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1

Role of protein kinase C? in UV-B-induced apoptosis of macrophages in vitro  

Microsoft Academic Search

We have previously reported that murine peritoneal macrophages exposed to ultraviolet B (UV-B; 100 mJ\\/cm2) undergo apoptosis, as indicated by alterations in cell morphology, caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage, DNA fragmentation, sustained activation of p38\\/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) and inactivation of p42\\/44 MAPKs. It is now reported that macrophages undergoing UV-B-induced apoptosis show enhanced

Ajit Sodhi; Gautam Sethi

2005-01-01

2

Epothilone B induces extrinsic pathway of apoptosis in human SKOV-3 ovarian cancer cells.  

PubMed

The molecular mechanisms underlying epothilone B (EpoB) induced apoptosis were investigated in SKOV-3 human ovarian cancer cells. The aim of this research was to compare EpoB's, which belongs to the new class of anticancer drugs, with paclitaxel's (PTX) ability to induce apoptosis. The mode of cell death was assessed colorimetrically, fluorimetrically and by immunoblot analyses through measuring DNA fragmentation, the level of intracellular calcium, the level of cytochrome c, TRAIL, the cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-9, -8 and -3. EpoB leads to an increase of the cytosolic level of cytochrome c after 4 h of cell treatment. After 24 and 48 h of cell treatment the level of intracellular calcium also increased by about 21% and 24% respectively. Moreover, EpoB, similarly to PTX, promoted the expression of TRAIL in lymphocytes, although high TRAIL expression on tumor cells was detected only after adding EpoB to SKOV-3 cells. EpoB mediates caspases-8 and -3 activation, which is independent of the reduction in the amount of caspase-9. Epitope-specific monoclonal and polyclonal antibodies revealed characteristic apoptotic changes that included cleavage of the 116 kDa PARP polypeptide to 25 kDa fragments. The results of our study show that EpoB induces mainly the extrinsic pathway. PMID:24583341

Rogalska, Aneta; Gajek, Arkadiusz; Marczak, Agnieszka

2014-06-01

3

The Marine Fungal Metabolite, Dicitrinone B, Induces A375 Cell Apoptosis through the ROS-Related Caspase Pathway  

PubMed Central

Dicitrinone B, a rare carbon-bridged citrinin dimer, was isolated from the marine-derived fungus, Penicillium citrinum. It was reported to have antitumor effects on tumor cells previously; however, the details of the mechanism remain unclear. In this study, we found that dicitrinone B inhibited the proliferation of multiple tumor types. Among them, the human malignant melanoma cell, A375, was confirmed to be the most sensitive. Morphologic evaluation, cell cycle arrest and apoptosis rate analysis results showed that dicitrinone B significantly induced A375 cell apoptosis. Subsequent observation of reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) reduction revealed that the apoptosis induced by dicitrinone B may be triggered by over-producing ROS. Further studies indicated that the apoptosis was associated with both intrinsic and extrinsic apoptosis pathways under the regulation of Bcl-2 family proteins. Caspase-9, caspase-8 and caspase-3 were activated during the process, leading to PARP cleavage. The pan-caspase inhibitor, Z-VAD-FMK, could reverse dicitrinone B-induced apoptosis, suggesting that it is a caspase-dependent pathway. Our data for the first time showed that dicitrinone B inhibits the proliferation of tumor cells by inducing cell apoptosis. Moreover, compared with the first-line chemotherapy drug, 5-fluorouracil (5-Fu), dicitrinone B showed much more potent anticancer efficacy, suggesting that it might serve as a potential antitumor agent. PMID:24699111

Chen, Li; Gong, Mei-Wei; Peng, Zhen-Fei; Zhou, Tong; Ying, Min-Gang; Zheng, Qiu-Hong; Liu, Qin-Ying; Zhang, Qi-Qing

2014-01-01

4

The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1  

PubMed Central

Recently, Salmonella spp. were shown to induce apoptosis in infected macrophages. The mechanism responsible for this process is unknown. In this report, we establish that the Inv-Spa type III secretion apparatus target invasin SipB is necessary and sufficient for the induction of apoptosis. Purified SipB microinjected into macrophages led to cell death. Binding studies show that SipB associates with the proapoptotic protease caspase-1. This interaction results in the activation of caspase-1, as seen in its proteolytic maturation and the processing of its substrate interleukin-1?. Caspase-1 activity is essential for the cytotoxicity. Functional inhibition of caspase-1 activity by acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone blocks macrophage cytotoxicity, and macrophages lacking caspase-1 are not susceptible to Salmonella-induced apoptosis. Taken together, the data demonstrate that SipB functions as an analog of the Shigella invasin IpaB. PMID:10051653

Hersh, David; Monack, Denise M.; Smith, Mark R.; Ghori, Nafisa; Falkow, Stanley; Zychlinsky, Arturo

1999-01-01

5

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways  

SciTech Connect

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ? We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ? EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ? The effects are involved in caspase-dependent apoptosis and p53 pathway. ? In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ? EriB can be a good candidate for chemotherapy in pancreatic cancer.

Li, Lin [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China) [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Yue, Grace G.L. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Lau, Clara B.S. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Sun, Handong [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China)] [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China); Fung, Kwok Pui [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China) [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Leung, Ping Chung [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Han, Quanbin, E-mail: simonhan@hkbu.edu.hk [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong (China); Leung, Po Sing, E-mail: psleung@cuhk.edu.hk [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China)

2012-07-01

6

Mouse granzyme A induces a novel death with writhing morphology that is mechanistically distinct from granzyme B-induced apoptosis  

PubMed Central

Human and mouse granzyme (Gzm)B both induce target cell apoptosis in concert with pore-forming perforin (Pfp); however the mechanisms by which other Gzms induce non-apoptotic death remain controversial and poorly characterised. We used timelapse microscopy to document, quantitatively and in real time, the death of target cells exposed to primary natural killer (NK) cells from mice deficient in key Gzms. We found that in the vast majority of cases, NK cells from wild-type mice induced classic apoptosis. However, NK cells from syngeneic Gzm B-deficient mice induced a novel form of cell death characterised by slower kinetics and a pronounced, writhing, ‘worm-like' morphology. Dying cells initially contracted but did not undergo membrane blebbing, and annexin-V staining was delayed until the onset of secondary necrosis. As it is different from any cell death process previously reported, we tentatively termed this cell death ‘athetosis'. Two independent lines of evidence showed this alternate form of death was due to Gzm A: first, cell death was revealed in the absence of Gzm B, but was completely lost when the NK cells were deficient in both Gzm A and B; second, the athetotic morphology was precisely reproduced when recombinant mouse Gzm A was delivered by an otherwise innocuous dose of recombinant Pfp. Gzm A-mediated athetosis did not require caspase activation, early mitochondrial disruption or generation of reactive oxygen species, but did require an intact actin cytoskeleton and was abolished by latrunculin B and mycalolide B. This work defines an authentic role for mouse Gzm A in granule-induced cell death by cytotoxic lymphocytes. PMID:23744295

Susanto, O; Stewart, S E; Voskoboinik, I; Brasacchio, D; Hagn, M; Ellis, S; Asquith, S; Sedelies, K A; Bird, P I; Waterhouse, N J; Trapani, J A

2013-01-01

7

SPE 91413SPE 91413 Anangela Garcia  

E-print Network

Modeling System (NEMS) Energy Information Administration #12;SPE Eastern Regional Meeting Gas price (1 Regional Meeting #12;SPE Eastern Regional Meeting #12;SPE Eastern Regional Meeting Annual Energy Outlook (2025) EIA's National Energy Modeling System (NEMS) Annual Energy Outlook (2025) EIA's National Energy

Mohaghegh, Shahab

8

Ultraviolet-B-Induced Apoptosis of Keratinocytes: Evidence for Partial Involvement of Tumor Necrosis Factor-? in the Formation of Sunburn Cells  

Microsoft Academic Search

Irradiation with ultraviolet (UV) B radiation results in the formation of apoptotic keratinocytes called sunburn cells. Recently, it was demonstrated that keratinocytes can release tumor necrosis factor-? (TNF-?), which is known to cause apoptosis in particular cells. In addition, it has been shown that UVB light induces the release of TNF-? by keratinocytes and that keratinocytes express the 55-kD receptor

Agatha Schwarz; Ranjit Bhardwaj; Yoshinori Aragane; Karsten Mahnke; Helge Riemann; Dieter Metze; Thomas A. Luger; Thomas Schwarz

1995-01-01

9

Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells.  

PubMed

Pseudolaric acid B (PAB), a natural diterpene acid present in the traditional Chinese medicinal herb Tu-Jin-Pi, exerted anticancer effects on various cancer cells. However, the effect of PAB on DU145 cells, an in vitro model of hormone-refractory prostate cancer (HRPC), has not been reported previously. In the study, PAB significantly suppressed proliferation of DU145 cells in a dose-dependent manner without obvious cytotoxicity. IC(50) values of 0.89 ± 0.18 and 0.76 ± 0.15 ?M at 48h was determined by Cell counting kit (CCK-8) assay and clone formation assay, respectively. PAB also induced DU145 cells apoptosis as confirmed by typical morphological changes and Annexin V-FITC staining. Furthermore, we demonstrated that PAB caused a concentration-dependent elevation of reactive oxygen species (ROS) level in DU145 cells, and N-acetyl-l-cysteine (NAC, a well-known ROS scavenger) could block PAB-induced ROS generation and apoptosis. Western blotting and/or caspase activity data indicated that PAB downregulated anti-apoptotic Bcl-2 protein and activated caspase-9 and caspase-3, which were largely rescued by NAC or MG-132 (proteasome inhibitor). Taken together, these findings provide the first evidence that PAB may inhibit growth of HRPC DU145 cells and induce apoptosis through ROS generation and Bcl-2 degradation via the activation of the ubiquitin-proteasome pathway. PMID:22388098

Zhao, Dandan; Lin, Feng; Wu, Xingde; Zhao, Qinshi; Zhao, Binjiahui; Lin, Ping; Zhang, Yanlong; Yu, Xiaoguang

2012-06-01

10

Apoptosis  

NSDL National Science Digital Library

This Teaching Resource provides lecture notes and slides for a class covering apoptosis and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture contains a discussion of the apoptosis genes in Caenorhabditis elegans, the properties of the caspases, the major components of the extrinsic apoptotic signal transduction pathway, and the major components of the intrinsic (mitochondrial) apoptotic pathway.

Sherwin Wilk (Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine;)

2005-05-24

11

PEM/SPE fuel cell  

DOEpatents

A PEM/SPE fuel cell including a membrane-electrode assembly (MEA) having a plurality of oriented filament embedded the face thereof for supporting the MEA and conducting current therefrom to contiguous electrode plates.

Grot, Stephen Andreas (Henrietta, NY)

1998-01-01

12

PEM/SPE fuel cell  

DOEpatents

A PEM/SPE fuel cell is described including a membrane-electrode assembly (MEA) having a plurality of oriented filament embedded the face thereof for supporting the MEA and conducting current therefrom to contiguous electrode plates. 4 figs.

Grot, S.A.

1998-01-13

13

A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia.  

PubMed

p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML. PMID:25387678

Xia, D Y; Liu, L; Hao, M W; Liu, Q; Chen, R A; Liang, Y M

2014-12-01

14

Current SPE Hydrodynamic Modeling and Path Forward  

SciTech Connect

Extensive work has been conducted on SPE analysis efforts: Fault effects Non-uniform weathered layer analysis MUNROU: material library incorporation, parallelization, and development of non-locking tets Development of a unique continuum-based-visco-plastic strain-rate-dependent material model With corrected SPE data path is now set for a multipronged approach to fully understand experimental series shot effects.

Knight, Earl E. [Los Alamos National Laboratory; Rougier, Esteban [Los Alamos National Laboratory

2012-08-14

15

Biological Response to SPE Exposures  

NASA Technical Reports Server (NTRS)

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left unquantified. In the present report we use the bioresponse model derived from a broad range of animal and human exposure data for evaluation of troop readiness in tactical nuclear warfare to evaluate the biological risk posed by the solar event of 4 August 1972. The astronaut blood forming organ (BFO) exposure in deep space would have been 2.2 Sv (1.6 Gy) in a space suit, 1.8 Sv (1.3 Gy) in an aluminum pressure vessel, and 0.7 Sv (0.5 Gy) in an equipment room compared to an X-ray mortality threshold of 1.5 Gy (assuming high dose rate). We find BFO dose rate effectiveness factors for this SPE on the order of 3 to 4, greatly reducing the mortality risks for this event. There is an approximate 3 percent chance that an even larger event may occur for which exposures could be 2-4 times higher. Assured survival of the astronaut requires added shelter shielding and a warning system for this event. The required mass of the shelter shield can be greatly reduced by using hydrogenous materials such as polymers, water, food, and other biological materials in its construction. Limitations of the current bioresponse model arise from the exposures taking place in the microgravity environment wherein the immune system is already challenged and the effective mortality threshold may be reduced by a factor of two. Such microgravity effects could greatly affect astronaut risks.

Wilson, J. W.; Cucinotta, F. A.; Kim, M.; Shinn, J. L.; Jones, T. D.; Chang, C. K.

2004-01-01

16

Nuclear factor-? B inducing kinase is required for graft-versus-host disease  

PubMed Central

Background Donor T lymphocytes are directly responsible for graft-versus-host disease. Molecules important in T-cell function may, therefore, be appropriate targets for graft-versus-host disease therapy and/or prophylaxis. Here we analyzed whether nuclear factor-? B inducing kinase might have a role in graft-versus-host disease. Design and Methods We studied the expression of nuclear factor-? B inducing kinase in human samples from patients with graft-versus-host disease. We also explored the effect of nuclear factor-? B inducing kinase in a murine model of graft-versus-host disease using donor cells from aly/aly mice (deficient in nuclear factor-? B inducing kinase) and C57BL/6 mice (control). Results We detected expression of nuclear factor-? B inducing kinase in T-lymphocytes in the pathological lesions of patients with acute graft-versus-host disease. Mice transplanted with aly/aly T lymphocytes did not develop graft-versus-host disease at all, while mice receiving C57BL/6 cells died of a lethal form of the disease. Deficiency of nuclear factor-? B inducing kinase did not affect the engrafting ability of donor T cells, but severely impaired their expansion capacity early after transplantation, and aly/aly T cells showed a higher proportion of apoptosis than did C57BL/6 T cells. Effector T lymphocytes were the T-cell subset most affected by nuclear factor-? B inducing kinase deficiency. We also detected lower amounts of inflammatory cytokines in the serum of mice receiving aly/aly T cells than in the serum of mice receiving C57BL/6 T cells. Conclusions Our results show that nuclear factor-? B inducing kinase has a role in graft-versus-host disease by maintaining the viability of activated alloreactive T lymphocytes. PMID:20823135

Sanchez-Valdepenas, Carmen; Casanova, Lucia; Colmenero, Isabel; Arriero, Mar; Gonzalez, Africa; Lozano, Nieves; Gonzalez-Vicent, Marta; Diaz, Miguel A.; Madero, Luis; Fresno, Manuel; Ramirez, Manuel

2010-01-01

17

Proceedings of the SPE California regional meeting  

SciTech Connect

This book contains the proceedings of the SPE California regional meetings. Topics covered include: selection of tools for stimulation in horizontal cased hole, appraisal of analytical steamflood models, studies of fracture induced during cyclic steam injection, and extended-reach drilling from platform Irene.

Not Available

1990-01-01

18

spe415-03 page 29 INTRODUCTION  

E-print Network

spe415-03 page 29 29 INTRODUCTION The history and dynamics of the Laurentide Ice Sheet (LIS) have of cosmogenic nuclides to Laurentide Ice Sheet history and dynamics Jason P. Briner Department of Geology and basal dynamics of the Laurentide Ice Sheet (LIS) during the last glacial cycle remain elusive

Briner, Jason P.

19

spe433-01 page 1 INTRODUCTION  

E-print Network

spe433-01 page 1 INTRODUCTION The reality of plate tectonics, as a description of relative motions that plate tectonics has operated in something like its present style for, at most, the past billion years, Driving mechanism and 3-D circulation of plate tectonics, in Sears, J.W., Harms, T.A., and Evenchick, C

Hamilton, Warren B.

20

SPE-169507-MS Artificial Intelligence (AI) Assisted History Matching  

E-print Network

SPE-169507-MS Artificial Intelligence (AI) Assisted History Matching Alireza Shahkarami, Shahab D Mining (AI&DM) are used to develop Surrogate Reservoir Model (SRM) for utilization as the engine to drive Intelligence, Surrogate Reservoir Model (SRM), AI Assisted History Matching #12;2 SPE SPE-169507-MS 1

Mohaghegh, Shahab

21

SPE water electrolyzers in support of the lunar outpost  

NASA Technical Reports Server (NTRS)

During the 1970s, the SPE water electrolyzer, which uses ion exchange membranes as its sole electrolyte, was developed for nuclear submarine metabolic oxygen production. These developments included SPE water electrolyzer operation at up to 3,000 psia and at current densities in excess of 1,000 amps per square foot. The SPE water electrolyzer system is now fully qualified for both the U.S. and U.K. Navies with tens of thousands of system hours accumulated at sea. During the 1980s, the basic SPE water electrolyzer cell structure developed for the Navies was incorporated into several demonstrations for NASA's Space Station Program. Among these were: the SPE regenerative fuel cell for electrical energy storage; the SPE water electrolyzer for metabolic oxygen production; and the high pressure SPE water electrolyzer for reboost propulsion reactant production. In the 1990s, one emphasis will be the development of SPE water electrolyzers for the Lunar Outposts Currently defined potential Lunar Outpost applications for the SPE water electrolyzer include: SPE water electrolyzers for metabolic oxygen and potable water production from reclaimed water; and SPE water electrolyzers operating at high pressure as part of stationary and mobile surface energy storage systems.

Mcelroy, J. F.

1992-01-01

22

Virtual Measurement in Pipes, Part 2: Liquid Holdup and Flow Pattern Correlations J. Ternyik, IV, SPE, H.I. Bilgesu, SPE, S. Mohaghegh, SPE, West Virginia U.  

E-print Network

of Petroleum Engineers, Inc. This paper was prepared for presentation at the SPE Eastern Regional Conference(s). Contents of the paper have not been reviewed by the Society of Petroleum Engineers and are subject of the Society of Petroleum Engineers, its officers, or members. Papers presented at SPE meetings are subject

Mohaghegh, Shahab

23

SPE dose prediction using locally weighted regression.  

PubMed

When astronauts are outside earth's protective magnetosphere, they are subject to large radiation doses resulting from solar particle events (SPEs). The total dose received from a major SPE in deep space could cause severe radiation poisoning. The dose is usually received over a 20-40 h time interval but the event's effects may be mitigated with an early warning system. This paper presents a method to predict the total dose early in the event. It uses a locally weighted regression model, which is easier to train and provides predictions as accurate as neural network models previously used. PMID:16604634

Hines, J W; Townsend, L W; Nichols, T F

2005-01-01

24

SPE-163690-MS Synthetic, Geomechanical Logs for Marcellus Shale  

E-print Network

. Mohaghegh, SPE, S. Esmaili, SPE, West Virginia University Copyright 2013, Society of Petroleum Engineers have not been reviewed by the Society of Petroleum Engineers and are subject to correction by the author(s). The material does not necessarily reflect any position of the Society of Petroleum Engineers

Mohaghegh, Shahab

25

SPE propulsion electrolyzer for NASA's integrated propulsion test article  

NASA Technical Reports Server (NTRS)

Hamilton Standard has delivered a 3000 PSI SPE Propulsion Electrolyzer Stack and Special Test Fixture to the NASA Lyndon B. Johnson Space Center (JSC) Integrated Propulsion Test Article (IPTA) program in June 1990, per contract NAS9-18030. This prototype unit demonstrates the feasibility of SPE-high pressure water electrolysis for future space applications such as Space Station propulsion and Lunar/Mars energy storage. The SPE-Propulsion Electrolyzer has met or exceeded all IPTA program goals. It continues to function as the primary hydrogen and oxygen source for the IPTA test bed at the NASA/JSC Propulsion and Power Division Thermochemical Test Branch.

1991-01-01

26

SPE propulsion electrolyzer for NASA's integrated propulsion test article  

NASA Astrophysics Data System (ADS)

Hamilton Standard has delivered a 3000 PSI SPE Propulsion Electrolyzer Stack and Special Test Fixture to the NASA Lyndon B. Johnson Space Center (JSC) Integrated Propulsion Test Article (IPTA) program in June 1990, per contract NAS9-18030. This prototype unit demonstrates the feasibility of SPE-high pressure water electrolysis for future space applications such as Space Station propulsion and Lunar/Mars energy storage. The SPE-Propulsion Electrolyzer has met or exceeded all IPTA program goals. It continues to function as the primary hydrogen and oxygen source for the IPTA test bed at the NASA/JSC Propulsion and Power Division Thermochemical Test Branch.

1991-08-01

27

SPE (tm) regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications  

NASA Technical Reports Server (NTRS)

Viewgraphs on SPE regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications are presented. Topics covered include: hydrogen-oxygen regenerative fuel cell energy storage system; electrochemical cell reactions; SPE cell voltage stability; passive water removal SPE fuel cell; fuel cell performance; SPE water electrolyzers; hydrophobic oxygen phase separator; hydrophilic/electrochemical hydrogen phase separator; and unitized regenerative fuel cell.

Mcelroy, J. F.

1990-01-01

28

Enniatin B-induced cell death and inflammatory responses in RAW 267.4 murine macrophages  

SciTech Connect

The mycotoxin enniatin B (EnnB) is predominantly produced by species of the Fusarium genera, and often found in grain. The cytotoxic effect of EnnB has been suggested to be related to its ability to form ionophores in cell membranes. The present study examines the effects of EnnB on cell death, differentiation, proliferation and pro-inflammatory responses in the murine monocyte–macrophage cell line RAW 264.7. Exposure to EnnB for 24 h caused an accumulation of cells in the G0/G1-phase with a corresponding decrease in cyclin D1. This cell cycle-arrest was possibly also linked to the reduced cellular ability to capture and internalize receptors as illustrated by the lipid marker ganglioside GM1. EnnB also increased the number of apoptotic, early apoptotic and necrotic cells, as well as cells with elongated spindle-like morphology. The Neutral Red assay indicated that EnnB induced lysosomal damage; supported by transmission electron microscopy (TEM) showing accumulation of lipids inside the lysosomes forming lamellar structures/myelin bodies. Enhanced levels of activated caspase-1 were observed after EnnB exposure and the caspase-1 specific inhibitor ZYVAD-FMK reduced EnnB-induced apoptosis. Moreover, EnnB increased the release of interleukin-1beta (IL-1?) in cells primed with lipopolysaccharide (LPS), and this response was reduced by both ZYVAD-FMK and the cathepsin B inhibitor CA-074Me. In conclusion, EnnB was found to induce cell cycle arrest, cell death and inflammation. Caspase-1 appeared to be involved in the apoptosis and release of IL-1? and possibly activation of the inflammasome through lysosomal damage and leakage of cathepsin B. -- Highlights: ? The mycotoxin EnnB induced cell cycle arrest, cell death and inflammation. ? The G0/G1-arrest was linked to a reduced ability to internalize receptors. ? EnnB caused lysosomal damage, leakage of cathepsin B and caspase-1 cleavage. ? Caspase-1 was partly involved in both apoptosis and release of IL-1?. ? There was a synergistic action between EnnB and bacterial LPS.

Gammelsrud, A. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway) [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Solhaug, A. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway)] [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Dendelé, B. [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France)] [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France); Sandberg, W.J. [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)] [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Ivanova, L. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway)] [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Kocbach Bølling, A. [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)] [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Lagadic-Gossmann, D. [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France)] [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France); Refsnes, M.; Becher, R. [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)] [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Eriksen, G. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway)] [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Holme, J.A., E-mail: jorn.holme@fhi.no [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)

2012-05-15

29

Fast Track Analysis of Shale Numerical Models A. Kalantari-Dahaghi ,SPE, S. Esmaili, SPE, West Virginia University, S.D. Mohaghegh, SPE, Intelligent Solution  

E-print Network

Copyright 2012, Society of Petroleum Engineers This paper was prepared for presentation at the SPE Canadian of Petroleum Engineers and are subject to correction by the author(s). The material does not necessarily reflect any position of the Society of Petroleum Engineers, its officers, or members. Electronic

Mohaghegh, Shahab

30

Assay development for the discovery of semaphorin 3B inducing agents from natural product sources.  

PubMed

Semaphorins are a class of membrane-bound and secreted proteins. They have been found to regulate basic cell functions such as axonal growth cone guidance and recent studies have focused on their effect on tumor progression. Semaphorin 3B (Sema3B) particularly is a secreted protein that has been known to modulate proliferation and apoptosis, processes that are critical for tumor progression and development. In spite of its importance, there is yet no high-throughput screening assay available to detect or quantify the expression of Sema3B for natural product anticancer drug discovery purposes. Therefore, the development of a new high-throughput bioassay for the discovery of Sema3B inducing agents from natural product sources is described herein. A wide variety of pure compounds and extracts from plants and microorganisms has been found suitable for screening using this Sema3B assay to detect and quantify the effect of Sema3B inducing agents and thereby identify new selective bioactive Sema3B lead compounds for anticancer drug discovery and development. Also, this new bioassay procedure is based on a high-throughput platform using an enzyme-linked immunosorbent assay that involves the optimization of sensitivity and selectivity levels as well as accuracy, reproducibility, robustness, and cost effectiveness. PMID:25016954

Yong, Yeonjoong; Pan, Li; Ren, Yulin; Fatima, Nighat; Ahmed, Safia; Chang, Leng Chee; Zhang, Xiaoli; Kinghorn, A Douglas; Swanson, Steven M; Carcache de Blanco, Esperanza J

2014-10-01

31

Proceedings of the 1990 SPE annual technical conference and exhibition  

SciTech Connect

This book contains the proceedings of the 1990 SPE Annual Technical Conference. Included in this volume are the following papers: Testing and interpretation of injection wells using rate and pressure data, Fractured reservoir characterization through injection falloff and flowback tests, Advances in practical well test analysis.

