen increased rapidly up to 12 months of age, but at much reduced rate thereafter. Total lens nitrogen was useful only in separating young-of-the-year from adults. The closure sequence for five cranial sutures accurately divided the total known-age sample of males into seven groups, and the adults into five groups. The tooth wear criteria divided the known-age sample into five relative age groups, but aging of individuals by this method was inaccurate. Histological sectioning of known-age teeth was the best method of observing layering in the cementum tissue. The technique of basing estimation of age on cementum ring counts, although subjective, was accurate for aging individuals through their fourth year but tended to underestimate the age of animals over 4 years old. However, suture closure or tooth wear can be used to identify males over 4 years old. In field studies, technical difficulties limit the utility of age estimation by cementum layers. Maximum root thickness of the lower canine was accurate in determining the sex of individuals from 5 months to ,at least 48 months of age.

  8. Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization

    PubMed Central

    Toba, Hiroe; de Castro Brás, Lisandra E.; Baicu, Catalin F.; Zile, Michael R.; Lindsey, Merry L.

    2015-01-01

    To investigate the role of secreted protein acidic and rich in cysteine (SPARC) in age-related cardiac inflammation, we studied six groups of mice: young (3–5 mo old), middle-aged (10–12 mo old), and old (18–29 mo old) C57BL/6 wild-type (WT) and SPARC-null (Null) mice (n = 7–10/group). Cardiac function and structure were determined by echocardiography. The left ventricle was used for cytokine gene array and macrophage quantification by immunohistochemistry. Macrophage infiltration increased with age in WT (n = 5–6/group, P < 0.05 for young vs. old), but not in Null. Proinflammatory markers (Ccl5, Cx3cl1, Ccr2, and Cxcr3) increased in middle-aged and old WT, whereas they were increased only in old Null compared with respective young (n = 5–6/group, P < 0.05 for all). These results suggest that SPARC deletion delayed age-related cardiac inflammation. To further assess how SPARC affects inflammation, we stimulated peritoneal macrophages with SPARC (n = 4). SPARC treatment increased expression of proinflammatory macrophage M1 markers and decreased anti-inflammatory M2 markers. Echocardiography (n = 7–10/group) revealed an age-related increase in wall thickness of the left ventricle in WT (0.76 ± 0.02 mm in young vs. 0.91 ± 0.03 mm in old; P < 0.05) but not in Null (0.78 ± 0.01 mm in young vs. 0.84 ± 0.02 mm in old). In conclusion, SPARC deletion delayed age-related increases in macrophage infiltration and proinflammatory cytokine expression in vivo and in vitro. SPARC acts as an important mediator of age-related cardiac inflammation by increasing the expression of macrophage M1 markers and decreasing M2 markers. PMID:25877699

  9. Trends in Neurocognitive Aging

    PubMed Central

    Grady, Cheryl

    2013-01-01

    Preface The availability of neuroimaging technology has spurred a marked increase in the human cognitive neuroscience literature, including the study of cognitive aging. Although there is a growing consensus that the aging brain retains considerable plasticity of function, currently measured primarily by means of functional magnetic resonance imaging, it is less clear how age differences in brain activity relate to cognitive performance. The field also is hampered by the complexity of the aging process itself and the large number of factors that are influenced by age. In this review, current trends and unresolved issues in the cognitive neuroscience of aging are discussed. PMID:22714020

  10. Heterogeneity in Healthy Aging

    PubMed Central

    Lowsky, David J.; Olshansky, S. Jay; Bhattacharya, Jay

    2014-01-01

    For a surprisingly large segment of the older population, chronological age is not a relevant marker for understanding, measuring, or experiencing healthy aging. Using the 2003 Medical Expenditure Panel Survey and the 2004 Health and Retirement Study to examine the proportion of Americans exhibiting five markers of health and the variation in health-related quality of life across each of eight age groups, we find that a significant proportion of older Americans is healthy within every age group beginning at age 51, including among those aged 85+. For example, 48% of those aged 51–54 and 28% of those aged 85+ have excellent or very good self-reported health status; similarly, 89% of those aged 51–54 and 56% of those aged 85+ report no health-based limitations in work or housework. Also, health-related quality of life ranges widely within every age group, yet there is only a comparatively small variation in median quality of life across age groups, suggesting that older Americans today may be experiencing substantially different age-health trajectories than their predecessors. Patterns are similar for medical expenditures. Several policy implications are explored. PMID:24249734

  11. Age to survive: DNA damage and aging.

    PubMed

    Schumacher, Björn; Garinis, George A; Hoeijmakers, Jan H J

    2008-02-01

    Aging represents the progressive functional decline and increased mortality risk common to nearly all metazoans. Recent findings experimentally link DNA damage and organismal aging: longevity-regulating genetic pathways respond to the accumulation of DNA damage and other stress conditions and conversely influence the rate of damage accumulation and its impact for cancer and aging. This novel insight has emerged from studies on human progeroid diseases and mouse models that have deficient DNA repair pathways. Here we discuss a unified concept of an evolutionarily conserved 'survival' response that shifts the organism's resources from growth to maintenance as an adaptation to stresses, such as starvation and DNA damage. This shift protects the organism from cancer and promotes healthy aging. PMID:18192065

  12. Aging and Your Eyes

    MedlinePlus

    ... Your Eyes Heath and Aging Aging and Your Eyes Steps to Protect Your Eyesight Common Eye Problems ... weight can also help protect your vision. Common Eye Problems The following common eye problems can be ...

  13. Aging According to Biography.

    ERIC Educational Resources Information Center

    Weiland, Steven

    1989-01-01

    Uses Erik Erikson's work to discuss how biographies treat aging. Explores how developmental theorists observe biographical representations of the life cycle and its applicability to aging. (Author/BHK)

  14. The aging inmate.

    PubMed

    LaMere, S; Smyer, T; Gragert, M

    1996-04-01

    Aging inmates form a distinct cultural subgroup. The antecedents for their unique patterns and needs come from the life cycle of aging within the confines of a total institution. The inmate who ages in place will lack the common social markers experienced by his age cohorts in the outside world. The aging inmate faces challenges to his self-concept related to loss of family, employment, and sexual identity. His sense of autonomy is threatened by loss of self-selective behaviors, personal possessions, and privacy. Needs of the aging prison population will challenge traditional prison resources, including correctional nursing staff and mental health and counseling services. Substantive assistance for the inmate who has aged in prison must be accompanied by an awareness of the cumulative effects of living and aging within the unique sociocultural environment of the total institution. PMID:8778405

  15. Aging and Intergenerational Relations.

    ERIC Educational Resources Information Center

    Lee, Gary R.

    1987-01-01

    Considers the rapid aging of the American population and the changing age structure of society. Discusses the needs of older adults, the role of the family in providing support to older members, and issues of intergenerational relations. (NB)

  16. Corrected Age for Preemies

    MedlinePlus

    ... Prenatal Baby Bathing & Skin Care Breastfeeding Crying & Colic Diapers & Clothing Feeding & Nutrition Preemie Sleep Teething & Tooth Care Toddler Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Baby > Preemie > Corrected Age ...

  17. Sleep and Aging: Insomnia

    MedlinePlus

    ... this page please turn Javascript on. Sleep and Aging Insomnia Insomnia is the most common sleep complaint ... us | contact us | site map National Institute on Aging | U.S. National Library of Medicine | National Institutes of ...

  18. Aging changes in immunity

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. Aging Changes and Their Effects on the Immune System ...