Not Available

1990-01-01

32

An improved SPE method for fractionation and identification of phospholipids.  

PubMed

This work reports an efficient and universal SPE method developed for separation and identification of phospholipids derived from complex biological samples. For the separation step, sequential combination of silica gel-aminopropyl-silica gel SPE cartridges is applied. This setup enables separation of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, phosphatidylserine, cardiolipin, and sphingomyelin into four fractions according to the polarity of their headgroups. Sample acquisition of the SPE fractions is performed by a high-resolution LC-MS system consisting of a hybrid linear IT Fourier transform ion cyclotron resonance mass spectrometer coupled to RP-HPLC. The unequivocal advantage of our SPE sample preparation setup is avoidance of analyte peak overlapping in the determination step done by RP-HPLC. Overlapping phospholipid signals would otherwise exert adverse ion suppression effects. An additional benefit of this method is the elimination of polar and nonpolar (e.g. neutral lipids) contaminants from the phospholipid fractions, which highly reduces contamination of the LC-MS system. The method was validated with fermentation samples of organic waste, where 78 distinct phospholipid and sphingomyelin species belonging to six lipid classes were successfully identified. PMID:23349108

Fauland, Alexander; Trötzmüller, Martin; Eberl, Anita; Afiuni-Zadeh, Somaieh; Köfeler, Harald; Guo, Xinghua; Lankmayr, Ernst

2013-02-01

33

The sandbar shark, Carcharhinus plumbeus, is a large, coastal spe-  

E-print Network

387 The sandbar shark, Carcharhinus plumbeus, is a large, coastal spe- cies of the western north (Bigelow and Schroeder, 1948; Springer, 1960). Sandbar sharks are targeted by commercial fisher- ies and account for up to 60% of the large coastal shark landings in U.S. southern waters (NMFS, 1993). Adults

34

spe393-13 page 359 Geological Society of America  

E-print Network

spe393-13 page 359 359 Geological Society of America Special Paper 393 2005 Climatic and tectonic controls on Jurassic intra-arc basins related to northward drift of North America Cathy J. Busby in a releasing geometry relative to paleo-Pacific­North America plate motion. We hypothesize that strike

Busby, Cathy

35

CFE/SPE/RED 600 Literacy, Disability, & Inclusion  

E-print Network

1 CFE/SPE/RED 600 Literacy, Disability, & Inclusion May Semester, 2005 Instructor: Chris Kliewer Course, we will examine the Cultural Context of Literacy, Disability, and Inclusion. Again, this does. To struggle with #12;2 aspects of literacy often results in segregation from the literate community. In turn

Mather, Patrick T.

36

Proceedings of the 1991 SPE gas technology symposium  

SciTech Connect

This book contains the proceedings of the 1991 SPE Gas Technology Symposium. Included are the following papers: Maximizing gas recovery from strong water-drive reservoirs, Measurement of coal cleat porosity and relative permeability characteristics, recent developments in gas dehydration and hydrate inhibition.

Not Available

1991-01-01

37

WestVirginiaUniversity SPE 65675 Reservoir Characterization  

E-print Network

Approach A CB y z Alignment along B0 Tipping Dephasing x #12;WestVirginiaUniversity SPE 65675 METHODOLOGY · No Radioactive Sources · Used in Horizontal or Vertical Wells · Used in a majority of muds · COST · High Salinity

Mohaghegh, Shahab

38

Down-Regulation of p63 Is Required for Epidermal UV-B-induced Apoptosis  

Microsoft Academic Search

In the epidermis, p53 plays an important role in UV-B protection that led us to examine the role, if any, that p63, a p53 homologue highly expressed in the basal layer of the epidermis, might play in the epidermal UV-B response. One p63 isoform, DNp63a, decreased dramatically in normal keratinocytes or newborn epidermis at both the protein and RNA levels

Kristin M. Liefer; Maranke I. Koster; Xiao-Jing Wang; Annie Yang; Frank McKeon; Dennis R. Roop

2000-01-01

39

Exact Solutions in a Model of Vertical Gas Migration Dmitriy B. Silin, SPE, Lawrence Berkeley National Laboratory / UC Berkeley; Tad W. Patzek, SPE,  

E-print Network

SPE 103145 Exact Solutions in a Model of Vertical Gas Migration Dmitriy B. Silin, SPE, Lawrence storage formation. We seek exact solutions in a model of gas flow driven by a combination of buoyancy of the processes lead to different time scal- ing and different types of solutions. In the case of a thin tight

Patzek, Tadeusz W.

40

SPE OBOGS: On-board Oxygen Generating System  

NASA Technical Reports Server (NTRS)

Regulations require oxygen usage by commercial airliners during check out and during certain aircraft configurations. This oxygen is drawn from a high pressure on-board cylinder storage system. In a typical aircraft, oxygen cylinder removal for oxygen ground servicing is conducted every 4 to 6 weeks. In the early 1990's, it was recognized that an on-board oxygen generating system (OBOGS) could provide an economic advantage for the airlines. An in-flight service evaluation (ISE) of the SPE-OBOGS by United Technologies Corporate is in the planning stage.

Smith, William F.; McElroy, James F.

1996-01-01

41

NEAR FIELD MODELING OF SPE1 EXPERIMENT AND PREDICTION OF THE SECOND SOURCE PHYSICS EXPERIMENTS (SPE2)  

SciTech Connect

Motion along joints and fractures in the rock has been proposed as one of the sources of near-source shear wave generation, and demonstrating the validity of this hypothesis is a focal scientific objective of the source physics experimental campaign in the Climax Stock granitic outcrop. A modeling effort has been undertaken by LLNL to complement the experimental campaign, and over the long term provide a validated computation capability for the nuclear explosion monitoring community. The approach involves performing the near-field nonlinear modeling with hydrodynamic codes (e.g., GEODYN, GEODYN-L), and the far-field seismic propagation with an elastic wave propagation code (e.g., WPP). the codes will be coupled together to provide a comprehensive source-to-sensor modeling capability. The technical approach involves pre-test predictions of each of the SPE experiments using their state of the art modeling capabilities, followed by code improvements to alleviate deficiencies identified in the pre-test predictions. This spiral development cycle wherein simulations are used to guide experimental design and the data from the experiment used to improve the models is the most effective approach to enable a transition from the descriptive phenomenological models in current use to the predictive, hybrid physics models needed for a science-based modeling capability for nuclear explosion monitoring. The objective of this report is to describe initial results of non-linear motion predictions of the first two SPE shots in the Climax Stock: a 220-lb shot at a depth of 180 ft (SPE No.1), and a 2570-lb shot at a depth of 150 ft (SPE No.2). The simulations were performed using the LLNL ensemble granite model, a model developed to match velocity and displacement attenuation from HARDHAT, PILE DRIVER, and SHOAL, as well as Russian and French nuclear test data in granitic rocks. This model represents the state of the art modeling capabilities as they existed when the SPE campaign was launched in 2010, and the simulation results presented here will establish a baseline that will be used for gauging progress as planned modeling improvements are implemented during the remainder of the SPE program. The initial simulations were performed under 2D axisymmetric conditions assuming the geologic medium to be a homogeneous half space. However, logging data obtained from the emplacement hole reveal two major faults that intersect the borehole at two different depth intervals (NSTec report, 2011) and four major joint sets. To evaluate the effect of these discrete structures on the wave forms generated they have performed 2D and 3D analysis with a Lagrangian hydrocode, GEODYN-L that shares the same material models with GEODYN but can explicitly take joints and fault into consideration. They discuss results obtained using these two different approaches in this report.

Antoun, T; Xu, H; Vorobiev, O; Lomov, I

2011-10-20

42

SchlumbergerPrivate A.Kalantari-Dahaghi, S.D.Mohaghegh,SPE,  

E-print Network

for Sensitivity Study of Shale Gas Reservoir SPE 141058 SPE 2011 Production and Operation Symposium Oklahoma #12;Objective · Integrated workflow to capturing the essential characteristics of shale gas reservoirs · Development of Single well Shale Surrogate reservoir model (S3) #12;Introduction · Shale gas in the United

Mohaghegh, Shahab

43

SOCIAL WORK SPE/MHLTH Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/MHLTH Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ from the School of Social Work or other graduate level courses [Students with no Academic Sub Plan] RQ below has not been used toward specific degree course (Make no exceptions here) #12;SOCIAL WORK SPE

Shyy, Wei

44

SOCIAL WORK SPE/AG Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/AG Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ of Social Work or other graduate level courses [Students with no Academic Sub Plan] RQ 2285 Courses Not Used toward specific degree course (Make no exceptions here) #12;SOCIAL WORK SPE/AG Plan Requirements Campus

Shyy, Wei

45

SOCIAL WORK SPE/HLTH Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/HLTH Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ toward specific degree course (Make no exceptions here) #12;SOCIAL WORK SPE/HLTH Plan Requirements Campus Minimum three units from the School of Social Work or other graduate level courses [Academic Sub Plan

Shyy, Wei

46

spe-12 encodes a sperm cell surface protein that promotes spermiogenesis in Caenorhabditis elegans.  

PubMed Central

During spermiogenesis, Caenorhabditis elegans spermatids activate and mature into crawling spermatozoa without synthesizing new proteins. Mutations in the spe-12 gene block spermatid activation, rendering normally self-fertile hermaphrodites sterile. Mutant males, however, are fertile. Surprisingly, when mutant hermaphrodites mate with a male, their self-spermatids activate and form functional spermatozoa, presumably due to contact with male seminal fluid. Here we show that, in addition to its essential role in normal activation of hermaphrodite-derived spermatids, SPE-12 also plays a supplementary but nonessential role in mating-induced activation. We have identified the spe-12 gene, which encodes a novel protein containing a single transmembrane domain. spe-12 mRNA is expressed in the sperm-producing germ line and the protein localizes to the spermatid cell surface. We propose that SPE-12 functions downstream of both hermaphrodite- and male-derived activation signals in a spermatid signaling pathway that initiates spermiogenesis. PMID:10224255

Nance, J; Minniti, A N; Sadler, C; Ward, S

1999-01-01

47

Mass distribution in 11B induced fission of 232Th  

NASA Astrophysics Data System (ADS)

Formation cross sections of several fission products have been determined using recoil catcher technique followed by ?-ray spectrometry in 11B induced fission of 232Th at Elab=72, 60, and 55 MeV. The data show significant admixture of fission from compound nucleus formed by complete fusion as well as targetlike nuclei formed by transfer reaction. Mass distributions for both the fissioning systems have been obtained using the systematics of charge distribution in low and medium energy fission. The mass distribution for complete fusion fission is broad, Gaussian whereas it is asymmetric for transfer induced fission. The evaporation residue cross sections of targetlike nuclei formed in 232Th(11B, 10Be)233Pa reaction were also measured. The measured evaporation residue cross sections and the decay probabilities of targetlike nucleus 233Pa, calculated by the PACE2 code have been used to estimate the proton transfer fission cross sections which were found to be negligible compared to the total transfer cross section for all the projectile energies used. The transfer fission cross section is dominated by alpha transfer fission as inferred by measured forward to backward ratios for several fission products as well as Qgg systematics for the probable transfer reactions. The proportion of transfer fission cross section to the total fission cross section was 15, 17, and 22 % at projectile energies of 72, 60, and 55 MeV, respectively.

Gubbi, G. K.; Goswami, A.; Tomar, B. S.; Ramaswami, A.; Reddy, A. V. R.; Burte, P. P.; Manohar, S. B.; John, B.

1999-06-01

48

SpeCond: a method to detect condition-specific gene expression.  

PubMed

Transcriptomic studies routinely measure expression levels across numerous conditions. These datasets allow identification of genes that are specifically expressed in a small number of conditions. However, there are currently no statistically robust methods for identifying such genes. Here we present SpeCond, a method to detect condition-specific genes that outperforms alternative approaches. We apply the method to a dataset of 32 human tissues to determine 2,673 specifically expressed genes. An implementation of SpeCond is freely available as a Bioconductor package at http://www.bioconductor.org/packages/release/bioc/html/SpeCond.html. PMID:22008066

Cavalli, Florence M G; Bourgon, Richard; Huber, Wolfgang; Vaquerizas, Juan M; Luscombe, Nicholas M

2011-01-01

49

SpeCond: a method to detect condition-specific gene expression  

PubMed Central

Transcriptomic studies routinely measure expression levels across numerous conditions. These datasets allow identification of genes that are specifically expressed in a small number of conditions. However, there are currently no statistically robust methods for identifying such genes. Here we present SpeCond, a method to detect condition-specific genes that outperforms alternative approaches. We apply the method to a dataset of 32 human tissues to determine 2,673 specifically expressed genes. An implementation of SpeCond is freely available as a Bioconductor package at http://www.bioconductor.org/packages/release/bioc/html/SpeCond.html. PMID:22008066

2011-01-01

50

Apoptosis and Free Radicals  

Microsoft Academic Search

Free radicals that appear during physiological processes may lead to apoptosis in some pathological conditions when antioxidant capacity of the tissue is surpassed. Additionally, free radicals are involved in the control of apoptosis; antioxidant agents suppress apoptosis induced by a variety of stimuli. The possibility that apoptosis is regulated by modulation of the levels of free radicals is discussed.

Irina Stoian; Andra Oros; Elena Moldoveanu

1996-01-01

51

NF?B induces overexpression of bovine FcRn  

PubMed Central

Among the many functions of the neonatal Fc receptor (FcRn) for IgG, it binds to IgG-opsonized antigen complexes and propagates their traffic into lysosomes where antigen processing occurs. We previously reported that transgenic (Tg) mice and rabbits that carry multiple copies and overexpress FcRn have augmented humoral immune responses. Nuclear factor-kappa B (NF?B) is a critical molecule in the signaling cascade in the immune response. NF?B induces human FcRn expression and our previous in silico analysis suggested NF?B binding sites in the promoter region of the bovine (b) FcRn ?-chain gene (FCGRT). Here, we report the identification of three NF?B transcription binding sites in the promoter region of this gene using luciferase reporter gene technology, electromobility shift assay and supershift analysis. Stimulation of primary bovine endothelial cells with the Toll-like receptor-4 ligand lipopolysaccharide (LPS), which mediates its effect via NF?B, resulted in rapid upregulation of the bFcRn expression and a control gene, bovine E-selectin. This rapid bFcRn gene induction was also observed in the spleen of bFcRn Tg mice treated with intraperitoneally injected LPS, analyzed by northern blot analysis. Finally, NF?B-mediated bFcRn upregulation was confirmed at the protein level in macrophages isolated from the bFcRn Tg mice using flow cytometry with a newly developed FcRn specific monoclonal antibody that does not cross-react with the mouse FcRn. We conclude that NF?B regulates bFcRn expression and thus optimizes its functions, e.g., in the professional antigen presenting cells, and contributes to the much augmented humoral immune response in the bFcRn Tg mice. PMID:24492342

Cervenak, Judit; Doleschall, Marton; Bender, Balazs; Mayer, Balazs; Schneider, Zita; Doleschall, Zoltan; Zhao, Yaofeng; Bosze, Zsuzsanna; Hammarstrom, Lennart; Oster, Wolfgang; Kacskovics, Imre

2013-01-01

52

Neuropeptide B Induces Slow Wave Sleep in Mice  

PubMed Central

Study Objective: Neuropeptide B (NPB) and neuropeptide W (NPW) are two recently identified neuropeptides that act as endogenous ligands to orphan G protein coupled receptors, GPR7 and GPR8. In rodents, the GPR8 ortholog is absent and both NPB and NPW function exclusively through GPR7. Although NPB and NPW are implicated in the regulation of feeding behavior, endocrine function, and pain sensation, their physiological role is incompletely understood. Design: NPB or saline was administered into the lateral ventricle of mice during both the light and dark periods. In separate experiments, spontaneous locomotor activity or EEG and EMG were recorded after intracerebroventricular (i.c.v). injection. To confirm the involvement of GPR7 in NPB-induced responses, GPR7 knockout mice were also subjected to i.c.v. injections. Measurements and Results: NPB injections reduced locomotor activity during the dark period, but not during the light period. EEG and EMG recordings in freely moving mice revealed that NPB injection decreased the time spent in the waking state and increased the time spent in slow wave sleep (SWS) during the dark period. The time spent in paradoxical sleep was unaffected. The spectral power of NPB-induced SWS was indistinguishable from that of physiological SWS. The NPB-induced increase in SWS was not observed in GPR7 knockout mice. Conclusion: These results suggest that NPB induced physiological SWS through GPR7 and that NPB and GPR7 may have a role in modulating the occurrence of sleep and wakefulness. Citation: Hirashima N; Tsunematsu T; Ichiki K; Tanaka H; Kilduff TS; Yamanaka A. Neuropeptide B induces slow wave sleep in mice. SLEEP 2011;34(1):31-37. PMID:21203369

Hirashima, Noriko; Tsunematsu, Tomomi; Ichiki, Kanako; Tanaka, Hirokazu; Kilduff, Thomas S.; Yamanaka, Akihiro

2011-01-01

53

Pre-shot simulations of far-field ground motion for the Source Physics Experiment (SPE) Explosions at the Climax Stock, Nevada National Security Site: SPE2  

SciTech Connect

The Source Physics Experiment (SPE) is planning a 1000 kg (TNT equivalent) shot (SPE2) at the Nevada National Security Site (NNSS) in a granite borehole at a depth (canister centroid) of 45 meters. This shot follows an earlier shot of 100 kg in the same borehole at a depth 60 m. Surrounding the shotpoint is an extensive array of seismic sensors arrayed in 5 radial lines extending out 2 km to the north and east and approximately 10-15 to the south and west. Prior to SPE1, simulations using a finite difference code and a 3D numerical model based on the geologic setting were conducted, which predicted higher amplitudes to the south and east in the alluvium of Yucca Flat along with significant energy on the transverse components caused by scattering within the 3D volume along with some contribution by topographic scattering. Observations from the SPE1 shot largely confirmed these predictions although the ratio of transverse energy relative to the vertical and radial components was in general larger than predicted. A new set of simulations has been conducted for the upcoming SPE2 shot. These include improvements to the velocity model based on SPE1 observations as well as new capabilities added to the simulation code. The most significant is the addition of a new source model within the finite difference code by using the predicted ground velocities from a hydrodynamic code (GEODYN) as driving condition on the boundaries of a cube embedded within WPP which provides a more sophisticated source modeling capability linked directly to source site materials (e.g. granite) and type and size of source. Two sets of SPE2 simulations are conducted, one with a GEODYN source and 3D complex media (no topography node spacing of 5 m) and one with a standard isotropic pre-defined time function (3D complex media with topography, node spacing of 5 m). Results were provided as time series at specific points corresponding to sensor locations for both translational (x,y,z) and rotational components. Estimates of spectral scaling for SPE2 are provided using a modified version of the Mueller-Murphy model. An estimate of expected aftershock probabilities were also provided, based on the methodology of Ford and Walter, [2010].

Mellors, R J; Rodgers, A; Walter, W; Ford, S; Xu, H; Matzel, E; Myers, S; Petersson, N A; Sjogreen, B; Hauk, T; Wagoner, J

2011-10-18

54

SPE (trademark) Oxygen Generator Assembly (OGA). (Refurbishment of the technology demonstrator LFSPE oxygen generation subsystem)  

NASA Technical Reports Server (NTRS)

The SPE Oxygen Generator Assembly (OGA) has been modified to correct operational deficiencies present in the original system, and to effect changes to the system hardware and software such that its operating conditions are consistent with the latest configuration requirements for the International Space Station Alpha (ISSA). The effectiveness of these changes has recently been verified through a comprehensive test program which saw the SPE OGA operate for over 740 hours at various test conditions, including over 690 hours, or approximately 460 cycles, simulating the orbit of the space station. This report documents the changes made to the SPE OGA, presents and discusses the test results from the acceptance test program, and provides recommendations for additional development activities pertinent to evolution of the SPE OGA to a flight configuration. Copies of the test data from the acceptance test program are provided with this report on 3.5 inch diskettes in self-extracting archive files.

Roy, Robert J.

1995-01-01

55

SPE-HPTLC of procyanidins from the barks of different species and clones of Salix  

Microsoft Academic Search

A SPE-HPTLC method was developed for the qualitative and quantitative analysis of procyanidin B1 in willow barks. The chromatography was performed on HPTLC silica gel layer with the mobile phase chloroform–ethanol–formic acid (50:40:6v\\/v\\/v), in the Automatic Developing Chamber—ADC 2. The methanol extracts from willow barks were purified by SPE method on RP-18 silica gel columns with methanol–water (7:93v\\/v) as the

Loretta Pob?ocka-Olech; Miros?awa Krauze-Baranowska

2008-01-01

56

Using Spectral Losses to Map a Damage Zone for the Source Physics Experiments (SPE)  

NASA Astrophysics Data System (ADS)

We performed a series of cross-borehole seismic experiments in support of the Source Physics Experiments (SPE). These surveys, which were conducted in a granitic body using a sparker source and hydrophone string, were designed to image the damage zone from two underground explosions (SPE2 and SPE3). We present results here from a total of six boreholes (the explosive shot emplacement hole and 5 satellite holes, 20-35 meters away) where we found a marked loss of high frequency energy in ray paths traversing the region near the SPE explosions. Specifically, the frequencies above ~400 Hz were lost in a region centered around 45 meters depth, coincident with SPE2 and SPE3 shots. We further quantified these spectral losses, developed a map of where they occur, and evaluated the attenuation effects of raypath length (i.e. source-receiver offset). We attribute this severe attenuation to the inelastic damage (i.e. cracking and pulverizing) caused by the large chemical explosions and propose that frequency attenuation of this magnitude provides yet another tool for detecting the damage due to large underground explosions. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Knox, H. A.; Abbott, R. E.; Bonal, N.; Preston, L. A.

2013-12-01

57

Mathematical modeling of apoptosis  

PubMed Central

Apoptosis is a form of programmed cell death, which is fundamental to all multicellular organisms. Deregulation of apoptosis leads to a number of severe diseases including cancer. Apoptosis is initiated either by extrinsic signals via stimulation of receptors at the cellular surface or intrinsic signals, such as DNA damage or growth factor withdrawal. Apoptosis has been extensively studied using systems biology which substantially contributed to the understanding of this death signaling network. This review gives an overview of mathematical models of apoptosis and the potential of systems biology to contribute to the development of novel therapies for cancer or other apoptosis-related diseases. PMID:23803157

2013-01-01

58

Spacecraft Solar Particle Event (SPE) Shielding: Shielding Effectiveness as a Function of SPE Model as Determined with the FLUKA Radiation Transport Code  

Microsoft Academic Search

In the this paper, we report the results of modeling and simulation studies in which the radiation transport code FLUKA (FLUktuierende KAskade) is used to determine the changes in total ionizing dose (TID) and single-event effect (SEE) environments behind aluminum, polyethylene, carbon, and titanium shielding masses when the assumed form (i.e., Band or Exponential) of the solar particle event (SPE)

S. L. Koontz; W. A. Atwell; B. Reddell; K. Rojdev

2010-01-01

59

Intelligent Upscaling of Static and Dynamic Reservoir Properties V.Gholami, SPE and S.D.Mohaghegh, SPE, West Virginia University  

E-print Network

for presentation at the 2009 SPE Annual Technical Conference and Exhibition held in New Orleans, Louisiana, USA, 4 are concerned. The objective of this study is to develop a new upscaling methodology based on fuzzy set theory simulation studies and the new approach that is the subject of this study. By using the numerical reservoir

Mohaghegh, Shahab

60

Wentilactone B induces G2/M phase arrest and apoptosis via the Ras/Raf/MAPK signaling pathway in  

E-print Network

malignant tumor, and it is known to be resistant to conventional chemotherapy. Wentilactone B (WB both Ras and Raf activation, and transfection of cells with dominant-negative Ras (RasN17) abolished WB due to its resistance to chemotherapy and radiotherapy.4 Thus, novel therapeutic agents are urgently

Cai, Long

61

Cucurbitacin B Induced ATM-Mediated DNA Damage Causes G2/M Cell Cycle Arrest in a ROS-Dependent Manner  

PubMed Central

Cucurbitacins are a class of triterpenoids widely distributed in plant kingdom with potent anti-cancer activities both in vitro and in vivo by inducing cycle arrest, autophagy, and apoptosis. Cucurbitacin B (Cuc B), could induce S or G2/M cell cycle arrest in cancer cells while the detailed mechanisms remain to be clear. This study was designed to precisely dissect the signaling pathway(s) responsible for Cuc B induced cell cycle arrest in human lung adenocarcinoma epithelial A549 cells. We demonstrated that low concentrations of Cuc B dramatically induced G2/M phase arrest in A549 cells. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-? pathways, which could be reversed by ATM siRNA. Cuc B treatment also led to increased intracellular reactive oxygen species (ROS) formation, which was inhibited by N-acetyl-l-cysteine (NAC) pretreatment. Furthermore, NAC pretreatment inhibited Cuc B induced DNA damage and G2/M phase arrest. Taken together, these results suggested that Cuc B induces DNA damage in A549 cells mediated by increasing intracellular ROS formation, which lead to G2/M cell phase arrest through ATM-activated Chk1-Cdc25C-Cdk1 and p53-14-3-3-? parallel branches. These observations provide novel mechanisms and potential targets for better understanding of the anti-cancer mechanisms of cucurbitacins. PMID:24505404

Guo, Jiajie; Wu, Guosheng; Bao, Jiaolin; Hao, Wenhui; Lu, Jinjian; Chen, Xiuping

2014-01-01

62

Spacecraft Solar Particle Event (SPE) Shielding: Shielding Effectiveness as a Function of SPE model as Determined with the FLUKA Radiation Transport Code  

NASA Technical Reports Server (NTRS)

Analysis of both satellite and surface neutron monitor data demonstrate that the widely utilized Exponential model of solar particle event (SPE) proton kinetic energy spectra can seriously underestimate SPE proton flux, especially at the highest kinetic energies. The more recently developed Band model produces better agreement with neutron monitor data ground level events (GLEs) and is believed to be considerably more accurate at high kinetic energies. Here, we report the results of modeling and simulation studies in which the radiation transport code FLUKA (FLUktuierende KAskade) is used to determine the changes in total ionizing dose (TID) and single-event environments (SEE) behind aluminum, polyethylene, carbon, and titanium shielding masses when the assumed form (i. e., Band or Exponential) of the solar particle event (SPE) kinetic energy spectra is changed. FLUKA simulations have fully three dimensions with an isotropic particle flux incident on a concentric spherical shell shielding mass and detector structure. The effects are reported for both energetic primary protons penetrating the shield mass and secondary particle showers caused by energetic primary protons colliding with shielding mass nuclei. Our results, in agreement with previous studies, show that use of the Exponential form of the event

Koontz, Steve; Atwell, William; Reddell, Brandon; Rojdev, Kristina

2010-01-01

63

Signal transducer and activator of transcription-5 mediates neuronal apoptosis induced by inhibition of Rac GTPase activity.  

PubMed

In several neuronal cell types, the small GTPase Rac is essential for survival. We have shown previously that the Rho family GTPase inhibitor Clostridium difficile toxin B (ToxB) induces apoptosis in primary rat cerebellar granule neurons (CGNs) principally via inhibition of Rac GTPase function. In the present study, incubation with ToxB activated a proapoptotic Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and a pan-JAK inhibitor protected CGNs from Rac inhibition. STAT1 expression was induced by ToxB; however, CGNs from STAT1 knock-out mice succumbed to ToxB-induced apoptosis as readily as wild-type CGNs. STAT3 displayed enhanced tyrosine phosphorylation following treatment with ToxB, and a reputed inhibitor of STAT3, cucurbitacin (JSI-124), reduced CGN apoptosis. Unexpectedly, JSI-124 failed to block STAT3 phosphorylation, and CGNs were not protected from ToxB by other known STAT3 inhibitors. In contrast, STAT5A tyrosine phosphorylation induced by ToxB was suppressed by JSI-124. In addition, roscovitine similarly inhibited STAT5A phosphorylation and protected CGNs from ToxB-induced apoptosis. Consistent with these results, adenoviral infection with a dominant negative STAT5 mutant, but not wild-type STAT5, significantly decreased ToxB-induced apoptosis of CGNs. Finally, chromatin immunoprecipitation with a STAT5 antibody revealed increased STAT5 binding to the promoter region of prosurvival Bcl-xL. STAT5 was recruited to the Bcl-xL promoter region in a ToxB-dependent manner, and this DNA binding preceded Bcl-xL down-regulation, suggesting transcriptional repression. These data indicate that a novel JAK/STAT5 proapoptotic pathway significantly contributes to neuronal apoptosis induced by the inhibition of Rac GTPase. PMID:22378792

Stankiewicz, Trisha R; Loucks, F Alexandra; Schroeder, Emily K; Nevalainen, Marja T; Tyler, Kenneth L; Aktories, Klaus; Bouchard, Ron J; Linseman, Daniel A

2012-05-11

64

Evaluation of Al-doped SPE ultrashallow P+N Junctions for use as PNP SiGe HBT Emitters  

E-print Network

Evaluation of Al-doped SPE ultrashallow P+N Junctions for use as PNP SiGe HBT Emitters Yann Civale use of aluminum-mediated SPE silicon islands as ultrashallow Al-doped emitters in PNP SiGe HBTs-doped emitters display electrical properties similar to B-doped Si. The surface recombination velocity at the Al

Technische Universiteit Delft

65

Red drum, Sciaenops ocellatus, is an estuary-dependent marine spe-  

E-print Network

730 Red drum, Sciaenops ocellatus, is an estuary-dependent marine spe- cies found in coastal to Vera Cruz, Mexico (Yokel, 1966, 1980). Red drum are highly sought after as food and gamefish. Annual the sale of red drum was pro- hibited. Recreational fishing effort directed toward red drum in Florida has

66

SPE-153271-PP Semiautomatic, Semantic Assistance to Manual Curation of Data in Smart  

E-print Network

integration. Introduction Oil and gas organizations are in continuous pressure to investigate and employSPE-153271-PP Semiautomatic, Semantic Assistance to Manual Curation of Data in Smart Oil Fields with missing metadata, with terms from a domain ontology, which constantly evolves supervised by domain experts

Hwang, Kai

67

SPE -124703 Process for tracking the evolving perception of risk during CO2 storage  

E-print Network

for presentation at the 2009 SPE Offshore Europe Oil & Gas Conference & Exhibition held in Aberdeen, UK, 8 oil and gas reservoirs, and coal seams. While the technology for CCS already exists (e.g. Moritis discussion with experts. Regular updating of the register by experts is used to track changes

68

SPE-SAS-321 Estimating Layers Deliverability in Multi-Layered Gas Reservoirs Using  

E-print Network

Saudi Arabia Section Technical Symposium and Exhibition held in AlKhobar, Saudi Arabia, 8­11 April 2012. Several artificial intelligence methods such as ANN, GRNN, RBF, and SVM are presented in this study. #12;2 SPE-SAS-321 We have used two different data sets. The first one includes the inputs in their original

Hossain, M. Enamul

69

spe440-12 3rd pages The Geological Society of America  

E-print Network

spe440-12 3rd pages 249 The Geological Society of America Special Paper 440 2008 Plate tectonics and appear to be remarkably similar to predictions from a plate-tectonic conceptual model. Care- fully as old as ca. 3500 Ma. Keywords: plate tectonics, paleomagnetism, Precambrian, Archean, Proterozoic

70

SOCIAL WORK SPE/CSS Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/CSS Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ Minimum nine units from the School of Social Work or other graduate level courses [Students Effective FA02/1410 (09/03/2002) LN 0030 Minimum three units from the School of Social Work or other

Shyy, Wei

71

SOCIAL WORK SPE/CY Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/CY Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ Minimum nine units from the School of Social Work or other graduate level courses [Students02/1410 (09/03/2002) LN 0030 Minimum three units from the School of Social Work or other graduate

Shyy, Wei

72

STANDARD ADDITION METHOD FOR THE DETERMINATION OF1 PHARMACEUTICAL RESIDUES IN DRINKING WATER BY SPE-2  

E-print Network

STANDARD ADDITION METHOD FOR THE DETERMINATION OF1 PHARMACEUTICAL RESIDUES IN DRINKING WATER BY SPE compounds in drinking or waste22 water processes has become very popular in recent years. LC-MS/MS is a powerful23 analytical tool often used to determine pharmaceutical residues at trace level in water.24

Boyer, Edmond

73

24/02/2012 12:49SPE Projects, Facilities & Construction -CO2/Brine Surface Dissolution and Injection: CO2 Storage Enhancement Page 1 of 1http://www.spe.org/ejournals/jsp/journalapp.jsp?pageType=Preview&jid=EFC&pdfChronicleId=090147628022501b&mid=SPE-12471  

E-print Network

of Petroleum Engineers SPE Projects, Facilities & Construction Volume 6, Number 1, March 2011, pp. 41-53 SPE and Management 3.6 Research and Development Programs 4.1 Processing Systems and Design 4.1.1 Process Simulation 4 of Petroleum Engineers View full text Add To Cart ( 602 KB ) History Original manuscript received: 30 April

Haszeldine, Stuart

74

WINGS-SPE Spectroscopy in the WIde-field Nearby Galaxy-cluster Survey  

NASA Astrophysics Data System (ADS)

Aims: We present the results from a comprehensive spectroscopic survey of the WINGS (WIde-field Nearby Galaxy-cluster Survey) clusters, a program called WINGS-SPE. The WINGS-SPE sample consists of 48 clusters, 22 of which are in the southern sky and 26 in the north. The main goals of this spectroscopic survey are: (1) to study the dynamics and kinematics of the WINGS clusters and their constituent galaxies, (2) to explore the link between the spectral properties and the morphological evolution in different density environments and across a wide range of cluster X-ray luminosities and optical properties. Methods: Using multi-object fiber-fed spectrographs, we observed our sample of WINGS cluster galaxies at an intermediate resolution of 6-9 Å and, using a cross-correlation technique, we measured redshifts with a mean accuracy of ~45 km s-1. Results: We present redshift measurements for 6137 galaxies and their first analyses. Details of the spectroscopic observations are reported. The WINGS-SPE has ~30% overlap with previously published data sets, allowing us both to perform a complete comparison with the literature and to extend the catalogs. Conclusions: Using our redshifts, we calculate the velocity dispersion for all the clusters in the WINGS-SPE sample. We almost triple the number of member galaxies known in each cluster with respect to previous works. We also investigate the X-ray luminosity vs. velocity dispersion relation for our WINGS-SPE clusters, and find it to be consistent with the form Lx ? ?_v^4. Table 4, containing the complete redshift catalog, is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/495/707

Cava, A.; Bettoni, D.; Poggianti, B. M.; Couch, W. J.; Moles, M.; Varela, J.; Biviano, A.; D'Onofrio, M.; Dressler, A.; Fasano, G.; Fritz, J.; Kjærgaard, P.; Ramella, M.; Valentinuzzi, T.

2009-03-01

75

Apoptosis of Neutrophils  

Microsoft Academic Search

Regulation of the neutrophil life span by apoptosis provides a fine balance between their function as effector cells of host defense and a safe turnover of these potentially harmful cells. Alterations of neutrophil apoptosis are associated with a number of diseases. As do other cell types, neutrophils possess components of both extrinsic and intrinsic apoptotic routes. The intrinsic pathway of

N. A. Maianski; A. N. Maianski; T. W. Kuijpers; D. Roos

2004-01-01

76

Physics-based Reconstruction of Sedimentary Rocks Guodong Jin, UC Berkeley; Tad W. Patzek, SPE, UC Berkeley / Lawrence Berkeley National Laboratory; and Dmitry B. Silin,  

E-print Network

, SPE, UC Berkeley / Lawrence Berkeley National Laboratory; and Dmitry B. Silin, SPE, Lawrence Berkeley National Laboratory Copyright 2003, Society of Petroleum Engineers, Inc. This paper was preparedSPE 83587 Physics-based Reconstruction of Sedimentary Rocks Guodong Jin, UC Berkeley; Tad W. Patzek

Patzek, Tadeusz W.

77

Yersinia enterocolitica YopT and Clostridium difficile Toxin B Induce Expression of GILZ in Epithelial Cells  

PubMed Central

Glucocorticoid induced-leucine zipper (GILZ) has been shown to be induced in cells by different stimuli such as glucocorticoids, IL-10 or deprivation of IL-2. GILZ has anti-inflammatory properties and may be involved in signalling modulating apoptosis. Herein we demonstrate that wildtype Yersinia enterocolitica which carry the pYV plasmid upregulated GILZ mRNA levels and protein expression in epithelial cells. Infection of HeLa cells with different Yersinia mutant strains revealed that the protease activity of YopT, which cleaves the membrane-bound form of Rho GTPases was sufficient to induce GILZ expression. Similarly, Clostridium difficile toxin B, another bacterial inhibitor of Rho GTPases induced GILZ expression. YopT and toxin B both increased transcriptional activity of the GILZ promoter in HeLa cells. GILZ expression could not be linked to the inactivation of an individual Rho GTPase by these toxins. However, forced expression of RhoA and RhoB decreased basal GILZ promoter activity. Furthermore, MAPK activation proved necessary for profound GILZ induction by toxin B. Promoter studies and gel shift analyses defined binding of upstream stimulatory factor (USF) 1 and 2 to a canonical c-Myc binding site (E-box) in the GILZ promoter as a crucial step of its trans-activation. In addition we could show that USF-1 and USF-2 are essential for basal as well as toxin B induced GILZ expression. These findings define a novel way of GILZ promoter trans-activation mediated by bacterial toxins and differentiate it from those mediated by dexamethasone or deprivation of IL-2. PMID:22792400

Koberle, Martin; Goppel, David; Grandl, Tanja; Gaentzsch, Peer; Manncke, Birgit; Berchtold, Susanne; Muller, Steffen; Luscher, Bernhard; Asselin-Labat, Marie-Liesse; Pallardy, Marc; Sorg, Isabel; Langer, Simon; Barth, Holger; Zumbihl, Robert; Autenrieth, Ingo B.; Bohn, Erwin

2012-01-01

78

Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells.  

PubMed

The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis. PMID:21699495

Sun, Suxia; Li, Wenjun; Zhang, He; Zha, Longying; Xue, Yong; Wu, Xianbo; Zou, Fei

2012-02-01

79

c-Abl mediates endothelial apoptosis induced by inhibition of integrins ?v?3 and ?v?5 and by disruption of actin  

PubMed Central

Inhibition of integrins ?v?3 and ?v?5 in human brain microvascular endothelial cells (HBMECs) by the function-blocking peptide RGDfV induces loss of spreading on vitronectin, cell detachment, and apoptosis. We demonstrate that cell detachment is not required for apoptosis because plating on bovine serum albumin–blocked poly-L-lysine (allows attachment, but not integrin ligation and cell spreading) also induced apoptosis. Latrunculin B (LatB), which inhibits F-actin polymerization, induced transient loss of HBMEC spreading on vitronectin, but not their detachment, and induced apoptosis despite recovery of cell spreading. However, LatB did not cause apoptosis in 5 tumor cell lines. In HBMECs, both LatB and RGDfV induced transient Y412 and Y245 phosphorylation of endogenous c-Abl, a nonreceptor tyrosine kinase that reciprocally regulates F-actin. LatB also induced nuclear translocation of c-Abl in HBMECs. STI-571 (imatinib), a targeted therapy for BCR-ABL1+ leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. LatB-induced HBMEC apoptosis, and its inhibition by STI-571 also occurred in a 3-dimensional collagen model, supporting physiologic relevance. Last, siRNA to c-Abl (but not nonspecific siRNA) also inhibited RGDfV- and LatB-induced apoptosis. Thus, endogenous c-Abl mediates endothelial apoptosis induced by inhibition of integrins ?v?3/?v?5 or by LatB-induced disruption of F-actin. PMID:20124512

Xu, Jingying; Millard, Melissa; Ren, Xiuhai; Cox, Orla T.

2010-01-01

80

Hindlimb suspension and SPE-like radiation impairs clearance of bacterial infections.  

PubMed

A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health. PMID:24454913

Li, Minghong; Holmes, Veronica; Zhou, Yu; Ni, Houping; Sanzari, Jenine K; Kennedy, Ann R; Weissman, Drew

2014-01-01

81

SPE-HPTLC of procyanidins from the barks of different species and clones of Salix.  

PubMed

A SPE-HPTLC method was developed for the qualitative and quantitative analysis of procyanidin B(1) in willow barks. The chromatography was performed on HPTLC silica gel layer with the mobile phase chloroform-ethanol-formic acid (50:40:6 v/v/v), in the Automatic Developing Chamber-ADC 2. The methanol extracts from willow barks were purified by SPE method on RP-18 silica gel columns with methanol-water (7:93 v/v) as the eluent. The presence of procyanidin B(1) was revealed in the majority of investigated willow barks. The content of procyanidin B(1) varied from 0.26 mg/g in the extract of Salix purpurea clone 1067-2.24 mg/g in the extract of Salix alba clone 1100. The method was validated for linearity, precision, LOD, LOQ and repeatability. PMID:18639405

Pob?ocka-Olech, Loretta; Krauze-Baranowska, Miros?awa

2008-11-01

82

Hindlimb Suspension and SPE-Like Radiation Impairs Clearance of Bacterial Infections  

PubMed Central

A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health. PMID:24454913

Li, Minghong; Holmes, Veronica; Zhou, Yu; Ni, Houping; Sanzari, Jenine K.; Kennedy, Ann R.; Weissman, Drew

2014-01-01

83

Determination of antibiotic compounds in water by on-line SPE-LC\\/MSD  

Microsoft Academic Search

This study attempts to provide an improved approach for the analysis of antibiotics, which normally exist at low concentration in complex matrices such as receiving streams of wastewater treatment plant discharge. The analytical method developed in this study combines an existing pretreatment technique of solid-phase extraction (SPE) with liquid chromatography mass spectrometry (LC\\/MSD) through on-line connection. The on-line connection suppressed

Keun-Joo Choi; Sang-Goo Kim; Chang-won Kim; Seung-Hyun Kim

2007-01-01

84

Genetic and Molecular Characterization of the Caenorhabditis Elegans Spermatogenesis-Defective Gene Spe-17  

PubMed Central

Two self-sterile mutations that define the spermatogenesis-defective gene spe-17 have been analyzed. These mutations affect unc-22 and fail to complement each other for both Unc-22 and spermatogenesis defects. Both of these mutations are deficiencies (hcDf1 and hDf13) that affect more than one transcription unit. Genomic DNA adjacent to and including the region deleted by the smaller deficiency (hcDf1) has been sequenced and four mRNAs (including unc-22) have been localized to this sequenced region. The three non unc-22 mRNAs are shown to be sex-specific: a 1.2-kb mRNA that can be detected in sperm-free hermaphrodites and 1.2- and 0.56-kb mRNAs found in males. hDf13 deletes at least 55 kb of chromosome IV, including all of unc-22, both male-specific mRNAs and at least part of the female-specific mRNA. hcDf1, which is approximately 15.6 kb, deletes only the 5' end of unc-22 and the gene that encodes the 0.56-kb male-specific mRNA. The common defect that apparently accounts for the defective sperm in hcDf1 and hDf13 homozygotes is deletion of the spe-17 gene, which encodes the 0.56-kb mRNA. Strains carrying two copies of either deletion are self-fertile when they are transgenic for any of four extrachromosomal array that include spe-17. We have sequenced two spe-17 cDNAs, and the deduced 142 amino acid protein sequence is highly charged and rich in serine and threonine, but shows no significant homology to any previously determined protein sequence. PMID:8349108

L'Hernault, S. W.; Benian, G. M.; Emmons, R. B.

1993-01-01

85

Retention behaviour of some high-intensity sweeteners on different SPE sorbents  

Microsoft Academic Search

The objective of this paper is to provide information about application of solid-phase extraction (SPE) for isolation of nine high-intensity sweeteners (acesulfame-K, alitame, aspartame, cyclamate, dulcin, neotame, saccharin, sucralose and neohesperidin dihydrochalcone) from aqueous solutions. The influence of several types of LC–MS compatible buffers (different pH values and compositions) on their recovery has been studied and discussed. A number of

Agata Zygler; Andrzej Wasik; Jacek Namie?nik

2010-01-01

86

SolidPhase Extraction (SPE) and HPLC Analysis of Toxic Compounds and Comparison of SPE and Liquid-Liquid Extraction. I. Analysis of 4, 4?-Methyl-Enedianiline in Serum. II. Analysis of the Components of Dental Materials  

Microsoft Academic Search

In this paper, we discuss two subjects concerned with solid phase extraction (SPE) and HPLC analysis of toxic compounds eluted to serum from materials used for medical devices. SPE and liquid-liquid extraction for serum toxic compounds were compared. Firstly, an analysis of a toxic and carcinogenic compound, 4,4?-methylenedianiline (MDA), from polyurethane sterilized by gamma-ray irradiation was studied. Serum MDA was

H. Shintani

1992-01-01

87

Comparison of Radiation Transport Codes, HZETRN, HETC and FLUKA, Using the 1956 Webber SPE Spectrum  

NASA Technical Reports Server (NTRS)

Protection of astronauts and instrumentation from galactic cosmic rays (GCR) and solar particle events (SPE) in the harsh environment of space is of prime importance in the design of personal shielding, spacec raft, and mission planning. Early entry of radiation constraints into the design process enables optimal shielding strategies, but demands efficient and accurate tools that can be used by design engineers in every phase of an evolving space project. The radiation transport code , HZETRN, is an efficient tool for analyzing the shielding effectiveness of materials exposed to space radiation. In this paper, HZETRN is compared to the Monte Carlo codes HETC-HEDS and FLUKA, for a shield/target configuration comprised of a 20 g/sq cm Aluminum slab in front of a 30 g/cm^2 slab of water exposed to the February 1956 SPE, as mode led by the Webber spectrum. Neutron and proton fluence spectra, as well as dose and dose equivalent values, are compared at various depths in the water target. This study shows that there are many regions where HZETRN agrees with both HETC-HEDS and FLUKA for this shield/target configuration and the SPE environment. However, there are also regions where there are appreciable differences between the three computer c odes.

Heinbockel, John H.; Slaba, Tony C.; Blattnig, Steve R.; Tripathi, Ram K.; Townsend, Lawrence W.; Handler, Thomas; Gabriel, Tony A.; Pinsky, Lawrence S.; Reddell, Brandon; Clowdsley, Martha S.; Singleterry, Robert C.; Norbury, John W.; Badavi, Francis F.; Aghara, Sukesh K.

2009-01-01

88

Overview of passive Chemcatcher sampling with SPE pretreatment suitable for the analysis of NPEOs and NPs.  

PubMed

The European Union Water Framework Directive (WFD; 2000/60/EC) is an important piece of environmental legislation that protects rivers, lakes, coastal waters and groundwaters (EC 2000). The implementation of the WFD requires the establishment and use of novel and low-cost monitoring programmes, and several methods, e.g. passive sampling, have been developed to make the sampling process more representative compared to spot sampling. This review considers passive sampling methods focusing mainly on a passive sampler named Chemcatcher®, which has been used for monitoring several harmful compounds in aquatic environments. Also, the sample treatment and analysis of nonylphenol ethoxylates (NPEOs) and nonylphenol (NPs) from water using solid phase extraction (SPE) is briefly summarized. The procedure of Chemcatcher passive sampling is quite similar to that of the SPE extraction since it concentrates the studied compounds from water as well. After sampling, the accumulated substances are extracted from the receiving phase of the sampler. The concentrations of NPEOs and NPs are currently monitored by taking conventional spot samples; SPE can be successfully used as a pretreatment procedure. Chemcatcher® passive sampling technique is a simple and useful monitoring tool and can be applied to new chemicals, such as NPEOs and NPs in aquatic environments. PMID:22983602

Ahkola, Heidi; Herve, Sirpa; Knuutinen, Juha

2013-03-01

89

The Crystal Structure of Escherichia coli Spermidine Synthase SpeE Reveals a Unique Substrate-binding Pocket  

SciTech Connect

Polyamines are essential in all branches of life. Biosynthesis of spermidine, one of the most ubiquitous polyamines, is catalyzed by spermidine synthase (SpeE). Although the function of this enzyme from Escherichia coli has been thoroughly characterized, its structural details remain unknown. Here, we report the crystal structure of E. coli SpeE and study its interaction with the ligands by isothermal titration calorimetry and computational modelling. SpeE consists of two domains - a small N-terminal {beta}-strand domain, and a C-terminal catalytic domain that adopts a canonical methyltransferase (MTase) Rossmann fold. The protein forms a dimer in the crystal and in solution. Structural comparison of E. coli SpeE to its homologs reveals that it has a large and unique substrate-binding cleft that may account for its lower amine substrate specificity.

Zhou, X.; Chua, T; Tkaczuk, K; Bujnicki, J; Sivaraman, J

2010-01-01

90

Apoptosis in Melanoma  

Microsoft Academic Search

Apoptosis deficiency seems to be involved in the high resistance of melanoma to therapeutic treatment. This has come into\\u000a focus because the cytotoxic effects of chemotherapeutic agents via apoptosis are known. Extensive investigations have been\\u000a made analyzing the role of alterations in the apoptotic pathway in melanoma. The molecular changes affect antiapoptotic, as\\u000a well as proapoptotic, processes and survival signals

Heike Röckmann; Dirk Schadendorf

91

Apoptosis in SIV infection  

Microsoft Academic Search

Pathogenic human immunodeficiency virus (HIV)\\/Simian immunodeficiency virus (SIV) infection is associated with increased T-cell apoptosis. In marked contrast to HIV infection in humans and SIV infection in macaques, the SIV infection of natural host species is typically nonpathogenic despite high levels of viral replication. In these nonpathogenic primate models, no observation of T-cell apoptosis was observed, suggesting that either SIV

B Hurtrel; F Petit; D Arnoult; M Müller-Trutwin; G Silvestri; J Estaquier

2005-01-01

92

Signaling cascades of apoptosis  

Microsoft Academic Search

\\u000a Apoptosis, or programmed cell death, is the process which deletes cells from a population in a deliberate manner without eliciting\\u000a an immune response. This type of cell death maintains homeostasis and is central to the development, selection, and activity\\u000a of lymphocytes. Through apoptosis, host-reactive immune cells are eliminated during their development and activated cells\\u000a in the periphery are eliminated to

Cynthia L. Mann; John A. Cidlowski

93

Quantitative determination of oil films\\/slicks from water surfaces using a modified solid- phase extraction (SPE) sampling method  

Microsoft Academic Search

We have developed a procedure using solid-phase extraction (SPE) for the quantitative determination of oil films and slicks floating on water surfaces. During Phase One of this study, nine oil loadings (Exxon #6 fuel oil: 3 to 38 mg\\/cm2) were sub sampled with C18-SPE disks in replicates (n = 2-4) from the surface of 1L beakers. Sonication and accelerated solvent

P. Louchouarn; J. S. Bonner; P. Tissot; T. J. McDonald; C. Fuller

94

UV-B-induced plant stress as a possible cause of ten-year hare cycles  

Microsoft Academic Search

Predation has been assumed to be a necessary factor in the ten-year population cycle of the snowshoe hare (Lepus americanus) and Canadian lynx (Lynx canadensis). The UV-B-induced plant stress hypothesis, in contrast, predicts that hare performance, especially reproduction, is negatively related to sunspot numbers, because production of UV-B-protective phenolics in food plants in periods of low sunspot activity, when the

Vidar Selås

2006-01-01

95

NF-kappa B-inducing Kinase Activates IKK-alpha by Phosphorylation of Ser176  

Microsoft Academic Search

Activation of the transcription factor NF-kappa B by inflammatory cytokines involves the successive action of NF-kappa B-inducing kinase (NIK) and two Ikappa B kinases, IKK-alpha and IKK-beta . Here we show that NIK preferentially phosphorylates IKK-alpha over IKK-beta , leading to the activation of IKK-alpha kinase activity. This phosphorylation of IKK-alpha occurs specifically on Ser-176 in the activation loop between

Lei Ling; Zhaodan Cao; David V. Goeddel

1998-01-01

96

UV-B induced free radical production in plant leaves and isolated thylakoid membranes  

Microsoft Academic Search

Illumination of isolated thylakoid membranes by UV-B light does not result in singlet oxygen production but induces free radicats, mainly hydroxyl and carbon-centered (methyl-like) ones. The absence of singlet oxygen demonstrates that the primary site of UV-B induced electron transport impariment in photosystem II is different from that of photoinhibition by excess photosynthetically active radiation. Membrane preparations from UV-B pre-illuminated

Éva Hideg; Imre Vass

1996-01-01

97

Spaceflight Associated Apoptosis  

NASA Technical Reports Server (NTRS)

Lymphoid tissues have been shown to atrophy in rats flown on Russian spaceflights. Histological examination indicated evidence for cell degradation. Lymphoid tissues from rats flown on Spacelab Life Sciences-2 mission were analyzed for apoptosis by evidence of fragmented lymphocytes, which could be engulfed by macrophages, or DNA strand breaks using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Apoptosis was not detected in the thymus and spleen collected inflight or from the synchronous ground rats but was detected in the thymus, spleen and inguinal lymph node of the flight animals on recovery. These results indicate that the apoptosis observed in the lymphatic tissues of the rats on recovery could have been induced by the gravitational stress of reentry, corroborating the findings from the early space-flight observations.