  19. Reverse age discrimination

    NASA Astrophysics Data System (ADS)

    Labini, Francesco Sylos; Zapperi, Stefano

    2007-09-01

    Brilliant scientists of all ages should be able to thrive at universities. Mandatory retirement is, therefore, a form of age discrimination, but its removal or postponement can come at a cost to younger faculty members, as observed in Italy.

  20. National Institute on Aging

    MedlinePlus

    ... Join Our Mailing List Email The Leader in Aging Research NIA, one of the 27 Institutes and ... broad scientific effort to understand the nature of aging and to extend the healthy, active years of ...

  1. Aging: Health Education's Responsibility.

    ERIC Educational Resources Information Center

    Wallace, Bill C.

    The elderly have recently become a target of national concern. There are currently more than 22 million people 65 years of age or older in the United States, and this number is continually increasing. Health education must respond to the need for better understanding of the aging process and the aged by including information and materials designed…

  2. Aging and Learning.

    ERIC Educational Resources Information Center

    Mayor's Office for Senior Citizens, Chicago, IL.

    The process of learning with respect to age is discussed. Learning may be defined as the acquisition of information or skills. Three non-cognitive factors varying with age are loss of speed, health, and motivation. Studies on learning in relation to age have not controlled for non-learning factors. Perceptual and psychomotor studies are not…

  3. [Aging and free radicals].

    PubMed

    Manso, C

    1992-02-01

    Several theories on aging are presented. All of them give important contributions but none explains all the aspects of the problem. Oxygen radicals produced during cellular combustion contribute to aging through multiple cumulative microlesions throughout life. The importance of glucose is emphasized; it forms early and late Maillard compounds. Other causes of aging are discussed. PMID:1595373

  4. English Education and Aging.

    ERIC Educational Resources Information Center

    Gillis, Candida

    1983-01-01

    Suggests that English teachers are in an excellent position to help students learn about the aged and aging because they know literature that treats the joys and pains of later life and they understand how language shapes and reflects cultural attitudes. Proposes objectives and presents samples of activities to be used in an aging unit. (MM)

  5. Focus on Aging.

    PubMed

    2016-06-14

    As a preview of the upcoming Cell Symposium on Aging and Metabolism in Sitges, Spain, July 10-12 (http://www.cell-symposia-aging-metabolism.com), several of our speakers and other leaders in the field share their stimulating viewpoints and theories on the complex topic of aging. PMID:27304491

  6. Resources for Aging Education.

    ERIC Educational Resources Information Center

    Cavaliere, Lorraine A.

    Following a short paper on the rationale for aging education at all levels, several resource lists cite curriculum materials and general references on aging. Aging education is defined to encompass educational programs at all levels aimed at helping students learn more about the nature and problems of growing old. Focus is on the elementary and…

  7. Physiological Aging and Exercise.

    ERIC Educational Resources Information Center

    Osness, Wayne

    This paper explores the nature of the aging process by providing an overview of the available evidence relating to the body systems that are most critical to biological function. Each system is treated separately to more clearly describe various aspects of the aging process and then integrated in a discussion of the theories of biological aging.…

  8. Exercise and Aging.

    ERIC Educational Resources Information Center

    Clarke, H. Harrison, Ed.

    1977-01-01

    In this presentation on exercise and aging, the following explanations are made: the nature of physical fitness, physical fitness values, the importance of recognizing individual differences, physiological changes occurring with age through the adult years, physical fitness studies pertaining to middle-aged persons, the trainability of older…

  9. The School Age Criminal.

    ERIC Educational Resources Information Center

    Morgenstern, Robert

    School age crime has increased a great deal in recent decades and a review of types of school age criminals may help school officials develop policies and programs to handle the problem. Both increased crime and improved news coverage have made the general public more concerned about school crime and school age criminals. A comparison of crime…

  10. The effect of whole grain consumption (WG) on diet quality and healthy eating index (HEI) scores in children aged 1 to 18 years: Results from NHANES 1999-2004

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to examine the effect of whole grain (WG) consumption on diet quality and nutrient intake in children: 2-5 y n=2,278), 6-12 y (n=3,868), and 13-18 y (n=4,931) using a secondary analysis of NHANES 1999-2004 data. Age groups were divided into four WG consumption groups:...

  11. Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes

    PubMed Central

    Li, Xiuhong; Eiden, Rina D.; Epstein, Leonard H.; Shenassa, Edmond D.; Xie, Chuanbo; Wen, Xiaozhong

    2016-01-01

    Objectives It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA) children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups. Methods Children born SGA (N = 1050) from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001–2007) was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders. Results Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06]) and math (-2.22 [-3.61, -0.84]) scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44]), but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]). Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG) had lower mean reading (-4.81 [-8.50, -1.12]) and math (-2.95 [-5.51, -0.38]) scores. These differences were not mediated by Apgar score. Conclusions Multiple-birth SGA subgroups (vs. singleton SGA) or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain) have poorer cognitive development up to 5 y. PMID:27501456

  12. UV, stress and aging.

    PubMed

    Debacq-Chainiaux, Florence; Leduc, Cedric; Verbeke, Alix; Toussaint, Olivier

    2012-07-01

    Skin is a model of choice in studies on aging. Indeed, skin aging can be modulated by internal and external factors, reflecting its complexity. Two types of skin aging have been identified: intrinsic, mainly genetically determined and extrinsic-also called "photo-aging"-resulting on the impact of environmental stress and more precisely of UV rays. Simplified in vitro models, based on cellular senescence, have been developed to study the relationship between UV and aging. These models vary on the cell type (fibroblasts or keratinocytes, normal or immortalized) and the type of UV used (UVA or UVB). PMID:23467762

  13. Carcinogenesis and aging

    SciTech Connect

    Anisimov, V.N.; Petrov, N.N.

    1987-01-01

    This 2-voluem set discusses the problem of inter-relation between carcinogenesis and aging, and the phenomenon of age-related increase in cancer incidence in animals and humans. Covered topics include current concepts in mechanisms of carcinogenesis and aging; data on chemical, radiation, ultraviolet-light, hormonal and viral carcinogenesis in aging; data on the role of age-related shifts in the activity of carcinogen-metabolizing enzymes; binding of carcinogens with macromolecules; DNA repair; tissue proliferation; and immunity and homono-metabolic patterns in realization of initiation and promotion of carcinogenesis.

  14. Can aging be 'drugged'?

    PubMed

    Riera, Celine E; Dillin, Andrew

    2015-12-01

    The engines that drive the complex process of aging are being identified by model-organism research, thereby providing potential targets and rationale for drug studies. Several studies of small molecules have already been completed in animal models with the hope of finding an elixir for aging, with a few compounds showing early promise. What lessons can we learn from drugs currently being tested, and which pitfalls can we avoid in our search for a therapeutic for aging? Finally, we must also ask whether an elixir for aging would be applicable to everyone, or whether we age differently, thus potentially shortening lifespan in some individuals. PMID:26646496

  15. Social and Emotional Aging

    PubMed Central

    Charles, Susan; Carstensen, Laura L.