Ichiki, Albert T.; Gibson, Linda A.; Allebban, Zuhair

1996-01-01

98

Retention behaviour of some high-intensity sweeteners on different SPE sorbents.  

PubMed

The objective of this paper is to provide information about application of solid-phase extraction (SPE) for isolation of nine high-intensity sweeteners (acesulfame-K, alitame, aspartame, cyclamate, dulcin, neotame, saccharin, sucralose and neohesperidin dihydrochalcone) from aqueous solutions. The influence of several types of LC-MS compatible buffers (different pH values and compositions) on their recovery has been studied and discussed. A number of commercially available SPE cartridges, such as Chromabond C18ec, Strata-X RP, Bakerbond Octadecyl, Bakerbond SDB-1, Bakerbond SPE Phenyl, Oasis HLB, LiChrolut RP-18, Supelclean LC-18, Discovery DSC-18 and Zorbax C18 were tested in order to evaluate their applicability for the isolation of analytes. Very high recoveries (better than 92%) of all studied compounds were obtained using formic acid-N,N-diisopropylethylamine buffer adjusted to pH 4.5 and C(18)-bonded silica sorbents. Behaviour of polymeric sorbents strongly depends on their structure. Strata-X RP behaves much like a C(18)-bonded silica sorbent. Recoveries obtained using Oasis HLB were comparable with those observed for silica-based sorbents. The only compound less efficiently (83%) retained by this sorbent was cyclamate. Bakerbond SDB-1 shows unusual selectivity towards aspartame and alitame. Recoveries of these two sweeteners were very low (26 and 42%, respectively). It was also found that aspartame and alitame can be selectively separated from the mixture of sweeteners using formic acid-triethylamine buffer at pH 3.5. PMID:20875571

Zygler, Agata; Wasik, Andrzej; Namie?nik, Jacek

2010-10-15

99

Regulation of Apoptosis by Caspases.  

National Technical Information Service (NTIS)

Apoptosis is a cellular suicide mechanism critical for removing cells that may be harmful or no longer needed. Abnormal apoptosis may result in cancer and neural degenerative diseases such as Alzheimer's disease. Caspases are a family of cysteine protease...

J. Yuan

2001-01-01

100

Regulation of Apoptosis by Caspases.  

National Technical Information Service (NTIS)

Caspases are a family of cysteine proteases that play important roles in regulating apoptosis, a genetically encoded cellular suicide mechanism. To determine the mechanism by which caspases regulate apoptosis. We carried out a screen to identify substrate...

J. Yuan

1999-01-01

101

Molecularly imprinted silica as a selective SPE sorbent for triazine herbicides.  

PubMed

A molecularly imprinted organically modified silica was prepared through a simple sol-gel procedure and evaluated as a specific sorbent for SPE of triazine herbicides. The material proved to be highly selective for the template molecule, atrazine, as well as for other structurally related species such as simazine and propazine. The performance of this material was shown to be comparable with commercial acrylate-based molecularly imprinted polymers. The molecularly imprinted silica was applied for the determination of trace levels of the target triazine analytes in sugar cane juice (locally called "garapa"). PMID:20201047

Gomes Costa Silva, Raquel; Rosa Morais Vigna, Camila; Bottoli, Carla B G; Collins, Carol H; Augusto, Fabio

2010-05-01

102

LC-MS-MS determination of brostallicin in human plasma following automated on-line SPE.  

PubMed

LC-MS-MS method using automated on-line solid-phase extraction (SPE) has been developed and validated for the quantitation of brostallicin (I), a new distamycin derivative, in human plasma. I is a DNA minor groove binder currently under phase I-II clinical evaluation as an anticancer drug. Plasma (0.4 ml) was spiked with 0.2 ml stable label IS solution and placed in a 96-well plate maintained at +4 degrees C. Aliquots of 0.1 ml of prepared samples were loaded into the on-line SPE HySphere Resin SH cartridges (10 mm x 2 mm ID) and the analytes back eluted with the mobile phase into LC-MS-MS system. A Platinum Cyano column (100 mm x 4.6 mm, 3.6 microm) was used to perform the chromatographic analysis. The mobile phase was acetonitrile-ammonium formate buffer (pH 3.5; 20 mM) (70:30, v/v) at a flow rate of 1.0 ml/min. LC flow was split so that 300 microl/min was directed toward the mass spectrometer interface. Retention time of I was 2.6 min and the total cycle time was 8 min. MS detection used an Applied Biosystems/MDS SCIEX API 365 with a TurboIonSpray interface and MRM (m/Z: 725/257 for I and m/Z: 729/257 for IS) operated in positive ion mode. The method was validated over the calibration range 0.124-497 ng/ml. A negligible carry-over effect from the system was observed. In spite of the known instability of I in human plasma (about 20% decrease over 12 h), the ratio analyte/IS peak area showed good stability over the analysis time required for 96 samples. The automated on-line SPE method can be considered as a valid alternative to the off-line manual SPE procedure previously developed. PMID:12899950

Calderoli, Sara; Colombo, Emiliana; Frigerio, Enrico; James, Christopher A; Sibum, Martin

2003-08-01

103

Estimates of HZE particle contributions to SPE radiation exposures on interplanetary missions  

NASA Technical Reports Server (NTRS)

Estimates of radiation doses resulting from possible HZE (high energy heavy ion) components of Solar Particle Events (SPEs) are presented for crews of manned interplanetary missions. The calculations assume a model spectrum obtained by folding measured solar flare HZE particle abundances with the measured energy spectra of SPE alpha particles. These hypothetical spectra are then transported through aluminum spacecraft shielding. The results, presented as estimates of absorbed dose and dose equivalent, indicate that HZE components by themselves are not a major concern for crew protection but should be included in any overall risk assessment. The predictions are found to be sensitive to the assumed spectral hardness parameters.

Townsend, L. W.; Cucinotta, F. A.; Wilson, J. W.; Bagga, R.

1994-01-01

104

Connective tissue growth factor mediates transforming growth factor b-induced collagen synthesis: down- regulation by cAMP  

Microsoft Academic Search

Connective tissue growth factor (CTGF) is a cysteine-rich peptide synthesized and secreted by fibroblastic cells after activation with transforming growth factor beta (TGF-b) that acts as a downstream mediator of TGF-b-induced fibroblast proliferation. We performed in vitro and in vivo studies to determine whether CTGF is also essential for TGF-b-induced fibroblast collagen synthesis. In vitro studies with normal rat kidney

MATTHEW R. DUNCAN; KEN S. FRAZIER; SUSAN ABRAMSON; SHAWN WILLIAMS; HELENE KLAPPER; XINFAN HUANG; GARY R. GROTENDORST

105

Geologic Assessment of the Damage Zone from the Second Test at Source Physics Experiment-Nevada (SPE-N)  

SciTech Connect

The National Center for Nuclear Security, established by the U.S. Department of Energy, National Nuclear Security Administration (NNSA), is conducting a series of explosive tests at the Nevada National Security Site that are designed to increase the understanding of certain basic physical phenomena associated with underground explosions. These tests will aid in developing technologies that might be used to detect underground nuclear explosions in support of verification activities for the Comprehensive Nuclear-Test-Ban Treaty. The initial project is a series of explosive tests, known collectively as the Source Physics Experiment-Nevada (SPE-N), being conducted in granitic rocks. The SPE-N test series is designed to study the generation and propagation of seismic waves. The results will help advance the seismic monitoring capability of the United States by improving the predictive capability of physics-based modeling of explosive phenomena. The first SPE N (SPE-N-1) test was conducted in May 2011, using 100 kg of explosives at the depth of 54.9 m in the U 15n source hole. SPE-N-2 was conducted in October 2011, using 1,000 kg of explosives at the depth of 45.7 m in the same source hole. The SPE-N-3 test was conducted in the same source hole in July 2012, using the same amount and type of explosive as for SPE-N-2, and at the same depth as SPE-N-2, within the damage zone created by the SPE-N-2 explosion to investigate damage effects on seismic wave propagation. Following the SPE-N-2 shot and prior to the SPE-N-3 shot, the core hole U-15n#10 was drilled at an angle from the surface to intercept the SPE-N-2 shot point location to obtain information necessary to characterize the damage zone. The objective was to determine the position of the damage zone near the shot point, at least on the northeast, where the core hole penetrated it, and obtain information on the properties of the damaged medium. Geologic characterization of the post-SPE-N-2 core hole included geophysical logging, a directional survey, and geologic description of the core to document visual evidence of damage. Selected core samples were provided to Sandia National Laboratories (SNL) for measurement of physical and mechanical properties. A video was also run in the source hole after it was cleaned out. A significant natural fault zone was encountered in the angle core hole between 5.7 and 7.5 m from the shot point. However, several of the fractures observed in the core hole are interpreted as having been caused by the explosion. The fractures are characterized by a “fresh,” mechanically broken look, with uncoated and very irregular surfaces. They tend to terminate against natural fractures and have orientations that differ from the previously defined natural fracture sets; they are common starting at about 5.4 m from the shot point. Within about 3.3 m of the shot point to the end of the recovered core at 1.6 m from the shot point, some of the core samples are softer and lighter in color, but do not appear to be weathered. It is thought this could be indicative of the presence of distributed microfracturing.

Townsend, M. J.; Huckins-Gang, H. E.; Prothro, L. B.; Reed, D. N.

2012-12-01

106

iBioSeminar: Apoptosis  

NSDL National Science Digital Library

Apoptosis is a form of programmed cell death that plays important roles during animal development, immune response, elimination of damaged cells, and maintenance of tissue homeostasis. Apoptosis is executed by intracellular proteases named caspases that are activated during the onset of apoptosis by extrinsic and intrinsic pathways.

Xiaodong Wang (Howard Hughes Medical Institute and UT-Southwestern Medical Center;Dept of Biochemistry)

2011-06-08

107

Apoptosis in Colorectal Cancer  

PubMed Central

Abstract Apoptosis is an inborn process that has been preserved during evolution; it allows the cells to systematically inactivate, destroy and dispose of their own components thus leading to their death. This programme can be activated by both intra and extracellular mechanisms. The intracellular components involve a genetically defined development programme while the extracellular aspects regard endogenous proteins, cytokines and hormones as well as xenobiotics, radiations, oxidative stress and hypoxia. The ability of a cell to enter apoptosis as a response to a “death" signal depends on its proliferative status, the position in the cell cycle and also on the controlled expression of those genes that have the capacity of promoting and inhibiting cell death. The fine regulation of these parameters needs to be maintained in order to ensure the physiological environment required for the induction of apoptosis. Any malfunction in any of the steps of controlled cellular death can lead to dysfunctions and, as a consequence, to different pathological conditions. The importance of apoptosis lies in its active nature and in the potential of controlling biological systems.

Stoian, M; State, N; Stoica, V; Radulian, G

2014-01-01

108

Senescence Apoptosis methyltransferase  

E-print Network

Oncogenic stress ARF MDM2 p53 Senescence Apoptosis DNA methyltransferase inhibitors to reactivate by the MDM2 protein. Various cellular stresses, including DNA damage, can activate p53, and once triggered, p in tumours that overexpress MDM2 by using MDM2 inhibitors such as the nutlin molecules12

Utrecht, Universiteit

109

Simple SPE-GC method for anethole determination in human serum.  

PubMed

Recently, much attention has been given to congener analysis, which can be used to check the possibility of postoffence drinking claims in forensic toxicology. In this type of analysis, the information given by the defendant regarding the type, quantity, and time of consumption of a specific alcoholic beverage is used to calculate theoretically expected congener concentration in the blood and this is compared with the analytically determined concentrations in the blood sample. Many alcoholic drinks aromatized with essential oils of plants and fruits contain a specific congener, for example, anethole in aniseed drinks. The present study describes the GC procedure of anethole analysis in human plasma using SPE as the sample preparation method. The procedure involves the protein precipitation process, which generally degrades the protein-analyte complex, and SPE isolation of anethole from the examined materials. This analytical approach is proposed as a method of choice for the estimation of anethole concentration in human fluids after the consumption of alcoholic beverages and other foods containing the substance. The described method is characterized by a low LOD (8.33 ng/g) and a very high recovery (average recovery 98.37%) of the analyte. PMID:24302657

Dawidowicz, Andrzej L; Dybowski, Michal P

2014-02-01

110

The enteropathogenic Escherichia coli effector NleH inhibits apoptosis induced by Clostridium difficile toxin B  

PubMed Central

Clostridium difficile is a leading cause of nosocomial infections, causing a spectrum of diseases ranging from diarrhoea to pseudomembranous colitis triggered by a range of virulence factors including C. difficile toxins A (TcdA) and B (TcdB). TcdA and TcdB are monoglucosyltransferases that irreversibly glycosylate small Rho GTPases, inhibiting their ability to interact with their effectors, guanine nucleotide exchange factors, and membrane partners, leading to disruption of downstream signalling pathways and cell death. In addition, TcdB targets the mitochondria, inducing the intrinsic apoptotic pathway resulting in TcdB-mediated apoptosis. Modulation of apoptosis is a common strategy used by infectious agents. Recently, we have shown that the enteropathogenic Escherichia coli (EPEC) type III secretion system effector NleH has a broad-range anti-apoptotic activity. In this study we examined the effects of NleH on cells challenged with TcdB. During infection with wild-type EPEC, NleH inhibited TcdB-induced apoptosis at both low and high toxin concentrations. Transfected nleH1 alone was sufficient to block TcdB-induced cell rounding, nuclear condensation, mitochondrial swelling and lysis, and activation of caspase-3. These results show that NleH acts via a global anti-apoptotic pathway. PMID:20223805

Robinson, Keith S.; Mousnier, Aurelie; Hemrajani, Cordula; Fairweather, Neil; Berger, Cedric N.; Frankel, Gad

2010-01-01

111

Mitochondrial alterations in apoptosis.  

PubMed

Besides their conventional role as energy suppliers for the cell, mitochondria in vertebrates are active regulators of apoptosis. They release apoptotic factors from the intermembrane space into the cytosol through a mechanism that involves the Bcl-2 protein family, mediating permeabilization of the outer mitochondrial membrane. Associated with this event, a number of additional changes affect mitochondria during apoptosis. They include loss of important mitochondrial functions, such as the ability to maintain calcium homeostasis and to generate ATP, as well as mitochondrial fragmentation and cristae remodeling. Moreover, the lipidic component of mitochondrial membranes undergoes important alterations in composition and distribution, which have turned out to be relevant regulatory events for the proteins involved in apoptotic mitochondrial damage. PMID:24732580

Cosentino, Katia; García-Sáez, Ana J

2014-07-01

112

Observing Silicate-Rich Asteroids in Technicolor: Detailed Compositional Constraints from SpeX.  

NASA Astrophysics Data System (ADS)

We have recently begun a new survey of sili-cate-rich asteroids using SpeX, a low- to medium-resolution infrared spectrograph, at the Infrared Telescope Facility (IRTF) on Mauna Kea, Hawaii [1]. In its low-resolution mode (R approx.100), SpeX can produce spectra of faint asteroids from 0.8 to 2.5 microns with S/N comparable to data typically collected with visible wavelength CCDs. The SpeX data have been combined with visible CCD data measured during the SMASSII survey [2] to produce high S/N (often greater than100) spectra from 0.44 to 2.5 microns for several asteroids. This rich dataset includes subtle spectral signatures that we have analyzed with the Modified Gaussian absorption band model [3]. Among our results are clear unambiguous evidence for the presense of both high- and low-calcium pyroxene (HCP and LCP) as well as olivine and plagioclase. The quality of these data allow us to use the proportion of HCP relative to LCP, to constrain the petrologic history of these bodies. Very primitive bodies (e.g. primitive achondrites) have less than 10 percent HCP, while moderately evolved bodies (e.g. ordinary chondrites) have 15-20 percent HCP, and highly evolved bodies (e.g. basaltic achondrites) have more than 25 percent of their pyroxene as HCP. Our current dataset contains several asteroids, including members of the Merxia and Agnia families, with spectra that show little to no evidence for olivine, but instead are dominated by pyroxene absorptions and include significant (more than 40 percent) proportions of HCP. This HCP content implies a history of partial melting and silicate differentiation. As such we are actively examining smaller members of the Agnia and Merxia families to futher constrain the petrologic history of these bodies. References: [1] Rayner, J. T. et al. (1998) Proc. SPIE, 3354, 468-479. [2] Bus, S. J. et al. (2002) Icarus, 158, 106-145. [3] Sunshine, J. M. et al. (1990) JGR, 95, 6955-6966.

Sunshine, J. M.; Bus, S. J.; Burbine, T. H.; McCoy, T. J.; Binzel, R. P.

2002-12-01

113

Mitochondria and Apoptosis  

NSDL National Science Digital Library

A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins. The different signals that converge on mitochondria to trigger or inhibit these events and their downstream effects delineate several major pathways in physiological cell death.

Douglas Green (La Jolla Institute for Allergy and Immunology;); John Reed (Burnham Institute;)

1998-08-28

114

Targeting apoptosis in autoimmune hepatitis.  

PubMed

Apoptosis is the predominant mechanism of liver cell death in autoimmune hepatitis, and interventions that can modulate this activity are emerging. The aim of this review was to describe the apoptotic mechanisms, possible aberrations, and opportunities for intervention in autoimmune hepatitis. Studies cited in PubMed from 1972 to 2014 for autoimmune hepatitis, apoptosis in liver disease, apoptosis mechanisms, and apoptosis treatment were examined. Apoptosis is overactive in autoimmune hepatitis, and the principal pathway of cell death is receptor mediated. Surface death receptors are activated by extrinsic factors including liver-infiltrating cytotoxic T cells and the cytokine milieu. The executioner caspases 3 and 7 cleave nuclear deoxyribonucleic acid, and the release of apoptotic bodies can stimulate inflammatory, immune, and fibrotic responses. Changes in mitochondrial membrane permeability can be initiated by caspase 8, and an intrinsic pathway of apoptosis can complement the extrinsic pathway. Defects in the apoptosis of activated effector cells can prolong their survival and sustain the immune response. Caspase inhibitors have been used in diverse experimental and human diseases to retard apoptosis. Oligonucleotides that inhibit the signaling of toll-like receptors can limit the presentation of auto-antigens, and inhibitors of apoptosis that extend the survival of effector cells can be blocked by antisense oligonucleotides. Mechanisms that enhance the clearance of apoptotic bodies and affect key signaling pathways are also feasible. Interventions that influence the survival of liver and effector cells by altering their apoptosis are candidates for study in autoimmune hepatitis. PMID:25038736

Czaja, Albert J

2014-12-01

115

Copyright 2006, Society of Petroleum Engineers This paper was prepared for presentation at the 2006 SPE Eastern Regional Meeting held in  

E-print Network

SPE Eastern Regional Meeting held in Canton, Ohio, U.S.A., 11­13 October 2006. This paper was selected Librarian, SPE, P.O. Box 833836, Richardson, TX 75083-3836 U.S.A., fax 01-972-952-9435. Abstract Recent the recovery from mature reservoirs. Identifying sweet spots in these fields for in-fill drilling and ranking

Mohaghegh, Shahab

116

Top-Down Modeling; Practical, Fast-Track, Reservoir Modeling for Shale Formations AAPG/SEG/SPE/SPWLA Hedberg Conference, Austin, TX December 2010  

E-print Network

development strategy and recovery enhancement. Top-Down Modeling is an elegant integration of state-of-the1 Top-Down Modeling; Practical, Fast-Track, Reservoir Modeling for Shale Formations AAPG/SEG/SPE/SPWLA Hedberg Conference, Austin, TX December 2010 AAPG/SEG/SPE/SPWLA HEDBERG CONFERENCE "CRITICAL ASSESSMENT

Mohaghegh, Shahab

117

Application of graphene for the SPE clean-up of organophosphorus pesticides residues from apple juices.  

PubMed

In this paper, an effective graphene-based SPE clean-up procedure coupled with GC-MS was developed for the determination of organophosphorus pesticide residues in apple juices. The apple juice samples were diluted with water and could be loaded onto the cartridge directly. Several parameters affecting the extraction efficiency were investigated, including the type of elution, washing solution, and sample pH. Under the optimized conditions, excellent limits of quantitation for the target analytes were found to be 0.15-1.18 ng/mL, and the average recoveries of the analytes at two spiked levels for real-sample analysis ranged from 69.8 to 106.2% with RSDs less than 7.3%. Furthermore, the graphene-based cartridges exhibited superior reusability for juice sample analysis. The proposed method is sensitive, simple, and cost saving, and provides a detection platform for the monitoring of pesticide residues. PMID:24307600

Han, Qiang; Wang, Zonghua; Xia, Jianfei; Zhang, Xiaoqiong; Wang, Hongwu; Ding, Mingyu

2014-01-01

118

Determination of gadolinium in river water by SPE preconcentration and ICP-MS.  

PubMed

An analytical scheme was developed for the determination of Gd-diethylenetriaminepentaacetate (Gd-DTPA), Gd and the other rare earth elements (REE) in river water by inductively coupled plasma (quadrupole) mass spectrometry (ICP-Q-MS). The preconcentration step was essential, since the limits of detection of this multielemental analytical technique are higher than the trace concentrations of the interesting elements in river water. Solid phase extraction (SPE) with different commercially available complexing agents (Chelex 100, Toyopearl and ethylhexylphosphates) was employed for the preconcentration of REE. The investigations revealed that complex stability (varying in dependence of the pH value) has a strong influence on the degree of the enrichment of Gd-DTPA. Based on acidified water samples (pH<3) a procedure using ethylhexylphosphates was proposed for the preconcentration of Gd and REE from surface water samples. For this purpose C(18)-cartridges loaded with ethylhexylphosphates were used, resulting in an enrichment factor of 40. PMID:18969433

Hennebrüder, Kristina; Wennrich, Rainer; Mattusch, Jürgen; Stärk, Hans-Joachim; Engewald, Werner

2004-05-28

119

Optimization of an SPE and GC/MS Method for Analyzing Endocrine Disrupting Compounds in Water  

NASA Astrophysics Data System (ADS)

Endocrine disrupting compounds (EDCs) are compounds that interrupt hormonal functions in the body. The literature reports the presence of EDCs in all environmental matrices (air, water and soil) at concentrations of at least 1 nanogram/liter (ng/l), which may be high enough to induce adverse health effects. Therefore, reliable analytical methods for detecting trace amounts of EDCs in water is very important for investigating and controlling their concentrations in the environment. This study investigated a method for analyzing four known or suspected EDCs (chlorpyrifos, musk HHCB, diethyl phthalate, and butylated hydroxyanisole) in water samples. The analytical method was based on the USGS wastewater method developed by Zaugg et al. (2001), but modified, using solid phase extraction (SPE) followed by gas chromatography and mass spectrometry (GC/MS) analysis. The EDCs were extracted using 60mg Water Oasis hydrophilic-lipophillic balance (HLB) extraction cartridges. The SPE efficiency was investigated by using different initial extraction volumes and different EDC concentrations. The lowest concentration was 1ng/l and the lowest extraction volume was 100mL. Results of the study indicate that the initial oven temperature conditions and rate of temperature increases affects the peak signal to noise ratio and the sample run-time in the GC/MS. An increase in gas flow rate did not show any significant changes and hence was maintained at 1ml/min. Preliminary data suggests that the percent recovery of the compounds obtained using this method either met or exceeded those presented by Zaugg et al. (2001) as the USGS wastewater method.

Thomas, S. M.; Bodour, A.; Murray, K. E.

2006-12-01

120

NF-?B inducing kinase: a key regulator in the immune system and in cancer  

PubMed Central

NF-?B inducing kinase (NIK) is a kinase that activates the canonical and non-canonical NF-?B pathways to control transcriptional expression of certain proteins such as cytokines, chemokines and NF-?B signaling molecules. Many advances have been made in understanding the molecular mechanisms by which the stability of NIK is regulated to affect downstream signaling. Genetic mouse models suggest that NIK has an essential role in regulation of the immune system as well as in the bone microenvironment. Increasing evidence links NIK to the tumorigenesis of hematological cancers, such as multiple myeloma, and solid tumors, such as pancreatic carcinoma and melanoma. Understanding the mechanism by which NIK is de-regulated will potentially provide therapeutic options for certain diseases such as autoimmunity and cancer. PMID:20685151

Thu, Yee Mon; Richmond, Ann

2010-01-01

121

Recombinant Clostridium difficile toxin B induces endoplasmic reticulum stress in mouse colonal carcinoma cells.  