    2014-01-01

    The past several decades have witnessed unidimensional decline models of aging give way to life-span developmental models that consider how specific processes and strategies facilitate adaptive aging. In part, this shift was provoked by the stark contrast between findings that clearly demonstrate decreased biological, physiological, and cognitive capacity with those suggesting that people are generally satisfied in old age and experience relatively high levels of emotional well-being. In recent years, this supposed “paradox” of aging has been reconciled through careful theoretical analysis and empirical investigation. Viewing aging as adaptation sheds light on resilience, wellbeing, and emotional distress across adulthood. PMID:19575618

  16. Aging and Vision.

    PubMed

    Alavi, Marcel V

    2016-01-01

    Aging involves defined genetic, biochemical and cellular pathways that regulate lifespan. These pathways are called longevity pathways and they have relevance for many age-related diseases. In the eye, longevity pathways are involved in the major blinding diseases, cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. Pharmaceutical targeting of longevity pathways can extend healthy lifespan in laboratory model systems. This offers the possibility of therapeutic interventions to also delay onset or slow the progression of age-related eye diseases. I suggest that retinal degeneration may be viewed as accelerated aging of photoreceptors and that interventions extending healthy lifespan may also slow the pace of photoreceptor loss. PMID:26427437

  17. Crystal structures of the Ln4-xIn 5-yS 13 ( Ln=La, Ce, Pr and Nd; x=0.08-0.12, y=0.21-0.24), La 3In 1.67S 7, Gd 3InS 6 and La 4Ag 2In 4S 13 compounds

    NASA Astrophysics Data System (ADS)

    Gulay, L. D.; Daszkiewicz, M.; Huch, M. R.

    2008-10-01

    The orthorhombic crystal structures of the series of Ln 4-xIn 5-yS 13 ( Ln=La, Ce, Pr and Nd; x=0.08-0.12, y=0.21-0.24) compounds were investigated by means of X-ray crystal diffraction. The crystals of La 3In 1.67S 7 and Gd 3InS 6 were also obtained unexpectedly from the La-In-S and Gd-In-S systems and no respective Gd 4-xIn 5-yS 13 was obtained. In the structures of the orthorhombic Ln4-xIn 5-yS 13 series and hexagonal La 3In 1.67S 7 indium atoms occupy disordered positions in the octahedral and trigonal antiprismatic arrangement of the sulphur atoms. The crystal structure of the La 4Ag 2In 4S 13 is also given and discussed as an example of quaternary sulphide related to a ternary La-In sulphide.

  18. On aging and aged care in Serbia.

    PubMed

    Sevo, G; Davidovic, M; Erceg, P; Despotovic, N; Milosevic, D P; Tasic, M

    2015-06-01

    Serbia is a demographically old nation, with 17.4 % of its residents being aged 65 years and older in 2011. The previous two decades of turbulent history have significantly affected the demographic picture of this country, and their ramifications remain visible in Serbia's economic, political, cultural, and health spheres. Major demographic forces behind population aging in Serbia can be attributed to lower fertility rates, migrations, and declining mortality (reflecting improvements in overall health leading to a longer life expectancy). In Serbia, low fertility and migrations appear to play major roles, although the relative contribution of recent migrations cannot be measured with accuracy. Patterns of demographic aging vary considerably across different geographic, socioeconomic, and cultural settings. The common denominator throughout present day Serbia is extensive political and economic transition. One would expect that, given sufficient time, this process will result in improved population health, and yet, at this stage outcomes of major health care reform in Serbia are somewhat perplexing. For the second consecutive year, Serbia's health care system has been ranked at the very bottom of the scale among 34 European countries. It is then no surprise that the elderly represent particularly vulnerable population segment. This paper discusses some of the issues relevant to these demographic patterns of aging and aged care in contemporary Serbia, focusing on the period after 2000. PMID:25943380

  19. Aging and Cancer Vaccines

    PubMed Central

    Gravekamp, Claudia; Chandra, Dinesh

    2014-01-01

    Cancer vaccination is less effective at old than at young age, due to T cell unresponsiveness. This is caused by age-related changes of the immune system. Major immune defects at older age are lack of naïve T cells, impaired activation pathways of T cells and antigen-presenting cells (APC), and age-related changes in the tumor microenvironment (TME). Also innate immune responses are affected by aging, but this seems less abundant than adaptive immune responses. In this review we compared various cancer vaccine studies at young and old age, demonstrating the importance of both innate and adaptive immune responses for cancer immunotherapy. Moreover, we found suggestive evidence that innate immune responses could help improve adaptive immune responses through cancer vaccination in old age. PMID:24579737

  20. Aging and multiple sclerosis.

    PubMed

    Sanai, Shaik Ahmed; Saini, Vasu; Benedict, Ralph Hb; Zivadinov, Robert; Teter, Barbara E; Ramanathan, Murali; Weinstock-Guttman, Bianca

    2016-05-01

    The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease-modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach. PMID:26895718

  1. Menopause accelerates biological aging.

    PubMed

    Levine, Morgan E; Lu, Ake T; Chen, Brian H; Hernandez, Dena G; Singleton, Andrew B; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E; Quach, Austin; Kusters, Cynthia D J; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E; Widschwendter, Martin; Ritz, Beate R; Absher, Devin; Assimes, Themistocles L; Horvath, Steve

    2016-08-16

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  2. The essence of aging

    PubMed Central

    Vijg, Jan; Kennedy, Brian K.

    2015-01-01

    The idea that aging is a purposeful, programmed series of events is intuitively appealing based on its many conserved aspects and the demonstrated feasibility of modifying life span by manipulating single genes or pathways. Yet, the case for a non-adaptive basis of aging is strong and now all but generally accepted in the field. Here, we briefly review why the case for programmed aging is weak, with a focus on the lack of possible evolutionary beneficial effects. PMID:26389968

  3. Muscle Changes in Aging

    PubMed Central

    Siparsky, Patrick N.; Kirkendall, Donald T.; Garrett, William E.

    2014-01-01

    Muscle physiology in the aging athlete is complex. Sarcopenia, the age-related decrease in lean muscle mass, can alter activity level and affect quality of life. This review addresses the microscopic and macroscopic changes in muscle with age, recognizes contributing factors including nutrition and changes in hormone levels, and identifies potential pharmacologic agents in clinical trial that may aid in the battle of this complex, costly, and disabling problem. Level of Evidence: Level 5. PMID:24427440

  4. Fireset materials aging study

    SciTech Connect

    Smith, H.M.; Arnold, C.; Bailey, M.E.

    1982-07-01

    A thermally-accelerated aging study of 10 selected organic materials used in a fireset has been conducted. The study included both quantitative and qualitative gas analyses as well as the measurement of physical properties before and after accelerated aging. The test plan involved single material aging, as well as pairs and larger groups to look for synergistic interactions. The material types tested were epoxies, polyurethanes, polysulfides, silicones, phenolics, polyolefins, and diallyl phthalates. Only two of the materials tested showed evidence of degradation as a result of aging.

  5. Immigration and ageing.

    PubMed

    Rowland, D T

    1986-05-01

    "This paper aims to provide an overview of immigration and ageing, and to highlight some implications of the numbers and characteristics of the immigrant elderly for the development of policies for aged care [in Australia]. Particular attention is given to the issues of demographic ageing, family support and institutionalisation." The author uses data from recent official and other published sources to examine the elderly immigrant population by birthplace and racial origin, sex, proportion institutionalized, and proportion handicapped. It is found that "insufficient recognition of the widespread lack of fluency in English among the ethnic minority aged is the greatest obstacle to achieving adequate provision for their needs." PMID:12268076

  6. [Depression and aging].

    PubMed

    Léger, J M; Clément, J P

    1992-09-01

    Old age is a qualitative state during which depression frequently occurs. This illness presents particular features which should be considered in the course of both normal ageing and senility. Viewed as an existential crisis, ageing may be considered as a depression promoting factor. Rich in depression promoting factors, this period of life is a sequence of crises which result in reorganizations heavily dependent on the adaptive capabilities of the aged person. During ageing, depression exhibits particular features that one should be able to recognize and distinguish from the consequences of deficits that are the normal adjuncts of the ageing process. The same is true of alterations occurring in the cognitive sphere and which might result from demential alteration. During ageing, depression should be identified among the other decompensation patterns occurring in the aged patient by viewing the situation in terms of overhelmed mechanisms. Depression exhibits a pattern whereby it relates closely with the risk of dementia. Therapeutic management should take into account such a perspective, that one might call transnosographic, when considering the depressiveness of aged patients as a high-risk situation requiring long-term follow-up of their biological, psychodynamic, social and cognitive functions. PMID:1308847

  7. Stem cell aging

    PubMed Central

    Muller-Sieburg, Christa; Sieburg, Hans B.

    2009-01-01

    The question whether stem cells age remains an enigma. Traditionally, aging was thought to change the properties of hematopoietic stem cells (HSC). We discuss here a new model of stem cell aging that challenges this view. It is now well-established that the HSC compartment is heterogeneous, consisting of epigenetically fixed subpopulations of HSC that differ in self-renewal and differentiation capacity. New data show that the representation of these HSC subsets changes during aging. HSC that generate lymphocyte-rich progeny are depleted, while myeloid-biased HSC are enriched in the aged HSC compartment. Myeloid-biased HSC, even when isolated from young donors, have most of the characteristics that had been attributed to aged HSC. Thus, the distinct behavior of the HSC isolated from aged hosts is due to the accumulation of myeloid-biased HSC. By extension this means that the properties of individual HSC are not substantially changed during the lifespan of the organism and that aged hosts do not contain many aged HSC. Myeloid-biased HSC give rise to mature cells slowly but contribute for a long time to peripheral hematopoiesis. We propose that such slow, “lazy” HSC are less likely to be transformed and therefore may safely sustain hematopoiesis for a long time. PMID:19066464

  8. Carcinogenesis and aging

    SciTech Connect

    Anisimov, V.N.

    1983-01-01

    A suggested mechanism of carcinogenesis is presented. This scheme takes into account the effect of carcinogens at different integration levels: subcellular, tissue, and organism. Any of these levels may be age dependent. Age-associated changes in the activity of enzymes responsible for activation and inactivation of carcinogens, and variations in concentrations of lipids and proteins contributing to the transport of carcinogenic agents into cells, may play an important role in the modifying effect of age on carcinogenesis. The effects of age-associated changes in DNA repair need clarification. However, they are thought to exert a permissive influence on the age-associated rise in tumor incidence. It seems that proliferative activity of target tissues is the important modifying factor of carcinogenesis. Age-related changes of regulation at tissue and organism levels are also powerful factors in carcinogenesis modification. Age-dependent changes in the neuroendocrine system provide conditions for metabolic immunodepression and promotion of carcinogenesis. On the other hand, carcinogens per se (especially chemical and radiological) may intensify aging processes in the organism. Normalization, by drugs, of age-associated shifts requiring synthetic and energetic changes of a transformed tumor cells, and of immunological shifts, may exert both antitumor and geroprotective effects.

  9. We Are Ageing

    PubMed Central

    Kolovou, Genovefa D.; Kolovou, Vana; Mavrogeni, Sophie

    2014-01-01

    Ageing and longevity is unquestioningly complex. Several thoughts and mechanisms of ageing such as pathways involved in oxidative stress, lipid and glucose metabolism, inflammation, DNA damage and repair, growth hormone axis and insulin-like growth factor (GH/IGF), and environmental exposure have been proposed. Also, some theories of ageing were introduced. To date, the most promising leads for longevity are caloric restriction, particularly target of rapamycin (TOR), sirtuins, hexarelin and hormetic responses. This review is an attempt to analyze the mechanisms and theories of ageing and achieving longevity. PMID:25045704

  10. Development and aging of cortical thickness correspond to genetic organization patterns

    PubMed Central

    Fjell, Anders M.; Grydeland, Håkon; Krogsrud, Stine K.; Rohani, Darius A.; Ferschmann, Lia; Storsve, Andreas B.; Tamnes, Christian K.; Sala-Llonch, Roser; Due-Tønnessen, Paulina; Bjørnerud, Atle; Sølsnes, Anne Elisabeth; Håberg, Asta K.; Skranes, Jon; Bartsch, Hauke; Chen, Chi-Hua; Thompson, Wesley K.; Panizzon, Matthew S.; Kremen, William S.; Dale, Anders M.; Walhovd, Kristine B.

    2015-01-01

    There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging. PMID:26575625

  11. Development and aging of cortical thickness correspond to genetic organization patterns.

    PubMed

    Fjell, Anders M; Grydeland, Håkon; Krogsrud, Stine K; Amlien, Inge; Rohani, Darius A; Ferschmann, Lia; Storsve, Andreas B; Tamnes, Christian K; Sala-Llonch, Roser; Due-Tønnessen, Paulina; Bjørnerud, Atle; Sølsnes, Anne Elisabeth; Håberg, Asta K; Skranes, Jon; Bartsch, Hauke; Chen, Chi-Hua; Thompson, Wesley K; Panizzon, Matthew S; Kremen, William S; Dale, Anders M; Walhovd, Kristine B

    2015-12-15

    There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging. PMID:26575625

  12. Telomeres and reproductive aging.

    PubMed

    Keefe, David L; Liu, Lin

    2009-01-01

    Infertility, miscarriage and aneuploid offspring increase with age in women, and meiotic dysfunction underlies reproductive aging. How aging disrupts meiotic function in women remains unclear, but as women increasingly delay having children, solving this problem becomes an urgent priority. Telomeres consist of a (TTAGGG)(n) repeated sequence and associated proteins at chromosome ends, mediate aging in mitotic cells and may also mediate aging during meiosis. Telomeres shorten both during DNA replication and from the response to oxidative DNA damage. Oocytes do not divide in adult mammals, but their precursors do replicate during fetal oogenesis; eggs ovulated from older females have traversed more mitotic cell cycles before entering meiosis during fetal oogenesis than eggs ovulated from younger females. Telomeres also would be expected to shorten from inefficient DNA repair of oxidative damage, because the interval between fetal oogenesis and ovulation is exceptionally prolonged in women. We have tested the hypothesis that telomere shortening disrupts meiosis by shortening telomeres experimentally in mice, which normally do not exhibit age-related meiotic dysfunction. Interestingly, mouse telomeres are much longer than human telomeres, but genetic or pharmacological shortening of mouse telomeres recapitulates in mice the human reproductive aging phenotype as the mouse telomeres reach the length of telomeres from older women. These observations led us to propose a telomere theory of reproductive aging. Moreover, chronological oxidative stress increases with reproductive aging, leading to DNA damage preferentially at (TTAGGG)(n) repeats. Finally, if telomeres shorten with aging, how do they reset across generations? Telomerase could not play a significant role in telomere elongation during early development, because this enzyme is not active until the blastocyst stage, well after the stage when telomere elongation takes place. Rather, telomeres lengthen during the

  13. Cable aging phenomena under accelerated aging conditions

    SciTech Connect

    Behera, A.K.; Beck, C.E.; Alsammarae, A.