PubMed

Clostridium difficile is the main cause of antibiotic-associated diarrhea and pseudomembranous colitis in humans and animals. Its pathogenicity is primarily linked to the secretion of two exotoxins (TcdA and TcdB). Although great progress in the toxic mechanism of TcdA and TcdB has been achieved, there are many conflicting reports about the apoptotic mechanism. More importantly, apoptotic endoplasmic reticulum (ER) stress has been reported in cells treated with Shiga toxins-another kind of cytotoxins that can cause diarrhea and colitis. Herein we checked whether TcdB can induce ER stress. The results showed that recombinant TcdB (rTcdB) activated molecular markers of unfolded protein response, suggesting that rTcdB induced ER stress in CT26 cells. However, rTcdB did not induce the up-regulation of C/EBP homologous protein (CHOP), a classic mediator of apoptotic ER stress, but it activated the precursor of cysteine aspartic acid-specific protease 12 (caspase-12), a controversial mediator of apoptotic ER stress. Besides, glucosyltransferase activity-deficient mutant recombinant TcdB induced ER stress, though it has no cytotoxic or cytopathic effect on CT26 cells. Altogether, these data demonstrated that ER stress induced by rTcdB is glucosyltransferase-independent, indicating that ER stress induced by rTcdB is non-apoptotic. This work also offers us a new insight into the molecular mechanism of CHOP protein expression regulation and the role of CHOP expression in ER stress. PMID:25274332

Sun, Chunli; Wang, Haiying; Chen, Shuyi; Li, Zhendong; Li, Shan; Wang, Jufang

2014-11-01

122

Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells.  

PubMed

Natural products are a great source of cancer chemotherapeutic agents. The present study was conducted to investigate whether cucurbitacin B (CuB), one of the most potent and widely used cucurbitacins, inhibits proliferation and induces apoptosis in the A549 lung cancer cell line. Furthermore, CuB induced apoptosis of A549 cells in a -concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. The present study also demonstrated that CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition. CuB may prove to be a useful approach for the chemotherapy of lung cancer. PMID:25242136

Zhang, Meng; Bian, Zhi-Gang; Zhang, Yi; Wang, Jia-He; Kan, Liang; Wang, Xin; Niu, Hui-Yan; He, Ping

2014-12-01

123

Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells  

PubMed Central

Natural products are a great source of cancer chemotherapeutic agents. The present study was conducted to investigate whether cucurbitacin B (CuB), one of the most potent and widely used cucurbitacins, inhibits proliferation and induces apoptosis in the A549 lung cancer cell line. Furthermore, CuB induced apoptosis of A549 cells in a concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. The present study also demonstrated that CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition. CuB may prove to be a useful approach for the chemotherapy of lung cancer. PMID:25242136

ZHANG, MENG; BIAN, ZHI-GANG; ZHANG, YI; WANG, JIA-HE; KAN, LIANG; WANG, XIN; NIU, HUI-YAN; HE, PING

2014-01-01

124

Copyright 2006, Society of Petroleum Engineers This paper was prepared for presentation at the 2006 SPE Annual Technical Conference and  

E-print Network

of where and by whom the paper was presented. Write Librarian, SPE, P.O. Box 833836, Richardson, TX 75083 application of a new compositional code for the numerical simulation of oil-base mud invasion and formation of simulation results against those obtained with a commercial code confirms the efficiency, accuracy

Torres-Verdín, Carlos

125

Copyright 2006, Society of Petroleum Engineers This paper was prepared for presentation at the 2006 SPE Annual Technical Conference and  

E-print Network

of where and by whom the paper was presented. Write Librarian, SPE, P.O. Box 833836, Richardson, TX 75083 the mechanically stressed rock formations are probed with a dual-packer formation tester to assess petrophysical pressure probes. The processes of multi-phase flow in the near-wellbore region due to mud-filtrate invasion

Torres-Verdín, Carlos

126

Near-Infrared Spectral Monitoring of Triton with IRTF/SpeX II: Spatial Distribution and Evolution of Ices  

E-print Network

's near-infrared spectrum for nine yeaNear-Infrared Spectral Monitoring of Triton with IRTF/SpeX II: Spatial Distribution and Evolution. 1999; Hicks and Buratti 2004), as well as longer term evolution at near-infrared wavelengths (reviewed

Young, Leslie A.

127

HybridSPE: A novel technique to reduce phospholipid-based matrix effect in LC-ESI-MS Bioanalysis  

PubMed Central

When complex biological materials are analyzed without an adequate sample preparation technique, MS signal and response undergo significant alteration and result in poor quantification and assay. This problem generally takes place due to the presence of several endogenous materials component in samples. One of the major causes of ion suppression in bioanalysis is the presence of phospholipids during LC-MS analysis. The phospholipid-based matrix effect was investigated with a commercially available electro spray ionization (ESI) source coupled with a triple quadrupole mass spectrometer. HybridSPE dramatically reduced the levels of residual phospholipids in biological samples, leading to significant reduction in matrix effects. This new procedure that combines the simplicity of precipitation with the selectivity of SPE allows obtaining much cleaner extracts than with conventional procedures. HybridSPE-precipitation procedure provides significant improvement in bioanalysis and a practical and fast way to ensure the avoidance of phospholipids-based matrix effects. The present review outlines the HybridSPE technique to minimize phospholipids-based matrix effects on LC–ESI-MS bioanalysis. PMID:23248558

Ahmad, Shafeeque; Kalra, Harsh; Gupta, Amit; Raut, Bharat; Hussain, Arshad; Rahman, Md. Akhlaquer

2012-01-01

128

Copyright 2004, Society of Petroleum Engineers Inc. This paper was prepared for presentation at the SPE Annual Technical Conference and  

E-print Network

the paper was presented. Write Librarian, SPE, P.O. Box 833836, Richardson, TX 75083-3836, U.S.A., fax 01-972-952-9435. ABSTRACT This paper presents a new and novel technique for determining the in-situ stress profile. It is well established, that in-situ stress cannot be generated from well logs alone. This is because two

Mohaghegh, Shahab

129

We present a new microphone array calibration algorithm spe-cifically designed for speech recognition. Currently, micro-  

E-print Network

Abstract We present a new microphone array calibration algorithm spe- cifically designed for speech and actual microphone array data. 1. Introduction State-of-the-art speech recognition systems are known allevi- ated by the use of multiple microphones to capture the speech signal. Microphone arrays record

Stern, Richard

130

Ribosome Inactivating Proteins and Apoptosis  

Microsoft Academic Search

\\u000a Ribosome inactivating proteins (RIPs) are RNA N-glycosidases which potently inhibit translation by inactivating ribosomes. RIPs have also been shown to possess the ability\\u000a to induce apoptosis. A number of RIPs from different sources have been used to study the mechanism of apoptosis induction.\\u000a However, it is being observed that these toxins trigger apoptosis in different cell types via different mechanisms;

Deepa Sikriwal; Janendra K. Batra

131

Apoptosis Resistance in Endometriosis  

PubMed Central

Introduction In a cytological analysis of endometriotic lesions neither granulocytes nor cytotoxic T-cells appear in an appreciable number. Based on this observation we aimed to know, whether programmed cell death plays an essential role in the destruction of dystopic endometrium. Disturbances of the physiological mechanisms of apoptosis, a persistence of endometrial tissue could explain the disease. Another aspect of this consideration is the proliferation competence of the dystopic mucous membrane. Methods Endometriotic lesions of 15 patients were examined through a combined measurement of apoptosis activity with the TUNEL technique (terminal deoxyribosyltransferase mediated dUTP Nick End Labeling) and the proliferation activity (with the help of the Ki-67-Antigens using the monoclonal antibody Ki-S5). Results Twelve out of 15 women studied showed a positive apoptotic activity of 3-47% with a proliferation activity of 2-25% of epithelial cells. Therefore we concluded that the persistence of dystopic endometrium requires proliferative epithelial cells from middle to lower endometrial layers. Conclusion A dystopia misalignment of the epithelia of the upper layers of the functionalism can be rapidly eliminated by apoptotic procedures. PMID:23678417

Salmassi, Ali; Acar-Perk, Bengi; Schmutzler, Andreas G.; Koch, Kerstin; Pungel, Frank; Jonat, Walter; Mettler, Liselotte

2011-01-01

132

Mitochondrial Redox Signaling during Apoptosis  

Microsoft Academic Search

The regulatory role of cellular redox state during apoptosis is still controversial. Early redoxsignaling can transduce divergent upstream signals to mitochondria and initiate apoptosis. Onthe other hand, release of mitochondrial cytochrome c triggers generation of reactive oxygenspecies (ROS) and renders apoptotic cells much more oxidized. Although the sequential caspaseactivation does not have apparent redox-sensitive components, redox signaling provides aseparate pathway

Jiyang Cai; Dean P. Jones

1999-01-01

133

The Development and Optimization of Techniques for Monitoring Water Quality on-Board Spacecraft Using Colorimetric Solid-Phase Extraction (C-SPE)  

SciTech Connect

The main focus of this dissertation is the design, development, and ground and microgravity validation of methods for monitoring drinking water quality on-board NASA spacecraft using clorimetric-solid phase extraction (C-SPE). The Introduction will overview the need for in-flight water quality analysis and will detail some of the challenges associated with operations in the absence of gravity. The ability of C-SPE methods to meet these challenges will then be discussed, followed by a literature review on existing applications of C-SPE and similar techniques. Finally, a brief discussion of diffuse reflectance spectroscopy theory, which provides a means for analyte identification and quantification in C-SPE analyses, is presented. Following the Introduction, four research chapters are presented as separate manuscripts. Chapter 1 reports the results from microgravity testing of existing C-SPE methods and procedures aboard NASA's C-9 microgravity simulator. Chapter 2 discusses the development of a C-SPE method for determining the total concentration of biocidal silver (i.e., in both dissolved and colloidal forms) in water samples. Chapter 3 presents the first application of the C-SPE technique to the determination of an organic analyte (i.e., formaldehyde). Chapter 4, which is a departure from the main focus of the thesis, details the results of an investigation into the effect of substrate rotation on the kinetics involved in the antigen and labeling steps in sandwich immunoassays. These research chapters are followed by general conclusions and a prospectus section.

April Hill

2007-12-01

134

Cholesterol oxidase from Bordetella species promotes irreversible cell apoptosis in lung adenocarcinoma by cholesterol oxidation.  

PubMed

Cholesterol oxidase (COD), an enzyme catalyzing the oxidation of cholesterol, has been applied to track the distribution of membrane cholesterol. Little investigations about the effect of COD on tumor cells have been performed. In the present study, we provided evidence that COD from Bordetella species (COD-B), induced apoptosis of lung cancer cells in vitro and in vivo. COD-B treatment inhibited Akt and ERK1/2 phosphorylation in dose- and time-dependent manner, which was not reversed and was even aggravated by cholesterol addition. Further investigation indicated that COD-B treatment promoted the generation of reactive oxygen species (ROS) and that cholesterol addition further elevated ROS levels. Moreover, COD-B treatment resulted in JNK and p38 phosphorylation, downregulation of Bcl-2, upregulation of Bax, activated caspase-3 and cytochrome C release, which likely responded to freshly produced hydrogen peroxide that accompanied cholesterol oxidation. Catalase pretreatment could only partially prevent COD-B-induced events, suggesting that catalase inhibited H2O2-induced signal transduction but had little effect on signal pathways involved in cholesterol depletion. Our results demonstrated that COD-B led to irreversible cell apoptosis by decreasing cholesterol content and increasing ROS level. In addition, COD-B may be a promising candidate for a novel anti-tumor therapy. PMID:25118932

Liu, J; Xian, G; Li, M; Zhang, Y; Yang, M; Yu, Y; Lv, H; Xuan, S; Lin, Y; Gao, L

2014-01-01

135

Ram ion scattering caused by Space Shuttle v x B induced differential charging  

NASA Technical Reports Server (NTRS)

Observations of secondary, high-inclination ions streams have been reported in the literature. The authors of these previous papers attributed the source of the secondary ions to a disturbed region in the plasma about 10 m from the Space Shuttle Orbiter. A new theory has been developed which shows how v x B induced differential charging on the plasma diagnostics package (PDP) can scatter the ram ion flux. Some of these ions are reflected back to the PDP and may be the sorce of the observed ion distributions. The effect is unique to large spacecraft; it occurs only when the magnitude of the induced v x B potentials are much larger than the electron thermal energy and of the order of the ion ram energy. That the ion streams observed at large angles must have been reflected from the PDP surface is demonstrated with three-dimensional sheath and particle trajectory calculations using the low earth orbit version of the NASA Charging Analyzer Program (NASCAP/LEO).

Katz, I.; Davis, V. A.

1987-01-01

136

Role of WNT7B-induced Noncanonical Pathway in Advanced Prostate Cancer  

PubMed Central

Advanced prostate cancer is characterized by incurable castration-resistant progression and osteoblastic bone metastasis. While androgen deprivation therapy remains the primary treatment for advanced prostate cancer, resistance inevitably develops. Importantly, mounting evidence indicates that androgen receptor (AR) signaling continues to play a critical role in the growth of advanced prostate cancer despite androgen deprivation. While the mechanisms of aberrant AR activation in advanced prostate cancer have been extensively studied, the downstream AR target genes involved in the progression of castration resistance are largely unknown. Here, we identify WNT7B as a direct AR target gene highly expressed in castration-resistant prostate cancer (CRPC) cells. Our results show that expression of WNT7B is necessary for the growth of prostate cancer cells and that this effect is enhanced under androgen-deprived conditions. Further analyses reveal that WNT7B promotes androgen-independent growth of CRPC cells likely through the activation of protein kinase C isozymes. Our results also show that prostate cancer-produced WNT7B induces osteoblast differentiation in vitro through a direct cell–cell interaction, and that WNT7B is upregulated in human prostate cancer xenografts that cause an osteoblastic reaction when grown in bone. Taken together, these results suggest that AR-regulated WNT7B signaling is critical for the growth of CRPC and development of the osteoblastic bone response characteristic of advanced prostate cancer. PMID:23386686

Zheng, Dali; Decker, Keith F.; Zhou, Tianhua; Chen, Jianquan; Qi, Zongtai; Jacobs, Kathryn; Weilbaecher, Katherine N.; Corey, Eva; Long, Fanxin; Jia, Li

2014-01-01

137

Venus Cloud Particle Size Distributions and Altitudes from IRTF/SpeX Spectral Image Cubes  

NASA Astrophysics Data System (ADS)

Absorption of infrared radition at 1.10, 1.18, 1.31, 1.74, and 2.3 ?m due to molecular gas electronic transitions is minimal through the Venus atmosphere. Blackbody radiation from the surface and deep atmosphere, observed on the night side, is therefore mostly affected by cloud aerosols. Ratios of the observed fluxes in each of these windows provide information on the scatterers’ sizes. Altitudes can be derived by the use of forward modeling to simulate the observed temperatures and fluxes. We use IRTF/SpeX spectra of the nightside of Venus we obtained in July and September 2007, simultaneous with Venus Express VIRTIS observations of the southern hemisphere at the same wavelengths. By allowing the 60” spectrometer slit to drift across Venus’ night side over approximately 15 minutes, we acquired spectral image cubes comprised of about 100 spectra, from 0.8 to 2.5 ?m with a spectral resolution of R 400. We use a multiple scattering line-by-line radiative transfer code and the HITRAN 2004 and HITEMP databases to calculate the fluxes in each window for a range of cloud structure and altitudes. Ratios of fluxes in each of the windows that are diagnostic of cloud particle distributions are compared with these ratios in our spectral image cubes. By obtaining a least squares best fit to the data, we produce maps of particle sizes and altitudes of the Venus clouds.

Bullock, Mark Alan; Young, E. F.; McGouldrick, K.

2009-09-01

138

Determination of thyroid hormones and their metabolites in tissue using SPE UPLC-tandem MS.  

PubMed

A solid-phase liquid chromatography tandem mass spectrometry (SPE LC-MS/MS) method was developed to determine thyroid hormones and their metabolites in tissue samples. The separation was achieved using reversed-phase ultra-performance liquid chromatography (UPLC); the mass spectrometric detection was achieved by positive electrospray ionization and multiple reaction monitoring. Prior to the UPLC separation a sample cleanup with a cation exchange was performed. ¹³C? labeled internal standards were used for the thyroid hormones and their metabolites. The method was linear over a range from 0.23 to 90?nmol/L for thyroxine and from 0.23 to 9?nmol/L for the metabolites. The lower limit of quantification ranged from 0.98 to 1.73?pg on column. Intra- and total assay variation were <10 and <15%, respectively. This method enables us to link thyroid hormone tissue concentrations to local iodothyronine deiodinase expressions, which will enhance our understanding of the regulation of thyroid hormone metabolism on the tissue level. PMID:21877326

Ackermans, M T; Kettelarij-Haas, Y; Boelen, A; Endert, E

2012-04-01

139

Saponin B, a novel cytostatic compound purified from Anemone taipaiensis, induces apoptosis in a human glioblastoma cell line.  

PubMed

Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Saponin B, a novel compound isolated from the medicinal plant, Anemone taipaiensis, has been found to have a strong time- and dose-dependent cytostatic effect on human glioma cells and to suppress the growth of U87MG GBM cells. In this study, we investigated whether saponin B induces the apoptosis of glioblastoma cells and examined the underlying mechanism(s) of action of saponin B. Saponin B signi?cantly suppressed U87MG cell proliferation. Flow cytometric analysis of DNA in the U87MG cells con?rmed that saponin B blocked the cell cycle at the S phase. Furthermore, treatment of the U87MG cells with saponin B induced chromatin condensation and led to the formation of apoptotic bodies, as observed under a ?uorescence microscope, and Annexin V/PI assay further suggested that phosphatidylserine (PS) externalization was apparent at higher drug concentrations. Treatment with saponin B activated the receptor-mediated pathway of apoptosis, as western blot analysis revealed the activation of Fas-l. Saponin B increased the Bax and caspase-3 ratio and decreased the protein expression of Bcl-2. The results from the present study demonstrate that the novel compound, saponin B, effectively induces the apoptosis of GBM cells and inhibits glioma cell growth and survival. Therefore, saponin B may be a potential candidate for the development of novel cancer therapeutics with antitumor activity against gliomas. PMID:24048272

Wang, Yuangang; Tang, Haifeng; Zhang, Yun; Li, Juan; Li, Bo; Gao, Zhenhui; Wang, Xiaoyang; Cheng, Guang; Fei, Zhou

2013-11-01

140

CORRTEX Diagnostic Deployment for the SPE-III experiment, 24 July 2012: Fielding Report and Preliminary Data Analysis  

SciTech Connect

The Continuous Reflectometry for Radius vs Time Experiments (CORRTEX) diagnostic system was deployed for the third explosives test in the Source Physics Experiment (SPE) sequence to monitor and verify several conditions of the experiment including the detonation velocity of the explosive package and functioning of explosive initiators. Six distance-marked coaxial cables were installed on the SPE-III explosives canister, and key locations documented through along-cable length measurements and photography. CORRTEX uses electrical-pulse time-domain reflectometry to continuously record the two-way transit time (TWTT) of the cables. As the shock front of the detonation advances, the coaxial cable is shorted or destroyed, and the resulting TWTT also decreases. Interpretation of these changes as a function of TWTT can be converted to positional measurements using known parameters of the cables.

Sandoval, Thomas D. [Los Alamos National Laboratory; Schultz-Fellenz, Emily S. [Los Alamos National Laboratory

2012-08-29

141

Identification of the major constituents of Hypericum perforatum by LC\\/SPE\\/NMR and\\/or LC\\/MS  

Microsoft Academic Search

The newly established hyphenated instrumentation of LC\\/DAD\\/SPE\\/NMR and LC\\/UV\\/(ESI)MS techniques have been applied for separation and structure verification of the major known constituents present in Greek Hypericum perforatum extracts. The chromatographic separation was performed on a C18 column. Acetonitrile-water was used as a mobile phase. For the on-line NMR detection, the analytes eluted from column were trapped one by one

Evangelos C. Tatsis; Sjef Boeren; Vassiliki Exarchou; Anastassios N. Troganis; Jacques Vervoort; Ioannis P. Gerothanassis

2007-01-01

142

An evaluation of antifouling booster biocides in Gran Canaria coastal waters using SPE-LC MS\\/MS  

Microsoft Academic Search

A solid phase extraction (SPE) technique for seawater samples coupled to quantification using liquid chromatography tandem-mass spectrometry (LC-MS\\/MS) is described to quantify relevant antifouling booster biocides of ecotoxicological concern (Diuron, TCMTB, Irgarol 1051 and Dichlofluanid). The optimised methodology provides a sensitive, easy to use and efficient analytical procedure with detection limits in the range of between 0.1 and 0.2?ng?L and

Álvaro Sánchez Rodríguez; Zoraida Sosa Ferrera; José Juan Santana Rodríguez

2011-01-01

143

Regulation of Apoptosis by Inhibitors of Apoptosis (IAPs)  

PubMed Central

Abstract Inhibitors of Apoptosis (IAPs) are a family of proteins with various biological functions including regulation of innate immunity and inflammation, cell proliferation, cell migration and apoptosis. They are characterized by the presence of at least one N-terminal baculoviral IAP repeat (BIR) domain involved in protein-protein interaction. Most of them also contain a C-terminal RING domain conferring an E3-ubiquitin ligase activity. In drosophila, IAPs are essential to ensure cell survival, preventing the uncontrolled activation of the apoptotic protease caspases. In mammals, IAPs can also regulate apoptosis through controlling caspase activity and caspase-activating platform formation. Mammalian IAPs, mainly X-linked IAP (XIAP) and cellular IAPs (cIAPs) appeared to be important determinants of the response of cells to endogenous or exogenous cellular injuries, able to convert the survival signal into a cell death-inducing signal. This review highlights the role of IAP in regulating apoptosis in Drosophila and Mammals. PMID:24709650

Berthelet, Jean; Dubrez, Laurence

2013-01-01

144

Regulation of Apoptosis by Inhibitors of Apoptosis (IAPs).  

PubMed

Inhibitors of Apoptosis (IAPs) are a family of proteins with various biological functions including regulation of innate immunity and inflammation, cell proliferation, cell migration and apoptosis. They are characterized by the presence of at least one N-terminal baculoviral IAP repeat (BIR) domain involved in protein-protein interaction. Most of them also contain a C-terminal RING domain conferring an E3-ubiquitin ligase activity. In drosophila, IAPs are essential to ensure cell survival, preventing the uncontrolled activation of the apoptotic protease caspases. In mammals, IAPs can also regulate apoptosis through controlling caspase activity and caspase-activating platform formation. Mammalian IAPs, mainly X-linked IAP (XIAP) and cellular IAPs (cIAPs) appeared to be important determinants of the response of cells to endogenous or exogenous cellular injuries, able to convert the survival signal into a cell death-inducing signal. This review highlights the role of IAP in regulating apoptosis in Drosophila and Mammals. PMID:24709650

Berthelet, Jean; Dubrez, Laurence

2013-01-01

145

Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans  

PubMed Central

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NF?B induction. Proteins involved in apoptosis and NF?B induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NF?B-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families. PMID:12819136

Reed, John C.; Doctor, Kutbuddin; Rojas, Ana; Zapata, Juan M.; Stehlik, Christian; Fiorentino, Loredana; Damiano, Jason; Roth, Wilfried; Matsuzawa, Shu-ichi; Newman, Ruchi; Takayama, Shinichi; Marusawa, Hiroyuki; Xu, Famming; Salvesen, Guy; Godzik, Adam

2003-01-01

146

Caffeic Acid Phenethyl Ester Protects against Amphotericin B Induced Nephrotoxicity in Rat Model  

PubMed Central

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10??mol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50?mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10??mol/kg CAPE i.p. and one dose of 50?mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models. PMID:25032223

Altuntas, Atila; Y?lmaz, H. Ramazan; Altuntas, Aysegul; Uz, Efkan; Demir, Murat; Gokcimen, Alparslan; Aksu, Oguzhan; Bayram, Dilek Senol; Sezer, Mehmet Tugrul

2014-01-01

147

APOPTOSIS IN WHOLE MOUSE OVARIES  

EPA Science Inventory

Apoptosis in Whole Mouse Ovaries Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711....

148

Genetic Inactivation of an Extracellular Cysteine Protease (SpeB) Expressed by Streptococcus pyogenes Decreases Resistance to Phagocytosis and Dissemination to Organs  

Microsoft Academic Search

Streptococcal pyrogenic exotoxin B (SpeB), a conserved cysteine protease expressed by virtually all Strepto- coccus pyogenes strains, has recently been shown to be an important virulence factor (S. Lukomski, S. Sreevat- san, C. Amberg, W. Reichardt, M. Woischnik, A. Podbielski, and J. M. Musser, J. Clin. Invest. 99:2574-2580, 1997). Genetic inactivation of SpeB significantly decreased the lethality of a serotype

SLAWOMIR LUKOMSKI; EUGENE H. BURNS; PHILIP R. WYDE; ANDREAS PODBIELSKI; JACQUELINE RURANGIRWA; DONNA K. MOORE-POVEDA; JAMES M. MUSSER

1998-01-01

149

Apoptosis in Acute Kidney Injury  

Microsoft Academic Search

Acute kidney injury (AKI), also called acute renal failure, is a major kidney disease associated with high mortality. Under\\u000a the disease condition, renal tubular cells are reversibly or irreversibly injured, undergoing cell death in both forms of\\u000a necrosis and apoptosis. Research during the last few years has established an important role for tubular cell apoptosis in\\u000a ischemic as well as

Navjotsingh Pabla; Qingqing Wei; Zheng Dong

150

[Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells].  

PubMed

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma. PMID:23984518

Xu, Qiu-Ju; Hou, Li-Li; Hu, Guo-Qiang; Xie, Song-Qiang

2013-06-01

151

Optimization of a pre-MEKC separation SPE procedure for steroid molecules in human urine samples.  