    1996-06-01

    A test program was conducted to determine the impact of accelerated (temperature and radiation) aging on the insulation of power cables. The intent was to develop a more realistic model for cable degradation mechanisms, and a more realistic technique for determining a cable`s qualified life. Samples of new cables and samples of cables obtained from an operating plant were subjected to a series of tests. The test showed that the order of imposing the harsh conditions, the presence of oxygen, and the use of a compressive measurement technique each had a significant impact on the results. This paper discusses the test methodology and test samples, the order of imposing artificial aging, and the results. Also presented are issues planned to be addressed in future testing.

  14. Materials Data on Nd5Mo3O16 (SG:222) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-07-09

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  15. Materials Data on Y5(MoO6)2 (SG:12) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  16. Crystallographic peculiarities of the eutectoid and martensite structures in the U-1.5 % Mo alloy

    NASA Astrophysics Data System (ADS)

    Kabanova, I. G.; Klyukina, M. F.; Sagaradze, V. V.; Pecherkina, N. L.; Zuev, Yu. N.

    2016-06-01

    Using electron microscopy, samples of U-1.5 wt % Mo alloy with a partial structure of eutectoid, which consists of alternating plates of α phase depleted of molybdenum (α-U) and ordered γ' phase (U2Mo), have been studied. The structures of a eutectoid and martensite have been obtained by the quenching of samples characterized by delayed cooling from 1000°C. It has been shown that, in the eutectoid, the constant orientation relationships (ORs) are observed between the α-U and U2Mo phases, namely, {[ {100} ]_α }{| {[ {331} ]} ._{γ '}},{( {010} )_α }{| {( {11bar 6} )} ._{γ '}},{( {010} )_α }{| {( {bar 110} )} ._{γ '}} These relationships are similar to the ORs observed in the martensite between an orthorhombic α' martensite and initial bcc γ phase that have been found in low alloys of U-Nb, U-Zr, U-Mo and experimentally confirmed in this work. It has been established that, in the γ' phase, principal axes a, b, c remain parallel to the principal axes of the matrix γ phase. However, its axis of tetragonality c has the only nonequivalent crystallographic direction at which the plates in the eutectoid colonies that are parallel to the planes of atomic ordering of the γ' phase have interphase boundaries of (001)_{γ '} ||(130)_α.

  17. Aging and Work Organizations.

    ERIC Educational Resources Information Center

    Schrank, Harris T.; Waring, Joan M.

    Business firms are an integral part of the age stratification structure of society. Although the age structures of people and roles within the organization are dynamic, these structures yield a fairly stable strata in which norms exist to suggest the various roles expected of certain persons. Those in roles with greater financial rewards, power,…

  18. New Dimensions on Aging.

    ERIC Educational Resources Information Center

    Randall, Ollie

    This brief presentation discusses various problems older adults face. First, older adults are described, and old age is defined. Old age starts after 50, and older adults should not be considered as a homogeneous group; thay fall into many different categories which enrich rather than impoverish them as a group. The long experience they have had…

  19. Towards Consensus Gene Ages

    PubMed Central

    Liebeskind, Benjamin J.; McWhite, Claire D.; Marcotte, Edward M.

    2016-01-01

    Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene’s age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914

  20. The Age of Majority.

    ERIC Educational Resources Information Center

    Council of State Governments, Lexington, KY.

    During the past 2 years state laws lowering the age of majority to 18 and other statutes that confer some majority rights on minors have considerably altered the status of young people in our society. In 7 states, the age of majority has been lowered in an effort to relieve young people of the minority disabilities originally intended to protect…

  1. Blueberries and neuronal aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As the population of people in the United States over the age of 65 years continues to increase, so too will the incidence of age-related pathologies, including decreases in cognitive and motor function. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care ...

  2. Age and Scientific Performance.

    ERIC Educational Resources Information Center

    Cole, Stephen

    1979-01-01

    The long-standing belief that age is negatively associated with scientific productivity and creativity is shown to be based upon incorrect analysis of data. Studies reported in this article suggest that the relationship between age and scientific performance is influenced by the operation of the reward system. (Author)

  3. Towards Consensus Gene Ages.

    PubMed

    Liebeskind, Benjamin J; McWhite, Claire D; Marcotte, Edward M

    2016-01-01

    Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene's age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914

  4. Adventures of Aging.

    ERIC Educational Resources Information Center

    Wright, Gloria O.

    There is nothing in American society to prepare women for aging. It has been proposed that the status that the aged hold in any culture diminishes when modernization, an increased number and proportion of elderly, or rapid social change is present. All three of these conditions exist in American society. Women face many dangers, especially as they…

  5. Entrance Age Policies.

    ERIC Educational Resources Information Center

    Stemnock, Suzanne K.

    1968-01-01

    This survey sought information regarding the policies of school districts across the nation on entrance requirements to kindergarten and the first grade. The school systems were classified under four strata according to total enrollment size. The most frequently reported minimum entrance age for kindergarten was 5 years of age by December 1. For…

  6. Adulthood and Aging.

    ERIC Educational Resources Information Center

    Thomas, Jeanne L.

    This textbook is designed to introduce undergraduates to the scientific study of aging in adults. Among the topics covered in the book's 15 chapters are: approaches to the study of adult development and aging (research methodology and related issues, a life-span perspective, ethical issues); theories in the study of adult development (models of…

  7. Learning and Active Aging

    ERIC Educational Resources Information Center

    Boulton-Lewis, Gillian M.; Buys, Laurie; Lovie-Kitchin, Jan

    2006-01-01

    Learning is an important aspect of aging productively. This paper describes results from 2645 respondents (aged from 50 to 74+ years) to a 165-variable postal survey in Australia. The focus is on learning and its relation to work; social, spiritual, and emotional status; health; vision; home; life events; and demographic details. Clustering…

  8. Myocontrol in Aging

    PubMed Central

    Fimbel, Eric J.; Arguin, Martin

    2007-01-01

    Myoelectric (EMG) signals are used in assistive technology for prostheses, computer and domestic control. An experimental study previously conducted with young participants was replicated with elderly persons in order to assess the effect of age on the ability to control myoelectric amplitude (or myocontrol). Participants performed pointing tasks as the myoelectric amplitude was captured by a surface electrode in two modalities (sustained: stabilize the amplitude after reaching the desired level; impulsion: return immediately to resting amplitude). There was a significant decrease of performance with Age. However, the patterns of performance of young and aged were noticeably similar. The Impulsion modality was difficult (high rates of failure) and the speed-accuracy trade-offs predicted by Fitts' law were absent (bow-shaped patterns as function of target amplitude instead of logarithmic increase). Conversely, the reach phase of the Sustained modality followed the predictions of Fitts' law. However, the slope of the regression line with Fitts' index of difficulty was quite steeper in aged than in young participants. These findings suggest that 1) all participants, young and aged, adapt their reaching strategies to the anticipated state (sustained amplitude or not) and/or to the difficulty of the task, 2) myocontrol in aged persons is more fragile, i.e., performance is markedly degraded as the difficulty of the task increases. However, when individual performance was examined, some aged individuals were found to perform as well as the young participants, congruently with the literature on good aging. PMID:18030349

  9. "Brainberries" and Aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The onset of age-related neurodegenerative diseases superimposed on a declining nervous system could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. This means that unless some way is found to reduce these age-related declines in neuronal function, health ca...

  10. Curriculum Activities on Aging.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; Benge, Nancy

    This paper contains learning activities on aging for use with elementary, high school, and university students in health, family relationships, social studies, and art courses. The activities are intended to help youth develop a more realistic understanding of the aging process and to become aware of both the problems and benefits associated with…

  11. A Respectable Old Age.

    ERIC Educational Resources Information Center

    Swensen, Clifford H.