PubMed

Many steroid hormones can be considered as potential biomarkers and their determination in body fluids can create opportunities for the rapid diagnosis of many diseases and disorders of the human body. Most existing methods for the determination of steroids are usually time- and labor-consuming and quite costly. Therefore, the aim of analytical laboratories is to develop a new, relatively low-cost and rapid implementation methodology for their determination in biological samples. Due to the fact that there is little literature data on concentrations of steroid hormones in urine samples, we have made attempts at the electrophoretic determination of these compounds. For this purpose, an extraction procedure for the optimized separation and simultaneous determination of seven steroid hormones in urine samples has been investigated. The isolation of analytes from biological samples was performed by liquid-liquid extraction (LLE) with dichloromethane and compared to solid phase extraction (SPE) with C18 and hydrophilic-lipophilic balance (HLB) columns. To separate all the analytes a micellar electrokinetic capillary chromatography (MECK) technique was employed. For full separation of all the analytes a running buffer (pH 9.2), composed of 10 mM sodium tetraborate decahydrate (borax), 50 mM sodium dodecyl sulfate (SDS), and 10% methanol was selected. The methodology developed in this work for the determination of steroid hormones meets all the requirements of analytical methods. The applicability of the method has been confirmed for the analysis of urine samples collected from volunteers--both men and women (students, amateur bodybuilders, using and not applying steroid doping). The data obtained during this work can be successfully used for further research on the determination of steroid hormones in urine samples. PMID:24232737

Ol?dzka, Ilona; Kowalski, Piotr; Dziomba, Szymon; Szmudanowski, Piotr; B?czek, Tomasz

2013-01-01

152

Geologic Assessment of the Damage Zone from the Second Test at Source Physics Experiment-Nevada (SPE-N)  

SciTech Connect

The National Center for Nuclear Security (NCNS), established by the U.S. Department of Energy, National Nuclear Security Administration, is conducting a series of explosive tests at the Nevada National Security Site (NNSS; formerly the Nevada Test Site) that are designed to increase the understanding of certain basic physical phenomena associated with underground explosions. These tests will aid in developing technologies that might be used to detect underground nuclear explosions in support of verification activities for the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The initial NCNS project is a series of explosive tests, known collectively as the Source Physics Experiment at the NNSS (SPE-N), being conducted in granitic rocks at the Climax stock in northern Yucca Flat. The SPE-N test series is designed to study the generation and propagation of seismic waves. The data will be used to improve the predictive capability of calculational models for detecting and characterizing underground explosions. The first SPE-N test (SPE-N-1) was a “calibration” shot conducted in May 2011, using 100 kilograms (kg) of explosives at the depth of 54.9 meters (m) (180 feet [ft]) in the U-15n source hole. SPE-N-2 was conducted in October 2011, using 1,000 kg of explosives at the depth of 45.7 m (150 ft) in the same source hole. Following the SPE-N-2 test, the core hole U-15n#10 was drilled at an angle from the surface to intercept the SPE-N-2 shot point location to obtain information necessary to characterize the damage zone. The desire was to determine the position of the damage zone near the shot point, at least on the northeast side, where the core hole penetrated it. The three-dimensional shape and symmetry of the damage zone are unknown at this time. Rather than spherical in shape, the dimensions of the damage zone could be influenced by the natural fracture sets in the vicinity. Geologic characterization of the borehole included geophysical logging, a directional survey, and geologic description of the core to document visual evidence of damage. Selected core samples were provided to Sandia National Laboratories (SNL) for laboratory tests (to be reported by SNL). A significant natural fault zone was encountered in the U-15n#10 angle core hole between the drilled depths of 149 and 155 ft (straight-line distance or range station [RS] from the shot point of 7.5 to 5.7 m). However, several of the fractures observed in the U-15n#10 hole are interpreted as having been caused by the explosion. These fractures are characterized by a “fresh,” mechanically broken look, with uncoated and very irregular surfaces. They tend to terminate against natural fractures and have orientations that differ from the previously defined natural fracture sets. The most distant fracture from the shot point that could be interpreted as having been caused by the explosion was seen at approximately RS 10.0 m. No other possibly explosion-induced fractures are apparent above the fault, but are common starting at RS 5.4 m, which is below the fault. It is unknown how the fault zone might have affected the propagation of seismic waves or how the materials in the fault zone (altered granite, breccia, gouge) were affected by the explosion. From RS 3.3 m to the end of the recovered core at RS 1.6 m, some of the core samples are softer and lighter in color, but do not appear to be weathered. It is thought this could be indicative of the presence of distributed microfracturing.

,

2012-09-18

153

[Lysosomes and apoptosis].  

PubMed

In 1955, Christian de Duve and his coworkers from the School of Medicine in Louvain, Belgium, named a group of cytoplasmic formations surrounded by lipoprotein membrane and containing acid hydrolase enzymes as lysosomes. Biochemical and cytochemical studies showed lysosomes to be found in animal and vegetable eukaryotic cells. Later on, lysosomes were found to be involved in the dynamics of lysosomal system, which consists of a number of various cytoplasmic formations such as primary and secondary lysosomes, endosomes, autophagosomes and postlysosomes. These formations are inter-connected by the mechanism of membrane integration, and in some instances by the cell membrane. Lysosomal system is involved in numerous physiological processes such as degradation of endogenous and exogenous macromolecules (proteins, lipids, polysaccharides and nucleic acids), cytoplasmic formations (mitochondria, peroxisomes, Golgi complex) that have performed their functions, tissue regression (post-lactation mammary gland), hormone secretion regulation (proinsulin to insulin), etc. On the other hand, lysosomal system is also involved in a number of pathologic processes like inflammation, allergic reactions, ischemia, hypoxia, as well as in lysosomal diseases (thesaurismoses), e.g., type II glycogenosis, fucosidosis, mucolipidosis III, etc. In 1974, Christian de Duve introduced the term lysosomotropism, denoting entry of the pharmacologically active, toxic and carcinogenic substances in the lysosomal system irrespective of their chemical nature and mechanism of input. Lysosomotropic substances may act in two ways: (1) causing impairments in the intralysosomal area, with toxic manifestations; and (2) modifying their membrane properties by increasing or decreasing membrane permeability, or by inducing labilizing or stabilizing effects. Damage to the lysosomal system occurs in the late stage of necrosis, while destabilization of lysosomal formations has been recorded in primary processes during apoptosis. PMID:19999542

Viki?-Topi?, Drazen; Carevi?, Olga

2009-10-01

154

Apoptosis in rheumatoid arthritis synovium.  

PubMed Central

RA synovial tissue (ST) was studied to determine if and where apoptosis occurs in situ. Genomic DNA was extracted from 5 RA and 1 osteoarthritis ST samples. Agarose gel electrophoresis demonstrated DNA ladders characteristic for apoptosis from each tissue. In situ and labeling (ISEL) was used to identify DNA strand breaks consistent with apoptosis in frozen sections. 12 RA and 4 osteoarthritis ST were studied by ISEL and all were positive, but only 2 of 4 normal tissues were positive. The primary location of apopotic cells was the synovial lining. Some sublining cells were also positive, but lymphoid aggregate staining was conspicuously absent. Immunohistochemistry and ISEL were combined and showed that the lining cells with DNA strand breaks were mainly macrophages, although some fibroblastlike cells were also labeled. Sublining cells with fragmented DNA included macrophages and fibroblasts, but T cells in lymphoid aggregates, which expressed large amounts of bcl-2, were spared. DNA strand breaks in cultured fibroblastlike synoviocytes was assessed using ISEL. Apoptosis could be induced by actinomycin D, anti-fas antibody, IL-1, and TNF-alpha but not by IFN-gamma. Fas expression was also detected on fibroblast-like synoviocytes using flow cytometry. Therefore, DNA strand breaks occur in synovium of patients with arthritis. Cytokines regulate this process, and the cytokine profile in RA (high IL-1/TNF; low IFN-gamma) along with local oxidant injury might favor induction of apoptosis. Images PMID:7657832

Firestein, G S; Yeo, M; Zvaifler, N J

1995-01-01

155

Apoptosis of Airway Epithelial Cells  

PubMed Central

LL-37 is a human cationic host defense peptide that is present in the specific granules of neutrophils, produced by epithelial cells from a variety of tissues, and is upregulated during inflammation, infection, and injury. It has been proposed to have a variety of antimicrobial functions, including both direct antimicrobial activity and immunomodulatory functions. Using the TUNEL assay it was demonstrated that LL-37 induced apoptosis in vitro in the A549 human lung and 16HBE4o- human airway epithelial cell lines, and in vivo in the murine airway. Peptide-induced apoptosis in vitro involved the activation of caspase pathways and was substantially inhibited by an inhibitor of caspase 3. Apoptosis was also inhibited by human serum, but not fetal bovine serum. Similarly, human but not fetal bovine serum inhibited the cellular internalization of LL-37 and the production of IL-8 in response to LL-37 treatment of epithelial cells. The protective effects of human serum were also observed with high-density lipoproteins but not by the core peptide apolipoprotein A1, providing one possible mechanism of human serum inhibition of apoptosis. We propose that LL-37–induced apoptosis of epithelial cells at low serum tissue sites may have a protective role against bacterial infection. PMID:16340000

Lau, Y. Elaine; Bowdish, Dawn M. E.; Cosseau, Celine; Hancock, Robert E. W.; Davidson, Donald J.

2010-01-01

156

Simple SPE-HPLC determination of some common drugs and herbicides of environmental concern by pulsed amperometry.  

PubMed

In this work the electrochemical behavior of substances of environmental concern [bentazone, atrazine, carbamazepine, phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin, HPPH] on a glassy carbon working electrode (Ag/AgCl reference electrode) was studied with the aim to develop a HPLC method coupled with amperometric detection. Constant potential (DC), pulsed amperometric detection modes were studied. For the pulsed mode, several waveforms were set and investigated. Detection conditions were optimized as a function of eluent pH. In order to reduce the limits of detection and to analyze natural water samples, a SPE protocol was optimized to be coupled to the developed procedure. For this aim, five sorbents of different physico-chemical characteristics were tested optimizing a recovery procedure for each of the cartridge evaluated. At the optimized SPE conditions, recoveries were included in the range (R=90.2-100.5% for all the analytes, with excellent reproducibility (<%, n=3). The method detection limits obtained by pulsed amperometry after the SPE protocol (preconcentration factor 100) were 113ngL(-1) (0.47nmolL(-1)), 67ngL(-1) (0.25nmolL(-1)), 234ngL(-1) (1.1nmolL(-1)), for bentazone, HPPH and carbamazepine, respectively. Robustness of the method was assessed for each analyte at a concentration level corresponding to about three times the limit of detection, through the evaluation of intra-day (n=13) and inter-day tests (4 days, n=52). Finally the method was successfully applied for the analysis of a river sample (Po River, Turin, Italy). PMID:25281094

Rivoira, L; De Carlo, R M; Cavalli, S; Bruzzoniti, M C

2015-01-01

157

Development of colorimetric solid Phase Extraction (C-SPE) for in-flight Monitoring of spacecraft Water Supplies  

SciTech Connect

Although having recently been extremely successful gathering data on the surface of Mars, robotic missions are not an effective substitute for the insight and knowledge about our solar system that can be gained though first-hand exploration. Earlier this year, President Bush presented a ''new course'' for the U.S. space program that shifts NASA's focus to the development of new manned space vehicles to the return of humans to the moon. Re-establishing the human presence on the moon will eventually lead to humans permanently living and working in space and also serve as a possible launch point for missions into deeper space. There are several obstacles to the realization of these goals, most notably the lack of life support and environmental regeneration and monitoring hardware capable of functioning on long duration spaceflight. In the case of the latter, past experience on the International Space Station (ISS), Mir, and the Space Shuttle has strongly underscored the need to develop broad spectrum in-flight chemical sensors that: (1) meet current environmental monitoring requirements on ISS as well as projected requirements for future missions, and (2) enable the in-situ acquisition and analysis of analytical data in order to further define on-orbit monitoring requirements. Additionally, systems must be designed to account for factors unique to on-orbit deployment such as crew time availability, payload restrictions, material consumption, and effective operation in microgravity. This dissertation focuses on the development, ground testing, and microgravity flight demonstration of Colorimetric Solid Phase Extraction (C-SPE) as a candidate technology to meet the near- and long-term water quality monitoring needs of NASA. The introduction will elaborate further on the operational and design requirements for on-orbit water quality monitoring systems by discussing some of the characteristics of an ''ideal'' system. A description of C-SPE and how the individual components of the platform are combined to satisfy many of these requirements is then presented, along with a literature review on the applications of C-SPE and similar sorption-spectrophotometric techniques. Finally, a brief overview of diffuse reflection spectroscopy and the Kubelka-Munk function, which are used to quantify analytes via C-SPE, is presented.

Daniel Bryan Gazda

2004-12-19

158

Molecular mechanisms of hepatic apoptosis  

PubMed Central

Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Mechanisms of hepatic apoptosis are complicated by multiple signaling pathways. The progression of liver disease is affected by the balance between apoptotic and antiapoptotic capabilities. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis. PMID:24434519

Wang, K

2014-01-01

159

Apoptosis: Targets in Pancreatic Cancer  

PubMed Central

Pancreatic adenocarcinoma is characterized by poor prognosis, because of late diagnosis and lack of response to chemo- and/or radiation therapies. Resistance to apoptosis mainly causes this insensitivity to conventional therapies. Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Certain genetic disturbances of apoptotic signaling pathways have been found in carcinomas leading to tumor development and progression. In the past few years, the knowledge about the complex pathways of apoptosis has strongly increased and new therapeutic approaches based on this knowledge are being developed. This review will focus on the role of apoptotic proteins contributing to pancreatic cancer development and progression and will demonstrate possible targets to influence this deadly disease. PMID:12605713

Westphal, Sabine; Kalthoff, Holger

2003-01-01

160

Organopalladium compound 7b targets mitochondrial thiols and induces caspase-dependent apoptosis in human myeloid leukemia cells  

PubMed Central

The advances in the treatment of chronic myeloid leukemia (CML) during the last years were also accompanied by the development of evading strategies by tumor cells, resulting in chemotherapy resistance in some patients. Patented organopalladium compounds derived from the reaction of N,N-dimethyl-1-phenethylamine (dmpa) with [1,2-ethanebis(diphenylphosphine)] (dppe) exhibited a potent antitumor activity in vivo and in vitro in melanoma cells. We showed here that the cyclopalladated derivative [Pd2(R(+))C2, N-dmpa)2(?-dppe)Cl2], named compound 7b, was highly effective to promote cell death in the K562 human leukemia cells and its mechanisms of action were investigated. It was shown that compound 7b was able to promote exclusively apoptotic cell death in K562 cells associated to cytochrome c release and caspase 3 activation. This cytotoxic effect was not observed in normal peripheral mononuclear blood cells. The compound 7b-induced intrinsic apoptotic pathway was triggered by the protein thiol oxidation that resulted in the dissipation of the mitochondrial transmembrane potential. The preventive effect of the dithiothreitol on the compound 7b-induced cell death and all downstream events associated to apoptosis confirmed that death signal was elicited by the thiol oxidation. These findings contribute to the elucidation of the palladacycle 7b-induced cell death mechanism and present this compound as a promising drug in the CML antitumor chemotherapy. PMID:23744358

Moraes, V W R; Caires, A C F; Paredes-Gamero, E J; Rodrigues, T

2013-01-01

161

Caspases: the executioners of apoptosis.  

PubMed Central

Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1 beta-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P1 position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide active-site motif. Capases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of critical cellular substrates, including poly(ADP-ribose) polymerase and lamins, so precipitating the dramatic morphological changes of apoptosis. Apoptosis induced by CD95 (Fas/APO-1) and tumour necrosis factor activates caspase-8 (MACH/FLICE/Mch5), which contains an N-terminus with FADD (Fas-associating protein with death domain)-like death effector domains, so providing a direct link between cell death receptors and the caspases. The importance of caspase prodomains in the regulation of apoptosis is further highlighted by the recognition of adapter molecules, such as RAIDD [receptor-interacting protein (RIP)-associated ICH-1/CED-3-homologous protein with a death domain]/CRADD (caspase and RIP adapter with death domain), which binds to the prodomain of caspase-2 and recruits it to the signalling complex. Cells undergoing apoptosis following triggering of death receptors execute the death programme by activating a hierarchy of caspases, with caspase-8 and possibly caspase-10 being at or near the apex of this apoptotic cascade. PMID:9337844

Cohen, G M

1997-01-01

162

Regulation of SpeB in Streptococcus pyogenes by pH and NaCl: a Model for In Vivo Gene Expression†  

PubMed Central

For a pathogen such as Streptococcus pyogenes, ecological success is determined by its ability to sense the environment and mount an appropriate adaptive transcriptional response. Thus, determining conditions for analyses of gene expression in vitro that are representative of the in vivo environment is critical for understanding the contributions of transcriptional response pathways to pathogenesis. In this study, we determined that the gene encoding the SpeB cysteine protease is up-regulated over the course of infection in a murine soft-tissue model. Conditions were identified, including growth phase, acidic pH, and an NaCl concentration of <0.1 M, that were required for expression of speB in vitro. Analysis of global expression profiles in response to these conditions in vitro identified a set of coregulated genes whose expression patterns showed a significant correlation with that of speB when examined during infection of murine soft tissues. This analysis revealed that a culture medium that promotes high levels of SpeB expression in vitro produced an expression profile that showed significant correlation to the profile observed in vivo. Taken together, these studies establish culture conditions that mimic in vivo expression patterns; that growth phase, pH, and NaCl may mimic relevant cues sensed by S. pyogenes during infection; and that identification of other environmental cues that alter expression of speB in vitro may provide insight into the signals that direct global patterns of gene expression in vivo. PMID:16385029

Loughman, Jennifer A.; Caparon, Michael

2006-01-01

163

HSV-Induced Apoptosis in Herpes Encephalitis  

Microsoft Academic Search

HSV triggers and blocks apoptosis in cell type-specific fashion. This review discusses present understanding of the role of apoptosis and signaling cascades in neuronal pathogenesis and survival and summarizes present findings relating to the modulation of these strictly balanced processes by HSV infection. Underscored are the findings that HSV-1, but not HSV-2, triggers apoptosis in CNS neurons and causes encephalitis

L. Aurelian

164

Apoptosis: the physiologic pathway of cell death.  

PubMed

Physiologic roles of apoptosis may be subverted in pathologic processes. Apoptotic control of lymphocyte overproduction, for example, protects against cancer and autoimmunity, but in a disease such as AIDS, helper T cells may be programmed for suicide rather than an immune response. Drugs could be designed to limit apoptosis in AIDS or myocardial infarction or to promote apoptosis of tumor cells. PMID:7902840

Cohen, J J

1993-12-15

165

Apoptosis induced by bovine ephemeral fever virus  

Microsoft Academic Search

The potential significance of bovine ephemeral fever virus (BEFV)-induced apoptosis and involved viral molecules was fully unknown. In the present study, evidence is provided demonstrating that bovine ephemeral fever virus induces apoptosis in several cell lines. Five types of assays for apoptosis were used in examining BEFV-infected cells. (1) Assay for DNA fragmentation, (2) nuclear staining with acridine orange, (3)

Chia J. Chang; Wen L. Shih; Feng L. Yu; Ming H. Liao; Hung J. Liu

2004-01-01

166

Simultaneous determination of selected endocrine disrupters (pesticides, phenols and phthalates) in water by in-field solid-phase extraction (SPE) using the prototype PROFEXS followed by on-line SPE (PROSPEKT) and analysis by liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry  

Microsoft Academic Search

In this study, a new procedure, based on on-line solid-phase extraction (SPE) and analysis by liquid-chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS), has been developed for the simultaneous, multianalyte determination of 21 selected pesticides, phenols and phthalates in water. SPE was carried out on polymeric PLRP-s cartridges by percolating 20 mL-samples. For sample preconcentration, the performance of a prototype programmable field extraction

P. López-Roldán; M. J. López de Alda; D. Barceló

2004-01-01

167

Graphene as an efficient sorbent for the SPE of organochlorine pesticides in water samples coupled with GC-MS.  

PubMed

The determination of organochlorine pesticides in water samples, which are harmful to humans, is very important for environmental risk assessment. Based on the excellent adsorption properties of graphene, an SPE coupled with GC-MS method for the monitoring of organochlorines (four hexachlorcyclohexanes and four dichlorodiphenyltrichloroethanes) was developed. Owing to the hydrophobic interaction and ?-? stacking interaction between the analytes and graphene, the analytes quantitatively adsorbed onto the graphene-based SPE cartridge were eluted by ethyl acetate for analysis. Several parameters influencing the analytical performance, such as the kind of elution, sample volume, reusability of the cartridge, have been investigated in detail. Under the optimal conditions, detection of limits of 1.95-9.38 ng/L, recoveries of 83.9-107.3% at two spiked concentration levels (0.1 and 10 ng/mL) and RSDs in the range of 2.9-7.4% for real water samples were obtained for all the analytes. This work reveals the great potential of graphene in sample preparation procedures. PMID:23983172

Han, Qiang; Wang, Zonghua; Xia, Jianfei; Xia, Linhua; Chen, Sha; Zhang, Xiaoqiong; Ding, Mingyu

2013-11-01

168

An automated SPE/LC/MS/MS method for the analysis of cocaine and metabolites in whole blood.  

PubMed

As laboratories are called upon to develop novel, fast, and sensitive methods, here we present a completely automated method for the analysis of cocaine and its metabolites (benzoylecgonine, ecgonine methyl ester, ecgonine and cocaethylene) from whole blood. This method utilizes an online solid-phase extraction (SPE) with high performance liquid chromatographic separation and tandem mass spectrometric detection. Pretreatment of samples involve only protein precipitation and ultracentrifugation. An efficient online solid-phase extraction (SPE) procedure was developed using Hysphere MM anion sorbent. A gradient chromatography method with a Gemini C6-Phenyl (50mmx3.00mm i.d., 5microm) column was used for the complete separation of all components. Analysis was by positive ion mode electrospray ionization tandem mass spectrometry, using multiple reaction monitoring (MRM) to enhance the selectivity and sensitivity of the method. For the analysis, two MRM transitions are monitored for each analyte and one transition is monitored for each internal standard. With a 30-microL sample injection, linearity was analyte dependent but generally fell between 8 and 500ng/mL. The limits of detection (LODs) for the method ranged from 3 to 16ng/mL and the limits of quantitation (LOQs) ranged from 8 to 47ng/mL. The bias and precision were determined using a simple analysis of variance (ANOVA: single factor). The results demonstrate bias as <7%, and %precision as <9% for all components at each QC level. PMID:18829399

Jagerdeo, Eshwar; Montgomery, Madeline A; Lebeau, Marc A; Sibum, Martin

2008-10-15

169

Herbal medicines and infectious diseases: characterization by LC-SPE-NMR of some medicinal plant extracts used against malaria.  

PubMed

The extracts of two medicinal plants used in traditionalmedicine against malariawere characterized by means of an LC?SPE?NMR and LC?MS platform. The structure of a series of major constituents from Bafodeya benna, as well as minor constituents from Ormocarpum kirkii, was determined. Bafodeya benna was found to contain (2R,3R)-taxifolin-3-O-?-L-rhamnoside or astilbin, and its isomers neoastilbin, neoisoastilbin, and isoastilbin, as well as quercetin-3-O-?-L-rhamnoside. From Ormocarpum kirkii, a series of known flavonoids and biflavonoids was obtained, as well as three new compounds, i.e., 7,7??-di-O-?-D-glucosyl-(?)-chamaejasmin, 7-O-?-D-glucosyl-(I-3,II-3)-biliquiritigenin, and isovitexin-(I-3,II-3)-naringenin. The isolated constituents may explain, at least in part, the traditional use against malaria. LC?SPE?NMR, in combination with LC?MS, is a powerful tool for the fast characterization of plant extracts, in order to define priorities at an early stage of a fractionation procedure. In addition, herbal medicinal products can completely be characterized, both with regard to their major as well as their minor constituents. PMID:21328178

Xu, Yong-Jiang; Capistrano, Rica; Dhooghe, Liene; Foubert, Kenn; Lemière, Filip; Maregesi, Sheila; Baldé, Aliou; Apers, Sandra; Pieters, Luc

2011-07-01

170

SPE of 5-lipoxygenase metabolites and the effect of head-column field-amplified sample stacking in MEKC.  

PubMed

The SPE of leukotrienes and eicosatetraenoic acids using anion exchange materials was compared to the classical extraction with C18 columns. A silica-based strong anion exchanger, a polymer-based weak anion exchanger, and a polymer-based mixed-mode strong anion exchanger were studied. All anion exchange materials displayed a higher recovery of the analytes with values between 70 and 90% when extracting standard solutions and analyzing by HPLC. The effect was less pronounced for the analysis of the compounds in incubations of polymorphonuclear leukocytes. Using MEKC with head-column field-amplified sample stacking for analyte quantification, much lower values of the peak areas were observed compared to the determination of the recovery of the analytes by HPLC. Using MEKC analysis, the highest values were found for the polymer-based weak anion exchange material, while values below 10% were found for the polymer-based mixed mode strong anion exchanger. This could be attributed to the presence of electrolytes in the eluates that compromised the stacking efficiency. The extent of residual electrolytes depended on the SPE protocol, resulting in large differences of the amount of analyte determined by MEKC when applying head-column field-amplified sample stacking for online analyte concentration. PMID:24039166

Abromeit, Hans; Wu, Fengyi; Scriba, Gerhard K E

2013-11-01

171

From retrospective assessment to prospective decisions in natural product isolation: HPLC-SPE-NMR analysis of Carthamus oxyacantha.  

PubMed

An extract of Carthamus oxyacantha (wild safflower) was investigated using two approaches: a traditional, nontarget fractionation by VLC and HPLC, and the hyphenated technique HPLC-PDA-HRMS-SPE-NMR followed by targeted isolation of selected constituents for inclusion in a screening library of pure natural products. While the nontarget fractionation involved considerable time spent on pursuing fractions containing well-known or undesired compounds, the hyphenated analysis was considerably faster and required less solvent and other consumables. The results were used to design and execute an optimized, HPLC-HRMS-guided, targeted isolation scheme aiming exclusively at a series of identified spiro compounds. Thus, HPLC-PDA-HRMS-SPE-NMR is a dereplication technique of choice, allowing economical acquisition of comprehensive data about compounds in crude extracts, which can be used for rational, prospective decisions about further isolation efforts. A total of 15 compounds were identified in the extract. Six spiro compounds, of which four have not previously been characterized, and tracheloside (a lignin glucoside) are presented with assigned 1H and 13C chemical shifts. PMID:22060189

Johansen, Kenneth T; Wubshet, Sileshi G; Nyberg, Nils T; Jaroszewski, Jerzy W

2011-11-28

172

Assessment of constituents in Allium by multivariate data analysis, high-resolution ?-glucosidase inhibition assay and HPLC-SPE-NMR.  

PubMed

Bulbs and leaves of 35 Allium species and cultivars bought or collected in 2010-2012 were investigated with multivariate data analysis, high-resolution ?-glucosidase inhibition assays and HPLC-HRMS-SPE-NMR with the aim of exploring the potential of Allium as a future functional food for management of type 2 diabetes. It was found that 30 out of 106 crude extracts showed more than 80% inhibition of the ?-glucosidase enzyme at a concentration of 40mg/mL (dry sample) or 0.4g/mL (fresh sample). High-resolution ?-glucosidase biochromatograms of these extracts allowed fast identification of three analytes with ?-glucosidase inhibitory activity, and subsequent HPLC-HRMS-SPE-NMR experiments allowed identification of these as N-p-coumaroyloctopamine, N-p-coumaroyltyramine, and quercetin. The distribution of these three compounds was mapped for all samples by HPLC-ESI-HRMS. Unsupervised principal component analysis of samples from 2012 indicated that a major difference between fresh material and dried material is the increased amount of quercetin, a known ?-glucosidase inhibitor. PMID:24837940

Schmidt, Jeppe S; Nyberg, Nils T; Staerk, Dan

2014-10-15

173

Abortive apoptosis in Alzheimer's disease  

Microsoft Academic Search

Multiple studies suggest that neuronal death in Alzheimer's disease (AD) is the result of an apoptotic mechanism. However, the stereotypical manifestations that define the terminal phases of apoptosis, such as chromatin condensation, apoptotic bodies, and blebbing, are not seen in AD. In this study, we show that the caspases, such as caspase 6, which cleave amyloid-# protein precursor (A#PP) and

Arun K. Raina; Ayala Hochman; Xiongwei Zhu; Catherine A. Rottkamp; Akihiko Nunomura; Sandra L. Siedlak; Heather Boux; Rudolph J. Castellani; George Perry; Mark A. Smith

2001-01-01

174

Targeting Apoptosis Signaling in Pancreatic Cancer  

PubMed Central

The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery. PMID:24212616

Fulda, Simone

2011-01-01

175

Diabetes and renal tubular cell apoptosis  

PubMed Central

Apoptosis contributes to the development of diabetic nephropathy, but the mechanism by which high glucose induces apoptosis is not fully understood. Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Hyperglycemia and high glucose in vitro also lead to apoptosis, a form of programmed cell death. High glucose similar to those seen with hyperglycemia in people with diabetes mellitus, lead to accelerated apoptosis, a form of programmed cell death characterized by cell shrinkage, chromatin condensation and DNA fragmentation, in variety of cell types, including renal proximal tubular epithelial cells. PMID:23593533

Habib, Samy L

2013-01-01

176

Inhibitory Effects of Resveratrol on Melanin Synthesis in Ultraviolet B-Induced Pigmentation in Guinea Pig Skin  

PubMed Central

Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits ?-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging. PMID:24596619

Lee, Taek Hwan; Seo, Jae Ok; Baek, So-Hyeon; Kim, Sun Yeou

2014-01-01

177

Liver myofibroblasts up-regulate monocyte CD163 expression via PGE2 during hepatitis B induced liver failure  

PubMed Central

Background Although patients with liver failure exhibit a generalized inflammatory-imbalance status, substantial evidence indicates that this immunosuppressive or anti-inflammatory state may be deleterious. Increased expression of CD163 (known to be involved in several anti-inflammatory functions of the immune system) in patients with liver failure is significantly correlated with a fatal outcome. However, little is known of the regulatory mechanisms that influence the expression of CD163. Methods We assessed the expression of CD163 on monocytes from both circulating cells and the liver tissues of patients with hepatitis B induced liver failure using flow cytometry and isolated the myofibroblasts from diseased livers. The ability of human liver myofibroblasts to regulate CD163 expression on monocytes was studied in vitro. Results We showed that CD163+ monocytes were enriched primarily in diseased livers and that they were associated with liver myofibroblasts in the same area. Accordingly, liver myofibroblasts were significantly superior to normal skin fibroblasts in inducing the expression of CD163 on monocytes in vitro. Moreover, we found that liver myofibroblasts triggered the activation of monocytes by secreting PGE2. Inhibition of PGE2 production in liver myofibroblasts using NS-398 markedly reduced CD163 expression in vitro. Conclusion These results suggest that liver myofibroblasts play a direct role in regulating the expression of CD163 on monocytes in human liver tissues and thereby may regulate monocyte function during hepatitis B induced liver failure. PMID:24597777

2014-01-01

178

Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses  

NASA Astrophysics Data System (ADS)

Histatins are human salivary gland peptides with anti-microbial and anti-inflammatory activities. In this study, we hypothesized that histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and attenuates HagB-induced chemokine responses in human myeloid dendritic cells. Histatin 5 bound to immobilized HagB in a surface plasmon resonance (SPR) spectroscopy-based biosensor system. SPR spectroscopy kinetic and equilibrium analyses, protein microarray studies, and I-TASSER structural modeling studies all demonstrated two histatin 5 binding sites on HagB. One site had a stronger affinity with a KD1 of 1.9 ?M and one site had a weaker affinity with a KD2 of 60.0 ?M. Binding has biological implications and predictive modeling studies and exposure of dendritic cells both demonstrated that 20.0 ?M histatin 5 attenuated (p < 0.05) 0.02 ?M HagB-induced CCL3/MIP-1?, CCL4/MIP-1?, and TNF? responses. Thus histatin 5 is capable of attenuating chemokine responses, which may help control oral inflammation.

Borgwardt, Derek S.; Martin, Aaron D.; van Hemert, Jonathan R.; Yang, Jianyi; Fischer, Carol L.; Recker, Erica N.; Nair, Prashant R.; Vidva, Robinson; Chandrashekaraiah, Shwetha; Progulske-Fox, Ann; Drake, David; Cavanaugh, Joseph E.; Vali, Shireen; Zhang, Yang; Brogden, Kim A.

2014-01-01

179

Apoptosis in virus infection dynamics models  

PubMed Central

In this paper, on the basis of the simplified two-dimensional virus infection dynamics model, we propose two extended models that aim at incorporating the influence of activation-induced apoptosis which directly affects the population of uninfected cells. The theoretical analysis shows that increasing apoptosis plays a positive role in control of virus infection. However, after being included the third population of cytotoxic T lymphocytes immune response in HIV-infected patients, it shows that depending on intensity of the apoptosis of healthy cells, the apoptosis can either promote or comfort the long-term evolution of HIV infection. Further, the discrete-time delay of apoptosis is incorporated into the pervious model. Stability switching occurs as the time delay in apoptosis increases. Numerical simulations are performed to illustrate the theoretical results and display the different impacts of a delay in apoptosis. PMID:24963975

Fan, Ruili; Dong, Yueping; Huang, Gang; Takeuchi, Yasuhiro

2014-01-01

180

The Domains of Apoptosis: A Genomics Perspective  

NSDL National Science Digital Library

Programmed cell death, also known as apoptosis, plays important roles in many aspects of normal physiology in animal species, including programmed death associated with fetal development or metamorphosis, tissue homeostasis, elimination of inappropriate cells in the immune system, and some aspects of aging. Defects in the regulation of apoptosis contribute to multiple diseases; for example, lack of apoptosis contributes to cancer, and excessive apoptosis is associated with neurodegenerative and autoimmune diseases. Apoptosis also functions as a defense mechanism against viruses and microbes. In the regulatory machinery that contols apoptosis, interactions between key proteins are determined by small protein segments or domains that allow cells to react appropriately to signals from within or outside the cell. In this Review, we examine the range of human proteins that contain these domains and discuss how the resultant protein interactions help control cell death. These same domains provide possible targets for the development of drugs that could beneficially modulate apoptosis.

John C. Reed (The Burnham Institute; REV); Kutbuddin S. Doctor (The Burnham Institute; REV); Adam Godzik (The Burnham Institute; REV)

2004-06-29

181

Phospolipase A2 and apoptosis.  

PubMed

Phospolipase A(2) (PLA(2)) is the esterase activity that cleaves the sn-2 ester bond in glycerophospholipids, releasing free fatty acids and lysophospholipids. The PLA(2) activity is found in a variety of enzymes which can be divided in several types based on their Ca(2+) dependence for their activity; Ca(2+)-dependent secretory phosholipases (sPLA(2)s) and cytosolic phospholipases (cPLA(2)s), and Ca(2+)-independent phospholipase A(2)s (iPLA(2)s). These enzymes also show diverse size and substrate specificity (i.e., in the fatty acid chain length and extent of saturation). Among the fatty acids released by PLA(2), arachidonic acid (AA) is of particular biological importance, because it is subsequently converted to prostanoids and leukotrienes by cyclooxygenases (COX) and lipoxygenases (LOX), respectively. Free AA may also stimulate apoptosis through activation of sphingomyelinase. Alternatively, it is suggested that oxidized metabolites generated from AA by LOX induce apoptosis. Although the precise mechanisms remain to be elucidated, changes are observed in glycerolipid metabolism during apoptotic processes. In some cells induced to undergo apoptosis, AA is released concomitant with loss of cell viability, caspase activation and DNA fragmentation. Such AA releases appear to be mediated by activation of cPLA(2) and/or iPLA(2). For example, tumor necrosis factor-alpha (TNF-alpha)-induced cell death is mediated by cPLA(2), whereas Fas-induced apoptosis appears to be mediated by iPLA(2). Some discrepancies among early experimental results were probably caused by differences in the experimental conditions such as the serum concentration, inhibitors used that are not necessarily specific to a single-type enzyme, or differential expression of each PLA(2) in cells employed in the experiments. Recent studies eliminated such problems, by carefully defining the experimental conditions, and using multiple inhibitors that show different specificities. Accordingly, more convincing data are available that demonstrate involvement of some PLA(2)s in the apoptotic processes. In addition to cPLA(2) and iPLA(2), sPLA(2)s were recently found to play roles in apoptosis. Moreover, new proteins that appear to control PLA(2)s are being discovered. Here, the roles of PLA(2)s in apoptosis are discussed by reviewing recent reports. PMID:12531539

Taketo, Makoto Mark; Sonoshita, Masahiro

2002-12-30

182

Inhibitors of apoptosis catch ubiquitin.  

PubMed

IAP (inhibitor of apoptosis) proteins are a class of anti-apoptotic regulators characterized by the presence of BIR (baculoviral IAP repeat) domains. Some of the IAPs also possess a RING (really interesting new gene) domain with E3 ubiquitin ligase activity. In this issue of the Biochemical Journal, Blankenship et al. unveil the presence of an UBA (ubiquitin-associated domain) in several IAPs. UBAs in c-IAPs (cellular IAPs) bind to monoubiquitin and ubiquitin chains and are implicated in degradation of c-IAPs by promoting their interaction with proteasomes as well as in regulation of TNF-alpha (tumour necrosis factor-alpha)-induced apoptosis. These novel observations establish IAPs as ubiquitin-interacting proteins and opens up new lines of investigation. PMID:19061481

Rajalingam, Krishnaraj; Dikic, Ivan

2009-01-01

183

DNA Damage Response and Apoptosis  

PubMed Central

A number of methods have been developed to examine the morphologic, biochemical, and molecular changes that happen during the DNA damage response that may ultimately lead to death of cells through various mechanisms that include apoptosis. When cells are exposed to ionizing radiation or chemical DNA-damaging agents, double-stranded DNA breaks (DSB) are generated that rapidly result in the phosphorylation of histone variant H2AX. Because phosphorylation of H2AX at Ser 139 correlates well with each DSB, phospho-H2AX is a sensitive marker to used to examine the DNA damage and its repair. Apoptotic cells are characterized on the basis of their reduced DNA content and morphologic changes, including nuclear condensation, which can be detected by flow cytometry (sub-G1 DNA content), trypan blue, or Hoechst staining. The appearance of phosphatidylserine on the plasma membrane with annexin V–fluorochrome conjugates indicates the changes in plasma membrane composition and function. By combining it with propidium iodide staining, this method can also be used to distinguish early versus late apoptotic or necrotic events. The activation of caspases is another well-known biochemical marker of apoptosis. Finally, the Bcl-2 family of proteins and the mitochondria that play a critical role in DNA damage-induced apoptosis can be examined by translocation of Bax and cytochrome c in and out of mitochondria. In this chapter, we discuss the most commonly used techniques used in our laboratory for determining the DNA damage response leading to apoptosis. PMID:18603118

Plesca, Dragos; Mazumder, Suparna; Almasan, Alexandru

2010-01-01

184

Intervention for apoptosis in cardiomyopathy  

Microsoft Academic Search

Apoptosis plays an important role in pathogenesis of primary and secondary cardiomyopathies. It is proposed that antiapoptotic\\u000a interventions may constitute an effective strategy for these diseases. Some of the antiapoptotic interventions are “old wine\\u000a in a new bottle” measures already included in the conventional pharmacotherapy. As specific antiapoptotic treatment, caspase\\u000a inhibitors and anti-TNF-? antibody are in early phases of clinical

Hiroyuki Yaoita; Yukio Maruyama

2008-01-01

185

APOPTOSIS: Life and Death Decisions  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Screening small molecules for their ability to perturb a cellular pathway, a strategy called forward chemical genetics, can yield unexpected information about other pathway components. This is well illustrated by new work (Jiang et al.), as Nicholson and Thornberry discuss in their Perspective. Discovery of a small-molecule activator of apoptosis implicated a tumor suppressor protein and an oncoprotein in the regulation of the mitochondrial cell death pathway.

Donald W. Nicholson (Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories;); Nancy A. Thornberry (Merck Research Laboratories;)

2003-01-10

186

The ATP Switch in Apoptosis  

Microsoft Academic Search

As a result of the work outlined above and other studies, a clear-cut distinction between apoptosis and necrosis no longer\\u000a exists at the biochemical level. The strongest evidence for overlap comes from studies in models of hypoxia showing that over-expression\\u000a of Bcl2 or its homolog Bcl-xL can block necrosis. The effects of Bcl2 appear largely due to direct effects on

David J. McConkey

187

Mathematical modeling and statistical analysis of SPE-OCDMA systems utilizing second harmonic generation effect in thick crystal receivers  

NASA Astrophysics Data System (ADS)

In this paper we analytically study and evaluate the performance of a Spectral-Phase-Encoded Optical CDMA system for different parameters such as the user's code length and the number of users in the network. In this system an advanced receiver structure in which the Second Harmonic Generation effect imposed in a thick crystal is employed as the nonlinear pre-processor prior to the conventional low speed photodetector. We consider ASE noise of the optical amplifiers, effective in low power conditions, besides the multiple access interference (MAI) noise which is the dominant source of noise in any OCDMA communications system. We use the results of the previous work which we analyzed the statistical behavior of the thick crystals in an optically amplified digital lightwave communication system to evaluate the performance of the SPE-OCDMA system with thick crystals receiver structure. The error probability is evaluated using Saddle-Point approximation and the approximation is verified by Monte-Carlo simulation.

Matinfar, Mehdi D.; Salehi, Jawad A.

2009-11-01

188

Response surface methodology applied to SPE for the determination of ibuprofen in various types of water samples.  

PubMed

Over the last few years, there has been a growing concern about the presence of pharmaceuticals in the environment. The main objective of this study was to develop and validate an SPE method using surface response methodology for the determination of ibuprofen in different types of water samples. The influence of sample pH and sample volume on the ibuprofen recovery was studied. The effect of each studied independent variable is pronounced on the dependent variable (ibuprofen recovery). Good selectivity, extraction efficiency, and precision were achieved using 600 mL of sample volume with the pH adjusted to 2.2. LC with fluorescence detection was employed. The optimized method was applied to 20 water samples from the North and South of Portugal. PMID:23907765

Paíga, Paula; Delerue-Matos, Cristina

2013-10-01

189

spe425-01 page 1 Stein, S., 2007, Approaches to continental intraplate earthquake issues, in Stein, S., and Mazzotti, S., ed., Continental Intraplate Earthquakes: Science, Hazard, and  

E-print Network

spe425-01 page 1 1 Stein, S., 2007, Approaches to continental intraplate earthquake issues, in Stein, S., and Mazzotti, S., ed., Continental Intraplate Earthquakes: Science, Hazard, and Policy Issues. The Geological Society of America Special Paper 425 2007 Approaches to continental intraplate earthquake issues

Stein, Seth

190

Copyright 1999, Society of Petroleum Engineers Inc. This paper was prepared for presentation at the 1999 SPE Asia Pacific Oil and Gas  

E-print Network

to provide guidelines for field development in the Spraberry Trend Area. Introduction Naturally fractured at the 1999 SPE Asia Pacific Oil and Gas Conference and Exhibition held in Jakarta, Indonesia, 20­22 April-3836, U.S.A., fax 01-972- 952-9435. Abstract The Spraberry Trend Area in west Texas presents unusual

Schechter, David S.

191

Copyright 2007, Society of Petroleum Engineers This paper was prepared for presentation at the SPE Europec/EAGE Annual Conference and  

E-print Network

Copyright 2007, Society of Petroleum Engineers This paper was prepared for presentation at the SPE by the Society of Petroleum Engineers and are subject to correction by the author(s). The material, as presented, does not necessarily reflect any position of the Society of Petroleum Engineers, its officers

192

Copyright 2000, Society of Petroleum Engineers Inc. This paper was prepared for presentation at the 2000 SPE Eastern Regional Meeting held in  

E-print Network

the paper was presented. Write Librarian, SPE, P.O. Box 833836, Richardson, TX 75083-3836, U.S.A., fax 01-972-952-9435. Abstract Magnetic resonance logs provide the capability of in-situ measurement of reservoir characteristics such as effective porosity, fluid saturation, and rock permeability. This study presents a new and novel methodology

Mohaghegh, Shahab

193

Copyright 2004, Society of Petroleum Engineers, Inc. This paper was prepared for presentation at the SPE Formation Damage Conference held in  

E-print Network

history have seen that water resources dictate the development of civilizations.1, 2 Historically, oneSPE 86526 Copyright 2004, Society of Petroleum Engineers, Inc. This paper was prepared by the Society of Petroleum Engineers and are subject to correction by the author(s). The material, as presented

194

Copyright 2000, Society of Petroleum Engineers Inc. This paper was prepared for presentation at the SPE Asia Pacific Oil and Gas Conference and  

E-print Network

at the SPE Asia Pacific Oil and Gas Conference and Exhibition held in Brisbane, Australia, 16­18 October 2000 in the Spraberry Trend Area in west Texas, USA. The results demonstrate that CO2 gravity drainage could A CO2 pilot is now being conducted in the E.T. O'Daniel Unit of the naturally fractured Spraberry Trend

Schechter, David S.

195

Inflammatory cytokine expression on the ocular surface in the Botulium toxin B induced murine dry eye model  

PubMed Central

Purpose Inflammation plays an important role in dry eye syndrome. In this study, inflammatory cytokine expression on the ocular surface in the Botulium toxin B (BTX-B) induced mouse dry eye model was investigated. Methods CBA/J mice received an injection of saline or 20 milliunits (mU) of BTX-B into the lacrimal gland. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at 3 time points after. The pro-inflammatory cytokines macrophage inhibitory factor (MIF), interleukin-1? (IL-1 ?), tumor necrosis factor-? (TNF- ?) and interleukin-6 (IL-6) in conjunctival and corneal epithelium were evaluated by real time quantitative PCR and immunohistochemistry. Results BTX-B injected mice showed significantly decreased aqueous tear production and increased corneal fluorescein staining at the 1 week and 2 week time points compared with normal control and saline-injected mice. The BTX-B injected mice mRNA expression levels of TNF-? and IL-1? from conjunctival and corneal epithelial cells increased significantly at two early time points comparing with that of normal and saline injected mice, but IL-1? returned to normal levels at the 4 week time point. Saline injected mice showed no difference in mRNA expression of TNF-?, IL-1?, MIF, and IL-6 on the ocular surface tissue at all time points. Immunohistochemistry confirmed these findings. Conclusions BTX-B induced mouse model showed decreased aqueous tear production, increased corneal fluorescein staining, and TNF-? and IL-1? increased expression on the ocular surface within one month. The patterns seen appeared to mimic those in humans with non-Sjögren’s syndrome keratoconjunctivitis sicca (NS-KCS). PMID:19190733

Zhu, Lei; Shen, Jikui; Zhang, Cheng; Park, Choul Yong; Kohanim, Sahar; Yew, Margaret; Parker, John S.

2009-01-01

196

AMPK activator, AICAR, inhibits palmitate-induced apoptosis in osteoblast  

Microsoft Academic Search

Osteoblast apoptosis reduces bone mineral density. Apoptosis can be induced in a variety of cells by palmitate, which is one of the most common saturated fatty acids in dietary fat. The AMPK activator, AICAR, has been shown to inhibit palmitate-induced apoptosis. However, the role of palmitate in osteoblast apoptosis is currently unknown. This study examined whether palmitate could induce apoptosis

Ji-Eun Kim; Myun-Whan Ahn; Suk-Hwan Baek; In Kyu Lee; Yong-Woon Kim; Jong-Yeon Kim; Jin-Myoung Dan; So-Young Park

2008-01-01

197

Apoptosis in Lung Injury and Disease  

Microsoft Academic Search

Pulmonary cell death may contribute significantly to acute and chronic lung injuries caused by various adverse environmental\\u000a agents. Pulmonary cells may die by necrosis, apoptosis, and other forms of regulated cell death. Apoptosis exerts a homeostatic\\u000a function in lung defense and development, through the removal of dysfunctional cells and by regulating cellular proliferation.\\u000a Lung cell apoptosis can occur as a

Stefan W. Ryter; Hong Pyo Kim; Augustine M. K. Choi

198

Pre-Shot Simulations of Far-Field Ground Motions for the Source Physics Experiment (SPE) Explosions at the Climax Stock, Nevada National Security Site  

SciTech Connect

The Source Physics Experiment (SPE) will involve a series of explosions in various geologic and emplacement conditions to validate numerical simulation methods to predict behavior of seismic wave excitation and propagation for nuclear test monitoring. The first SPE's currently underway involve explosions in the Climax Stock (granitic geology) at the Nevada National Security Site (NNSS). Detailed geologic data and published material properties for the major lithologic units of the NNSS and surrounding region were used to build three-dimensional models for seismic wave propagation simulations. The geologic structure near the SPE shot point is quite varied including granitic, carbonate, tuff and alluvium lithologies. We performed preliminary ground motion simulations for a near-source domain covering 8 km x 8 km at the surface centered on the shot point to investigate various source and propagation effects using WPP, LLNL's anelastic seismic wave finite difference code. Simulations indicate that variations in wave propagation properties of the sub-surface will generate strongly path-dependent response once the energy has left the relatively small granitic geology of the near-surface Climax Stock near the SPE shot point. Rough topography to the north and west of SPE shot point causes additional complexity in the signals including energy on the transverse components. Waves propagate much faster through the granitic and carbonate formations and slower through the tuff and alluvium. Synthetic seismograms for a pure explosion source in a 3D geologic structure show large amplitudes on transverse component. For paths to the south sampling the granite, tuff and alluvium lithologies transverse component amplitudes are as high as 50% of that on the vertical and radial components.

Rodgers, A J; Wagoner, J; Petersson, N A; Sjogreen, B

2010-11-07

199

Puromycin aminonucleoside induces glomerular epithelial cell apoptosis.  

PubMed

Glomerular epithelial cell (GEC) injury has been considered to play an important role in puromycin aminonucleoside (PAN)-induced nephrosis. We studied the effect of PAN on rat as well as human GEC apoptosis. Morphogic evaluation of GEC apoptosis and necrosis was carried out by staining with H-33342 and propidium iodide. GEC apoptosis was further confirmed by DNA fragmentation assay (by both agarose gel electrophoresis and end-labeling). To determine the dose- and time-response effect of PAN, GECs were treated with variable concentrations of PAN (10 to 500 microg/ml) for variable time periods (6 to 48 h). To determine the role of gene synthesis, we studied the effect of actinomycin D (a transcriptional inhibitor) on PAN-induced GEC apoptosis. To determine the role of free radicals, we evaluated the effect of superoxide dismutase (SOD), dimethylthiourea (DMTU), and catalase on PAN-induced GEC apoptosis. PAN induced GEC apoptosis in a dose- and time-dependent manner. PAN at a high concentration (PAN, 100 microg/ml) also induced a moderate degree of GEC necrosis. In DNA fragmentation assays PAN-treated GECs showed the classic ladder pattern. PAN-induced GEC apoptosis was partly attenuated with free radical scavengers, such as SOD, DMTU, and catalase. In addition, actinomycin D attenuated PAN-induced GEC apoptosis. PAN induces GEC apoptosis, which may be mediated through the generation of reactive oxygen species. PMID:11170791

Sanwal, V; Pandya, M; Bhaskaran, M; Franki, N; Reddy, K; Ding, G; Kapasi, A; Valderrama, E; Singhal, P C

2001-02-01

200

Apoptosis and Molecular Targeting Therapy in Cancer  

PubMed Central

Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

2014-01-01

201

Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro  

PubMed Central

Aim: Retigeric acid B (RAB), a pentacyclic triterpenic acid from Lobaria kurokawae Yoshim, has been found to induce apoptosis in prostate cancer cells. The aim of this study was to investigate the roles of mitochondrial damage-caused mitophagy in RAB-induced prostate cancer cell death in vitro. Methods: Human prostate cancer PC3 and LNCaP cells were tested. Cell viability was analyzed with MTT assay. Cell apoptosis, ROS level and mitochondrial transmembrane potential (mt??) were measured with flow cytometry. Autophagy- and apoptosis-related proteins were studied using Western blotting. GFP-LC3B puncta, mitochondrial swelling and mitophagy were examined morphologically. Quantitative RT-PCR was used to measure LC3B mRNA level, and siRNA was used to knock down LC3BII. Results: In both PC3 and LNCaP cells, RAB (15 ?mol/L) increased ROS accumulation and decreased mt?? in a time-dependent manner. Furthermore, RAB induced mitochondrial swelling and mitophagy, significantly increased LC3B expression and conversion of LC3BI to LC3BII, and the elimination of mitochondria by LC3BII-containing autophagolysosomes. In addition, RAB suppressed the PI3K/Akt/mTOR pathway activation. Pretreatment of PC3 cells with autophagy inhibitor 3-MA (5 mmol/L) or the lysosomal protease inhibitor CQ (10 ?mol/L) significantly increased RAB-induced apoptosis. Similar results were obtained in RAB-treated PC3 cells with LC3B knocked down. Conclusion: RAB induces mitochondrial damage and mitophagy that attenuates RAB-induced prostate cancer cell death. Thus, suppression of mitophagy might be a potential strategy for improving the chemotherapeutic effects of RAB. PMID:23892275

Liu, Yong-qing; Ji, Yuan; Li, Xian-zhe; Tian, Ke-li; Yf Young, Charles; Lou, Hong-xiang; Yuan, Hui-qing

2013-01-01

202

Apoptosis Inducing, Conformationally Constrained, Dimeric Peptide Analogs of KLA with Submicromolar Cell Penetrating Abilities.  