    1983-01-01

    Contrasts the relatively abundant information on the young with the paucity of research knowledge on the aged, and asserts that psychologists have too few solutions to coping with the problems of aging. Suggests the integration of older adults into all aspects of society through structural change. (Author/AOS)

  12. Selected Issues on Aging.

    ERIC Educational Resources Information Center

    Gordon, Ruby D.

    Aging is a continuum which begins at birth and ends at death. A multidisciplinary approach is necessary to the study of aging as a part of developmental psychology. The individual is a biological organism as well as a member of society. Biological adjustments to life are affected by physical changes which influence motives and emotions. Some of…

  13. Perspective on Aging

    ERIC Educational Resources Information Center

    Youry, Mary, Ed.

    1975-01-01

    This issue follows up the 25th Annual Conference of the National Council on the Aging (NCOA). Title XX, the "grants to States for Services", and public policy statements issued by NCOA's board of directors are presented. Convention workshops on civil rights of older people, trends in center designs, and area agencies on aging are described.…

  14. Epigenetics of Aging

    PubMed Central

    Sierra, Marta I.; Fernández, Agustín F.; Fraga, Mario F.

    2015-01-01

    The best-known phenomenon exemplifying epigenetic drift (the alteration of epigenetic patterns during aging) is the gradual decrease of global DNA methylation. Aging cells, different tissue types, as well as a variety of human diseases possess their own distinct DNA methylation profiles, although the functional impact of these is not always clear. DNA methylation appears to be a dynamic tool of transcriptional regulation, with an extra layer of complexity due to the recent discovery of the conversion of 5-methylcytosine into 5-hydroxymethylcytosine. This age-related DNA demethylation is associated with changes in histone modification patterns and, furthermore, we now know that ncRNAs have evolved in eukaryotes as epigenetic regulators of gene expression. In this review, we will discuss current knowledge on how all these epigenetic phenomena are implicated in human aging, and their links with external, internal and stochastic factors which can affect human age-related diseases onset. PMID:27019618

  15. Implications of Vascular Aging

    PubMed Central

    Barodka, Viachaslau M.; Joshi, Brijen L.; Berkowitz, Dan E.; Hogue, Charles W.; Nyhan, Daniel

    2011-01-01

    Chronological age is a well established risk factor for the development of cardiovascular diseases. The changes that accumulate in the vasculature with age, though, are highly variable. It is now increasingly recognized that indices of vascular health are more reliable than age per se in predicting adverse cardiovascular outcomes. The variation in the accrual of these age-related vascular changes is a function of multiple genetic and environmental factors. In this review, we highlight some of the pathophysiological mechanisms that characterize the vascular aging phenotype. Furthermore, we provide an overview of the key outcome studies that address the value of these vascular health indices in general and discuss potential effects on perioperative cardiovascular outcomes. PMID:21474663

  16. Cooee bitumen: chemical aging.

    PubMed

    Lemarchand, Claire A; Schrøder, Thomas B; Dyre, Jeppe C; Hansen, Jesper S

    2013-09-28

    We study chemical aging in "Cooee bitumen" using molecular dynamic simulations. This model bitumen is composed of four realistic molecule types: saturated hydrocarbon, resinous oil, resin, and asphaltene. The aging reaction is modelled by the chemical reaction: "2 resins → 1 asphaltene." Molecular dynamic simulations of four bitumen compositions, obtained by a repeated application of the aging reaction, are performed. The stress autocorrelation function, the fluid structure, the rotational dynamics of the plane aromatic molecules, and the diffusivity of each molecule are determined for the four different compositions. The aging reaction causes a significant dynamics slowdown, which is correlated to the aggregation of asphaltene molecules in larger and dynamically slower nanoaggregates. Finally, a detailed description of the role of each molecule types in the aggregation and aging processes is given. PMID:24089785

  17. Aging and Language Production

    PubMed Central

    Burke, Deborah M.; Shafto, Meredith A.

    2008-01-01

    Experimental research and older adults’ reports of their own experience suggest that the ability to produce the spoken forms of familiar words declines with aging. Older adults experience more word-finding failures, such as tip-of-the-tongue states, than young adults do, and this and other speech production failures appear to stem from difficulties in retrieving the sounds of words. Recent evidence has identified a parallel age-related decline in retrieving the spelling of familiar words. Models of cognitive aging must explain why these aspects of language production decline with aging whereas semantic processes are well maintained. We describe a model wherein aging weakens connections among linguistic representations, thereby reducing the transmission of excitation from one representation to another. The structure of the representational systems for word phonology and orthography makes them vulnerable to transmission deficits, impairing retrieval. PMID:18414600

  18. Parylene C Aging Studies.

    SciTech Connect

    Achyuthan, Komandoor; Sawyer, Patricia Sue.; Mata, Guillermo Adrian; White II, Gregory Von; Bernstein, Robert

    2014-09-01

    Parylene C is used in a device because of its conformable deposition and other advantages. Techniques to study Parylene C aging were developed, and "lessons learned" that could be utilized for future studies are the result of this initial study. Differential Scanning Calorimetry yielded temperature ranges for Parylene C aging as well as post-deposition treatment. Post-deposition techniques are suggested to improve Parylene C performance. Sample preparation was critical to aging regimen. Short-term (%7E40 days) aging experiments with free standing and ceramic-supported Parylene C films highlighted "lessons learned" which stressed further investigations in order to refine sample preparation (film thickness, single sided uniform coating, machine versus laser cutting, annealing time, temperature) and testing issues ("necking") for robust accelerated aging of Parylene C.

  19. Genetics and skin aging

    PubMed Central

    Makrantonaki, Evgenia; Bekou, Vassiliki; Zouboulis, Christos C.

    2012-01-01

    Skin aging is a complex process and underlies multiple influences with the probable involvement of heritable and various environmental factors. Several theories have been conducted regarding the pathomechanisms of aged skin, however fundamental mechanisms still remain poorly understood. This article addresses the influence of genetics on skin aging and in particular deals with the differences observed in ethnic populations and between both genders. Recent studies indicate that male and female aged skin differs as far as the type, the consistency and the sensitivity to external factors is concerned. The same has been also documented between elderly people of different origin. Consequently, the aging process taking place in both genders and in diverse ethnic groups should be examined separately and products specialized to each population should be developed in order to satisfy the special needs. PMID:23467395

  20. Ageing and the brain.

    PubMed

    Peters, R

    2006-02-01

    Ageing causes changes to the brain size, vasculature, and cognition. The brain shrinks with increasing age and there are changes at all levels from molecules to morphology. Incidence of stroke, white matter lesions, and dementia also rise with age, as does level of memory impairment and there are changes in levels of neurotransmitters and hormones. Protective factors that reduce cardiovascular risk, namely regular exercise, a healthy diet, and low to moderate alcohol intake, seem to aid the ageing brain as does increased cognitive effort in the form of education or occupational attainment. A healthy life both physically and mentally may be the best defence against the changes of an ageing brain. Additional measures to prevent cardiovascular disease may also be important. PMID:16461469

  1. Overview of facial aging.

    PubMed

    Beer, Kenneth; Beer, Jacob

    2009-12-01

    Facial aging is a multidimensional, multifactorial process. The aging face has traditionally been treated by each specialty in a different manner. However, by understanding the process from the perspective of different specialties, each physician may better treat the spectrum of facial aging. Whether or not the facial plastic surgeon injects products to restore volume, uses lasers to resurface the epidermis and dermis, incorporates cosmeceuticals to enhance and maintain improvements in the skin integrity and appearance, or relaxes muscles with botulinum toxins, he or she can best advise patients and address facial aging by having a functional understanding of these various modalities. With this knowledge, the facial plastic surgeon can parse the component of facial aging that enables him or her to correct each with the appropriate treatment. PMID:20024868

  2. Platelet function and ageing.

    PubMed

    Jones, Chris I

    2016-08-01

    There are clear age-related changes in platelet count and function, driven by changes in hematopoietic tissue, the composition of the blood and vascular health. Platelet count remains relatively stable during middle age (25-60 years old) but falls in older people. The effect of age on platelet function is slightly less clear. The longstanding view is that platelet reactivity increases with age in an almost linear fashion. There are, however, serious limitations to the data supporting this dogma. We can conclude that platelet function increases during middle age, but little evidence exists on the changes in platelet responsiveness in old age (>75 years old). This change in platelet function is driven by differential mRNA and microRNA expression, an increase in oxidative stress and changes in platelet receptors. These age-related changes in platelets are particularly pertinent given that thrombotic disease and use of anti-platelet drugs is much more prevalent in the elderly population, yet the majority of platelet research is carried out in young to middle-aged (20-50 years old) human volunteers and young mice (2-6 months old). We know relatively little about exactly how platelets from people over 75 years old differ from those of middle-aged subjects, and we know even less about the mechanisms that drive these changes. Addressing these gaps in our knowledge will provide substantial understanding in how cell signalling changes during ageing and will enable the development of more precise anti-platelet therapies. PMID:27068925

  3. Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of {sup 239}Pu or {sup 226}Ra

    SciTech Connect

    Lloyd, R.D.; Taylor, G.N.; Jee, W.S.S.; Miller, S.C.

    1999-01-01

    A comparison was made of the response to induction of skeletal malignancy from exposure of beagles to monomeric {sup 239}Pu or to {sup 226}Ra as juveniles (3 mo of age), young adults (1.5 y of age), or mature adults (5 y of age). This indicated that of these age groups, animals injected as young adults are most sensitive per Gy of average skeletal dose evaluated at 1 y before death. Dogs exposed either as juveniles or as mature adults appeared to be less sensitive. Relative radiosensitivities (RRS) of juvenile and mature beagles ranged between about 0.3 and 0.7 that of dogs injected as young adults. Mean values of RRS for both radionuclides were about 0.5, but RRS values derived from dogs given monomeric {sup 239}Pu appeared to be most reliable and were 0.27 {+-} 0.09 for dogs injected as juveniles and 0.41 {+-} 0.13 for animals exposed as mature adults.

  4. Epigenetics and aging.

    PubMed

    Pal, Sangita; Tyler, Jessica K

    2016-07-01

    Over the past decade, a growing number of studies have revealed that progressive changes to epigenetic information accompany aging in both dividing and nondividing cells. Functional studies in model organisms and humans indicate that epigenetic changes have a huge influence on the aging process. These epigenetic changes occur at various levels, including reduced bulk levels of the core histones, altered patterns of histone posttranslational modifications and DNA methylation, replacement of canonical histones with histone variants, and altered noncoding RNA expression, during both organismal aging and replicative senescence. The end result of epigenetic changes during aging is altered local accessibility to the genetic material, leading to aberrant gene expression, reactivation of transposable elements, and genomic instability. Strikingly, certain types of epigenetic information can function in a transgenerational manner to influence the life span of the offspring. Several important conclusions emerge from these studies: rather than being genetically predetermined, our life span is largely epigenetically determined; diet and other environmental influences can influence our life span by changing the epigenetic information; and inhibitors of epigenetic enzymes can influence life span of model organisms. These new findings provide better understanding of the mechanisms involved in aging. Given the reversible nature of epigenetic information, these studies highlight exciting avenues for therapeutic intervention in aging and age-associated diseases, including cancer. PMID:27482540

  5. [Normal aging and cognition].

    PubMed

    Ska, Bernadette; Joanette, Yves

    2006-03-01

    It is now well documented that normal aging modifies the cognitive functioning and most observations suggest that cognition evolves in the direction of deterioration. The more frequently impaired functions are memory, attention and visual-spatial abilities. On the other hand, some abilities seem to increase, such as vocabulary. Considering the aging effect on cognition, questions remain regarding directionality, universality and reversibility. A great variability in aged related impacts is observed among subjects and among cognitive domains. Some individuals evolved more rapidly than others. Some cognitive functions are more affected by aging than others. General and specific factors are hypothesized to explain the aged related cognitive decline. Among them, educational level, health, cognitive style, life style, personality, are likely to modulate the aged related cognitive evolution by influencing attentional resources and cerebral plasticity. Cognitive resources are essential to develop adaptative strategies. During the life span, resources are activated and increased by learning and training. Considering the role of cognitive resources, successful aging is dependent on several conditions : absence of disease leading to a loss of autonomy, maintenance of cognitive and physical activities, and active and social engaged lifestyle. PMID:16527210

  6. Epigenetics and aging

    PubMed Central

    Pal, Sangita; Tyler, Jessica K.

    2016-01-01

    Over the past decade, a growing number of studies have revealed that progressive changes to epigenetic information accompany aging in both dividing and nondividing cells. Functional studies in model organisms and humans indicate that epigenetic changes have a huge influence on the aging process. These epigenetic changes occur at various levels, including reduced bulk levels of the core histones, altered patterns of histone posttranslational modifications and DNA methylation, replacement of canonical histones with histone variants, and altered noncoding RNA expression, during both organismal aging and replicative senescence. The end result of epigenetic changes during aging is altered local accessibility to the genetic material, leading to aberrant gene expression, reactivation of transposable elements, and genomic instability. Strikingly, certain types of epigenetic information can function in a transgenerational manner to influence the life span of the offspring. Several important conclusions emerge from these studies: rather than being genetically predetermined, our life span is largely epigenetically determined; diet and other environmental influences can influence our life span by changing the epigenetic information; and inhibitors of epigenetic enzymes can influence life span of model organisms. These new findings provide better understanding of the mechanisms involved in aging. Given the reversible nature of epigenetic information, these studies highlight exciting avenues for therapeutic intervention in aging and age-associated diseases, including cancer. PMID:27482540

  7. Three ages of Venus

    NASA Technical Reports Server (NTRS)

    Wood, Charles A.; Coombs, Cassandra R.

    1989-01-01

    A central question for any planet is the age of its surface. Based on comparative planetological arguments, Venus should be as young and active as the Earth (Wood and Francis). The detection of probable impact craters in the Venera radar images provides a tool for estimating the age of the surface of Venus. Assuming somewhat different crater production rates, Bazilevskiy et al. derived an age of 1 + or - 0.5 billion years, and Schaber et al. and Wood and Francis estimated an age of 200 to 400 million years. The known impact craters are not randomly distributed, however, thus some area must be older and others younger than this average age. Ages were derived for major geologic units on Venus using the Soviet catalog of impact craters (Bazilevskiy et al.), and the most accessible geologic unit map (Bazilevskiy). The crater counts are presented for (diameters greater than 20 km), areas, and crater densities for the 7 terrain units and coronae. The procedure for examining the distribution of craters is superior to the purely statistical approaches of Bazilevskiy et al. and Plaut and Arvidson because the bins are larger (average size 16 x 10(6) sq km) and geologically significant. Crater densities define three distinct groups: relatively heavily cratered (Lakshmi, mountain belts), moderately cratered (smooth and rolling plains, ridge belts, and tesserae), and essentially uncratered (coronae and domed uplands). Following Schaber et al., Grieve's terrestrial cratering rate of 5.4 + or - 2.7 craters greater than 20 km/10(9) yrs/10(6) sq km was used to calculate ages for the geologic units on Venus. To improve statistics, the data was aggregated into the three crater density groups, deriving the ages. For convenience, the three similar age groups are given informal time stratigraphic unit names, from youngest to oldest: Ulfrunian, Sednaian, Lakshmian.

  8. [Work capacity and aging].

    PubMed

    Costa, G

    2000-01-01

    Maintaining a good work ability depends on satisfactory health and employment status, which is supported by suitable working conditions and correct life styles. From the biological perspective, ageing means a foreseeable progressive and overall deterioration of the various physiological systems, but not of such a kind and severity to consider most people over 50 as too old or unfit for work, as has been shown by several studies that assessed work ability not only in terms of biological age, but of functional age and actual work output. From the physio-pathological perspective, we can observe either illnesses associated with the passage of time or age-related changes that might precipitate diseases, as well as environmental changes that modulate ageing and developmental changes that accelerate or retard ageing. From the practical point of view, it should taken into account that job demands often do not follow the natural biological and functional changes of the individual, consequently the relative work load can be higher in older workers. On the other hand, ageing also means a professional growth in terms of strategic ability, shrewdness, wisdom and experience. The high interindividual variability of physical, mental and social conditions that is observed with the increase in age makes it necessary to adopt flexible and personally tailored measures, as shown by recent surveys in some European countries aimed at reducing age discrimination and work disability, and at promoting work ability by means of actions directed towards both improvement of work organisation and support of psycho-physical conditions of older workers. PMID:11098594

  9. Aging and variety seeking.

    PubMed

    Novak, Deanna L; Mather, Mara

    2007-12-01

    The authors examined the influence of age on variety seeking in 3 experiments. When given choices among jellybeans or music, age differences in variety seeking emerged. Younger adults selected similar levels of variety when choosing what to consume immediately and what to consume later. In contrast, older adults consistently chose less variety when making choices to be consumed at a later time than when making choices to be consumed immediately. This pattern may be related to an increased focus on regulating future emotional experience that is associated with age. PMID:18179293

  10. The transparency of aging.

    PubMed

    Sorrell, Jeanne M

    2007-03-01

    This article is not meant to provide answers but to provoke thinking related to the questions we should be asking about the ethical personhood of aging adults. Are we covering over the rich opportunities to learn from their stories with an invisible cloak of transparency? Health care professionals have a moral obligation to rethink the assumptions that underlie their definitions of quality of life in aging. We cannot know what should be done unless we learn to listen to the life stories of aging people. This may even help us to see what is most real. PMID:17396715

  11. Envy, Politics, and Age

    PubMed Central

    Harris, Christine R.; Henniger, Nicole E.

    2013-01-01

    In the last 5 years, the phrase “politics of envy” has appeared more than 621 times in English-language newspapers, generally in opinion essays contending that political liberalism reflects and exploits feelings of envy. Oddly, this assertion has not been tested empirically. We did so with a large adult sample (n = 357). Participants completed a Dispositional Envy Scale and questions about political ideology, socioeconomic status, and age. Envy and age were moderately correlated; younger people reported greater envy. Political ideology and envy were weakly correlated; however, this relationship was not significant when controlling for age. PMID:23471177

  12. Ageing and its implications

    PubMed Central

    Jayanthi, P; Joshua, Elizabeth; Ranganathan, K

    2010-01-01

    Ageing processes are defined as those that increase the susceptibility of individuals, as they grow older, to the factors that eventually lead to death. It is a complex multi-factorial process, where several factors may interact simultaneously and may operate at many levels of functional organization. The heterogeneity of ageing phenotype among individuals of the same species and differences in longevity among species are due to the contribution of both genetic and environmental factors in shaping the life span. The various theories of ageing and their proposed roles are discussed in this review. PMID:21731262

  13. [Epidermal aging and anti-aging strategies].

    PubMed

    Wohlrab, J; Hilpert, K; Wolff, L

    2016-02-01

    Epithelial senescence is a complex process depending on intrinsic as well as extrinsic factors (e.g., UV or IR light, tobacco smoke) and must be seen in the context of the aging process especially of the corium and the subcutis. Morphological alterations become apparent in the form of epithelial atrophy, structural changes within the basal membrane, and a decrease in cell count of melanocytes and Langerhans cells. Signs of cellular senescence are reduced proliferation of keratinocytes, cumulation of dysplastic keratinocytes, various mutations (e.g., c-Fos/c-Jun, STAT3, FoxO1), as well as multiple lipid or amino acid metabolic aberrations (e.g., production of advanced glycation endproducts). This causes functional changes within the physical (lipid deficiency, water distribution dysfunction, lack of hygroscopic substances), chemical (pH conditions, oxygen radicals), and immunological barrier. Prophylactically, barrier-protective care products, antioxidant substances (e.g., vitamin C, B3, E, polyphenols, flavonoids), sunscreen products/measurements, and retinoids are used. For correcting alterations in aged epidermis, chemical peelings (fruit acids, β-hydroxy acid, trichloroacetic acid, phenolic compounds), non-ablative (IPL, PDL, Nd:YAG) as well as ablative (CO2, Erbium-YAG) light-assisted methods are used. PMID:26636143

  14. Cellular Homeostasis and Aging.

    PubMed

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  15. HEU age determination

    SciTech Connect

    Moorthy, A.R.; Kato, W.Y.

    1995-08-01

    A technique has been developed to determine the Highly Enriched Uranium (HEU) Age which is defined as the time since the HEU was produced in an enrichment process. The HEU age is determined from the ratios of relevant uranium parents and their daughters viz {sup 230}Th/{sup 234}U and {sup 231}Pa/{sup 235}U. Uranium isotopes are quantitatively measured by their characteristic gammas and their daughters by alpha spectroscopy. In some of the samples where HEU is enriched more than 99%, the only mode of HEU age determination is by the measurement of {sup 231}Pa since there is negligible quantity of {sup 230}Th due to very low atom concentrations of {sup 234}U in the sample. In this paper we have presented data and methodology of finding the age of two HEU samples.

  16. Age and Language Learning

    ERIC Educational Resources Information Center

    Collard, Lucien

    1977-01-01

    An investigation of the differences between first and second language acquisition and the relationship between age and second language learning. The stages in native language acquisition and the advantages of an early start in second language learning are discussed. (AMH)

  17. Healthy Aging -- Sexual Health

    MedlinePlus

    ... than ever after menopause. But for other women, physical changes, illness, disabilities, and some medicines make sex painful, ... in Later Life - This brochure describes the normal physical changes in men and women that come with age. ...

  18. Air Age Education Workshop.

    ERIC Educational Resources Information Center

    Journal of Aerospace Education, 1978

    1978-01-01

    Describes a three-day program aimed at public school educators and community leaders. The goal was to encourage these people to include air age education in their programs. Activities included hands-on projects. (MA)

  19. Aging Water Infrastructure

    EPA Science Inventory

    The Aging Water Infrastructure (AWI) research program is part of EPA’s larger effort called the Sustainable Water Infrastructure (SI) initiative. The SI initiative brings together drinking water and wastewater utility managers; trade associations; local watershed protection organ...

  20. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.