PubMed

The apoptosis inducing KLA peptide, (KLAKLAK)2, possesses an ability to disrupt mitochondrial membranes. However, this peptide has a poor eukaryotic cell penetrating potential and, as a result, it requires the assistance of other cell penetrating peptides for effective translocation in micromolar concentrations. In an effort to improve the cell penetrating potential of KLA, we have created a library in which pairs of residues on its hydrophobic face are replaced by Cys. The double Cys mutants were then transformed to bundle dimers by oxidatively generating two intermolecular disulfide bonds. We envisioned that once transported into cells, the disulfide bonds would undergo reductive cleavage to generate the monomeric peptides. The results of these studies showed that one of the mutant peptides, dimer B, has a high cell penetrating ability that corresponds to 100% of fluorescence positive cells at 250 nM. Even though dimer B induces disruption of the mitochondrial potential and cytochrome c release followed by caspase activation at submicromolar concentrations, it displays an LD50 of 1.6 ?M under serum conditions using HeLa cells. Taken together, the results demonstrate that the strategy involving formation of bundle dimeric peptides is viable for the design of apoptosis inducing KLA peptide that translocate into cells at submicromolar concentrations. PMID:25188534

Hyun, Soonsil; Lee, Seonju; Kim, Seoyeon; Jang, Sangmok; Yu, Jaehoon; Lee, Yan

2014-10-13

203

APOPTOSIS: Death by Crowd Control  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Cells often die by way of a controlled suicide called apoptosis. The proteins most responsible for the deed are caspases, specific proteases that are carefully regulated in the cell so that they only become activated when absolutely necessary. In his Perspective, Hengartner discusss results reported by Yang et al. in the same issue on how some of the central caspases responsible for cell death, such as CED-3, are activated by oligomerization, a process that is regulated by the anti-death protein CED-9, a member of the large Bcl-2 family.

Michael Hengartner (Cold Spring Harbor Laboratory;)

1998-08-28

204

The Source Physics Experiments (SPE): A Physics-Based Approach to Discriminate Low-Yield Nuclear Events (Invited)  

NASA Astrophysics Data System (ADS)

Discriminating low-yield nuclear explosions is one of the current challenges in the field of monitoring and verification. Work is currently underway in Nevada to address this challenge by conducting a series of experiments using a physics-based approach. This has been accomplished by using a multifaceted, multi-disciplinary approach that includes a range of activities, from characterizing the shallow subsurface to acquiring new explosion data both in the near field (< 100 m from the source) to the far field (> 100 m to 10 s km from the source). The Source Physics Experiment (SPE) is a collaborative project between National Security Technologies, LLC, Lawrence Livermore National Laboratory, Los Alamos National Laboratory, Sandia National Laboratories, the Defense Threat Reduction Agency, and the Air Force Technical Applications Center. The goal of the SPE is to understand the transition of seismic energy from the near field to the far field; to understand the development of S-waves in explosives sources; and to understand how anisotropy controls seismic energy transmission and partitioning. To fully explore these problems, the SPE test series includes tests in both simple and complex geology cases. The current series is being conducted in a highly fractured granite body. This location was chosen, in part, because it was the location of previous nuclear tests in the same rock body and because generally the geology has been well characterized. In addition to historic data, high-resolution seismic reflection, cross-hole tomography, core samples, LIDAR, hyperspectral, and fracture mapping data have been acquired to further characterize and detect changes after each of the shot across the test bed. The complex geology series includes 7 planned shots using conventional explosives in the same shot hole surrounded by Continuous Reflectometry for Radius vs. Time Experiment (CORRTEX), Time of Arrival, Velocity of Detonation, down-hole accelerometers, surface accelerometers, infrasound, and a suite of seismic sensors of various frequency bands from the near field to the far field. This allows for the use of a single test bed in the granite instead of multiple test beds to obtain the same results. The shots are planned at various depths to obtain a Green's function, scaled depth-of-burial data, nominal depth-of-burial data and damage-zone data. Three shots have been executed to date and the fourth is planned for August 2013 as a 220 lb (100 kg) TNT equivalent shot at a depth of 315 ft (96 m). Over 400 data channels have been recorded on the first series of shots with high fidelity. Once the complex geology site data have been exploited, a new test bed will be developed in a simpler geology to test these physics-based models. Ultimately, the results from this project will provide the next advances in the science of monitoring to enable a physics-based predicative capability. This work was done by National Security Technologies, LLC, under Contract No. DE-AC52-06NA25946 with the U.S. Department of Energy. DOE/NV/25946--1835.

Snelson, C. M.; Chipman, V.; White, R. L.; Emmitt, R.; Townsend, M.

2013-12-01

205

Apoptosis: A Review of Programmed Cell Death  

PubMed Central

The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis. PMID:17562483

Elmore, Susan

2007-01-01

206

THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY.  

EPA Science Inventory

The role of apoptosis in neurodegeneration in developing animals and in adults has become increasingly apparent in the past ten years. Normal apoptosis occurs in the CNS from the embryonic stage through senescence, with different cells in each region of the nervous system having ...

207

Flagellin delays spontaneous human neutrophil apoptosis  

Microsoft Academic Search

Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella

Gabriela V Salamone; Yanina Petracca; Juan I Fuxman Bass; Martín Rumbo; Karen A Nahmod; Maria L Gabelloni; Mónica E Vermeulen; Mario J Matteo; Jorge R Geffner; Analia S Trevani

2010-01-01

208

Detection of apoptosis in tissue sections  

Microsoft Academic Search

During the last few years, detection of apoptosis has evolved from a predominantly morphological basis to the use of ever more specific techniques. The methods widely used to visualize DNA fragmentation in tissue sections are now supplemented by a variety of specific antisera against components of the cell death pathways. Essential requirements for apoptosis detection techniques include high sensitivity for

Christine Stadelmann; Hans Lassmann

2000-01-01

209

CELL BIOLOGY: Apoptosis--the Calcium Connection  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Calcium ions are crucial to many cellular processes including apoptosis. In their Perspective, Demaurex and Distelhorst explain new work that shows how calcium ions flowing between the endoplasmic reticulum (ER) and mitochondria regulate programmed cell death, highlighting the ER as a new gateway to apoptosis (Scorrano et al.).

Nicolas Demaurex (University of Geneva Medical Center;Department of Physiology); Clark Distelhorst (Case Western Reserve University Medical School;Department of Medicine)

2003-04-04

210

Apoptosis inducers in chronic lymphocytic leukemia  

PubMed Central

Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis and is still an incurable disease. Numerous apoptosis inducers have been described. These synthetic compounds and natural products (mainly derived from plants) display antileukemic properties in vitro and in vivo and some have even been tested in the clinic in CLL. They act through several different mechanisms. Most of them involve proteins of the Bcl-2 family, which are the key regulators in triggering the mitochondrial pathway of caspase-dependent apoptosis. Thus, the Mcl-1/Noxa axis appeared as a target. Here I overview natural and synthetic apoptosis inducers and their mechanisms of action in CLL cells. Opportunities for developing novel, apoptosis-based therapeutics are presented. PMID:24525395

Billard, Christian

2014-01-01

211

Destruxin B Isolated from Entomopathogenic Fungus Metarhizium anisopliae Induces Apoptosis via a Bcl-2 Family-Dependent Mitochondrial Pathway in Human Nonsmall Cell Lung Cancer Cells  

PubMed Central

Destruxin B, isolated from entomopathogenic fungus Metarhizium anisopliae, is one of the cyclodepsipeptides with insecticidal and anticancer activities. In this study, destruxin B was extracted and purified by ion-exchange chromatography, silica gel chromatography, and semipreparative high-performance liquid chromatography. The potential anticancer effects and molecular mechanisms of destruxin B in human nonsmall cell lung cancer cell lines were characterized. Our results showed that destruxin B induced apoptotic cell death in A549 cells. This event was accompanied by the activation of caspase-2, -3, and -9. Moreover, destruxin B increased the expression level of proapoptotic molecule, PUMA, while decreased antiapoptotic molecule Mcl-1. Additionally, the translocation of Bax from cytosol to mitochondrial membrane was observed upon destruxin B treatment. Knockdown of Bax by shRNA effectively attenuated destruxin-B-triggered apoptosis in A549 cells. Interestingly, similar toxic effects and underlying mechanisms including caspase activation, upregulation of PUMA, and downregulation of Mcl-1 were also observed in a p53-null lung cancer H1299 cell line upon destruxin B treatment. Taken together, our findings suggest that destruxin-B-induced apoptosis in human nonsmall cell lung cancer cells is via a Bcl-2 family-dependent mitochondrial pathway. PMID:24204395

Wu, Chun-Chi; Chen, Tzu-Hsiu; Liu, Bing-Lan; Wu, Li-Chen; Chen, Yung-Ching; Tzeng, Yew-Min; Hsu, Shih-Lan

2013-01-01

212

Nitric Oxide Functions as a Signal in Ultraviolet-B-Induced Baicalin Accumulation in Scutellaria baicalensis Suspension Cultures  

PubMed Central

Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, N?-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation. PMID:24646913

Zhang, Jin-Jie; Li, Xue-Qin; Sun, Jun-Wei; Jin, Song-Heng

2014-01-01

213

Interaction of COP1 and UVR8 regulates UV-B-induced photomorphogenesis and stress acclimation in Arabidopsis  

PubMed Central

The ultraviolet-B (UV-B) portion of the solar radiation functions as an environmental signal for which plants have evolved specific and sensitive UV-B perception systems. The UV-B-specific UV RESPONSE LOCUS 8 (UVR8) and the multifunctional E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) are key regulators of the UV-B response. We show here that uvr8-null mutants are deficient in UV-B-induced photomorphogenesis and hypersensitive to UV-B stress, whereas overexpression of UVR8 results in enhanced UV-B photomorphogenesis, acclimation and tolerance to UV-B stress. By using sun simulators, we provide evidence at the physiological level that UV-B acclimation mediated by the UV-B-specific photoregulatory pathway is indeed required for survival in sunlight. At the molecular level, we demonstrate that the wild type but not the mutant UVR8 and COP1 proteins directly interact in a UV-B-dependent, rapid manner in planta. These data collectively suggest that UV-B-specific interaction of COP1 and UVR8 in the nucleus is a very early step in signalling and responsible for the plant's coordinated response to UV-B ensuring UV-B acclimation and protection in the natural environment. PMID:19165148

Favory, Jean-Jacques; Stec, Agnieszka; Gruber, Henriette; Rizzini, Luca; Oravecz, Attila; Funk, Markus; Albert, Andreas; Cloix, Catherine; Jenkins, Gareth I; Oakeley, Edward J; Seidlitz, Harald K; Nagy, Ferenc; Ulm, Roman

2009-01-01

214

Interaction of COP1 and UVR8 regulates UV-B-induced photomorphogenesis and stress acclimation in Arabidopsis.  

PubMed

The ultraviolet-B (UV-B) portion of the solar radiation functions as an environmental signal for which plants have evolved specific and sensitive UV-B perception systems. The UV-B-specific UV RESPONSE LOCUS 8 (UVR8) and the multifunctional E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) are key regulators of the UV-B response. We show here that uvr8-null mutants are deficient in UV-B-induced photomorphogenesis and hypersensitive to UV-B stress, whereas overexpression of UVR8 results in enhanced UV-B photomorphogenesis, acclimation and tolerance to UV-B stress. By using sun simulators, we provide evidence at the physiological level that UV-B acclimation mediated by the UV-B-specific photoregulatory pathway is indeed required for survival in sunlight. At the molecular level, we demonstrate that the wild type but not the mutant UVR8 and COP1 proteins directly interact in a UV-B-dependent, rapid manner in planta. These data collectively suggest that UV-B-specific interaction of COP1 and UVR8 in the nucleus is a very early step in signalling and responsible for the plant's coordinated response to UV-B ensuring UV-B acclimation and protection in the natural environment. PMID:19165148

Favory, Jean-Jacques; Stec, Agnieszka; Gruber, Henriette; Rizzini, Luca; Oravecz, Attila; Funk, Markus; Albert, Andreas; Cloix, Catherine; Jenkins, Gareth I; Oakeley, Edward J; Seidlitz, Harald K; Nagy, Ferenc; Ulm, Roman

2009-03-01

215

Nitric oxide functions as a signal in ultraviolet-B-induced baicalin accumulation in Scutellaria baicalensis suspension cultures.  

PubMed

Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, N?-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation. PMID:24646913

Zhang, Jin-Jie; Li, Xue-Qin; Sun, Jun-Wei; Jin, Song-Heng

2014-01-01

216

NF-?B-inducing kinase is a key regulator of inflammation-induced and tumour-associated angiogenesis.  

PubMed

Angiogenesis is essential during development and in pathological conditions such as chronic inflammation and cancer progression. Inhibition of angiogenesis by targeting vascular endothelial growth factor (VEGF) blocks disease progression, but most patients eventually develop resistance which may result from compensatory signalling pathways. In endothelial cells (ECs), expression of the pro-angiogenic chemokine CXCL12 is regulated by non-canonical nuclear factor (NF)-?B signalling. Here, we report that NF-?B-inducing kinase (NIK) and subsequent non-canonical NF-?B signalling regulate both inflammation-induced and tumour-associated angiogenesis. NIK is highly expressed in endothelial cells (ECs) in tumour tissues and inflamed rheumatoid arthritis synovial tissue. Furthermore, non-canonical NF-?B signalling in human microvascular ECs significantly enhanced vascular tube formation, which was completely blocked by siRNA targeting NIK. Interestingly, Nik(-/-) mice exhibited normal angiogenesis during development and unaltered TNF?- or VEGF-induced angiogenic responses, whereas angiogenesis induced by non-canonical NF-?B stimuli was significantly reduced. In addition, angiogenesis in experimental arthritis and a murine tumour model was severely impaired in these mice. These studies provide evidence for a role of non-canonical NF-?B signalling in pathological angiogenesis, and identify NIK as a potential therapeutic target in chronic inflammatory diseases and tumour neoangiogenesis. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25043127

Noort, Ae R; van Zoest, Katinka Pm; Weijers, Ester M; Koolwijk, Pieter; Maracle, Chrissta X; Novack, Deborah V; Siemerink, Martin J; Schlingemann, Reinier O; Tak, Paul P; Tas, Sander W

2014-11-01

217

Novel inhibitors are cytotoxic for myeloma cells with NFkB inducing kinase-dependent activation of NFkB  

PubMed Central

NFkB activity is critical for survival and proliferation of normal lymphoid cells and many kinds of B-cell tumors, including multiple myeloma (MM). NFkB activating mutations, which are apparent progression events, enable MM tumors to become less dependent on bone marrow signals that activate NFkB. Mutations that activate NFkB-inducing kinase (NIK) protein are the most prevalent among the many kinds of NFkB mutations in MM tumors. NIK is the main activating kinase of the alternative NFkB pathway, although over-expression of NIK also can activate the classical pathway. Two NIK inhibitors and an isomeric control were tested with human myeloma cell lines. These specific NIK inhibitors are selectively cytotoxic for cells with NIK-dependent activation of NFkB. Combination therapy targeting NIK and IKKbeta (as a main kinase of the classical NFkB pathway) represents a promising treatment strategy in MM. NIK inhibitors can also be useful tool for assessing the role of NIK and alternative NFkB pathway in different cells. PMID:24980832

Demchenko, Yulia N.; Brents, Leslie A.; Li, Zhihong; Bergsagel, Leif P.; McGee, Lawrence R.; Kuehl, Michael W.

2014-01-01

218

Determination of etoxazole residues in fruits and vegetables by SPE clean-up and HPLC-DAD.  

PubMed

A method for determination of etoxazole residues in apples, strawberries and green beans was developed and validated. The analyte was extracted with acetonitrile from foodstuff and a charcoal-celite cartridge was used for clean-up of raw extracts. Reversed phase high performance liquid chromatography with photodiode array detector (HPLC-DAD) was used for the determination and quantification of etoxazole residues in the studied samples. The calibration graphs of etoxazole in a solvent or three blank matrixes were linear within the tested intervals 0.01-2 mg L(-1), with correlation coefficient of determination >0.999. The combined solid phase extraction (SPE) clean-up and the chromatographic method steps were sensitive and reliable for simultaneous determination of etoxazole residues in the studied samples. The average recoveries of etoxazole in the tested foodstuffs were between 93.4 to 102% at spiking levels of 0.01, 0.10, and 0.50 mg kg(-1), with relative standard deviations ranging from 2.8 to 4.7%, in agreement with directives for method validation in residue analyses. The limit of detection (LOD) of the HPLC-DAD system was 100 pg. The limit of quantification of the entire method was 0.01 mg kg(-1). PMID:23431971

Malhat, Farag; Badawy, Hany; Barakat, Dalia; Saber, Ayman

2013-01-01

219

Ionic-liquid-functionalized magnetic particles as an adsorbent for the magnetic SPE of sulfonylurea herbicides in environmental water samples.  

PubMed

In this paper, a new ionic-liquid-functionalized magnetic material was prepared based on the immobilization of an ionic liquid on silica magnetic particles that could be successfully used as an adsorbent for the magnetic SPE of five sulfonylurea herbicides (bensulfuron-methyl, prosulfuron, pyrazosulfuron-ethyl, chlorimuron-ethyl and triflusulfuron-methyl) from environmental water samples. The main parameters affecting the extraction efficiency such as desorption conditions, sample pH, extraction time and so on, were optimized using the Taguchi method. Good linearities were obtained with correlation coefficients ranging from 0.9992 to 0.9999 in the concentration range of 0.1-50 ?g L(-1) and the LODs were 0.053-0.091 ?g L(-1). Under the optimum conditions, the enrichment factors of the method were 1155-1380 and the recoveries ranged from 77.8 to 104.4%. The proposed method was reliable and could be applied to the residue analysis of sulfonylurea herbicides in environmental water samples (tap, reservoir and river). PMID:23894051

He, Zeying; Liu, Donghui; Zhou, Zhiqiang; Wang, Peng

2013-10-01

220

A ?-SPE procedure for the determination of cannabinoids and their metabolites in urine by LC-MS/MS.  

PubMed

In this paper the development and validation of a method for the analysis of THC-COOH, THC, THC-OH, CBD and CBN in their total form in urine by LC-MS/MS is presented. Tandem hydrolysis, i.e. enzymatic and basic, has been found optimal for the simultaneous analysis of the selected analytes in urine: basic hydrolysis is more effective for the cleavage of THC-COOH glucuronide while enzymatic hydrolysis allows the cleavage of the conjugated cannabinoids possessing ether bonds (THC, THC-OH, CBD). The whole procedure requires a 2h enzymatic hydrolysis using only 90?L of urine by ?-SPE extraction technique with C18 tips. Clear advantages in terms of time and of enzyme reduction are obtained and the cost of the analysis can be dramatically reduced. Satisfactory recovery values and matrix effect are obtained, and the chromatographic run, performed with a fused-core column, allowed the complete analyte separation in only 3min (total run 5.8min) with a common HPLC system. Furthermore the whole procedure has been validated according to SWGTOX guidelines: LOQs are between 6 and 10ppb, quite lower than the requested cut-off for urine testing; intermediate reproducibility of the selected analytes is below 10% and accuracy is between 85% and 113%, except for CBD, included only for semi-quantitative determination. PMID:24469020

Montesano, Camilla; Sergi, Manuel; Odoardi, Sara; Simeoni, Maria Chiara; Compagnone, Dario; Curini, Roberta

2014-03-01

221

Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.  

PubMed

The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information. PMID:23818305

Silva, Lorena M A; Filho, Elenilson G A; Thomasi, Sérgio S; Silva, Bianca F; Ferreira, Antonio G; Venâncio, Tiago

2013-09-01

222

Proneurotrophins, Seizures, and Neuronal Apoptosis  

PubMed Central

Neurons respond to numerous factors in their environment that influence their survival and function during development and in the mature brain. Among these factors, the neurotrophins have been shown to support neuronal survival and function, acting primarily through the Trk family of receptor tyrosine kinases. However, recent studies have established that the uncleaved neurotrophin precursors, the proneurotrophins, can be secreted and induce apoptosis via the p75 neurotrophin receptor, suggesting that the balance of secreted mature and proneurotrophins has a critical impact on neuronal survival or death. Epileptic seizures elicit increases in both proneurotrophin secretion and p75NTR expression, shifting the balance of these factors toward signaling cell death. This review will discuss the evidence that this ligand-receptor system plays an important role in neuronal loss following seizures. PMID:20360602

Friedman, Wilma J.

2010-01-01

223

APOPTOSIS: Death of a Monopoly?  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Hunot and Flavell discuss recent findings in Nature by Joza et al. that point to the existence of a new sort of cell death. Cell death is required during the development of an organism to remove portions of the body that will not be needed; this cell death usually requires destructive enzymes called caspases to perform the final demolition of the cell. But cavitation, an early developmental process in the mouse embryo that requires cell death, has now been suggested to occur through a caspase-independent pathway that instead uses a mitochondrial protein called AIF (apoptosis-inducing factor).

Stéphane Hunot (Yale University School of Medicine;Section of Immunobiology and the Howard Hughes Medical Institute); Richard A. Flavell (Yale University School of Medicine;Section of Immunobiology and the Howard Hughes Medical Institute)

2001-05-04

224

A Novel Staphylococcal Cassette Chromosomal Element, SCCfusC, Carrying fusC and speG in Fusidic Acid-Resistant Methicillin-Resistant Staphylococcus aureus  

PubMed Central

A high prevalence of fusC (16/46, 59%) was found in fusidic acid-resistant methicillin-resistant Staphylococcus aureus isolates collected from 2008 to 2010. Nucleotide sequencing of fusC and flanking regions revealed a novel staphylococcal cassette chromosome (SCC) structure, SCCfusC, which was integrated into rlmH and located upstream from SCCmec. The SCCfusC element contained speG, which may contribute to the polyamine resistance. PMID:24277045

Lin, Yu-Tzu; Tsai, Jui-Chang; Chen, Hsiao-Jan; Hung, Wei-Chun; Hsueh, Po-Ren

2014-01-01

225

Analysis of Carbaryl and Carbofuran in Drinking Water with Post-Column Derivatization Using Agilent's New LC Column and SampliQ SPE Cartridges  

Microsoft Academic Search

The herbicides carbaryl and carbofuran were analyzed in drinking water samples using Agilent's new reversed-phase columns, Agilent TC-C18(2), and Agilent's new line of SampliQ C18 SPE cartridges. To meet the requirements of EPA Method 531.1 (1), we tried a 400-µL direct injection onto the new column. Even with such a large injection volume, the new column provided good resolution from

Rongjie Fu

226

Analysis of anti-inflammatory, analgesic, stimulant and antidepressant drugs in purified water from wastewater treatment plants using SPE-LC tandem mass spectrometry  

Microsoft Academic Search

This work presents an effective sample preparation method for the evaluation of seven pharmaceutical compounds belonging to different therapeutic classes in purified water from wastewater treatment plants (WWTPs). The target compounds include caffeine (stimulant), nicotine (stimulant), atenolol (beta blocker), metamizole (anti-inflammatory and analgesic), fluoxetine (antidepressant), paraxanthine (stimulant) and clofibric acid (lipid regulator). Solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS)

Cristina Afonso-Olivares; Zoraida Sosa-Ferrera; José J. Santana-Rodríguez

2012-01-01

227

Use of an automated on-line SPE-HPLC method to monitor caffeine and selected aniline and phenol compounds in aquatic systems of Macedonia-Thrace, Greece  

Microsoft Academic Search

Caffeine and selected aniline and phenol compounds have been monitored in the river, lake, and ground water of Northern Greece (Macedonia-Thrace) from September 1999 to December 2000 by means of a fully automated on-line SPE-HPLC method. Among the target aniline and phenol compounds the most abundant was 2,6-di-tert-butyl-4-methylphenol, which was found to be present in both surface and ground water

E. Papadopoulou-Mourkidou; J. Patsias; E. Papadakis; A. Koukourikou

2001-01-01

228

Simultaneous Determination of Nine Water and Fat Soluble Vitamins After SPE Separation and RP-HPLC Analysis in Pharmaceutical Preparations and Biological Fluids  

Microsoft Academic Search

An automated reversed phase high performance liquid-chromatography (RP-HPLC) method is described, for the simultaneous analysis of water soluble [ascorbic acid (C), nicotinic acid, nicotinamide, folic acid, cyanocobalamine (B12), and riboflavin (B2)] and fat soluble (retinol, ?-tocopherol, ?-tocopherol acetate) vitamins. The compounds are separated after solid-phase extraction (SPE) on C18 cartridges, where water soluble vitamins pass unretained, while fat soluble vitamins

I. N. Papadoyannis; G. K. Tsioni; V. F. Samanidou

1997-01-01

229

Bulk segregant analysis followed by high-throughput sequencing reveals the Neurospora cell cycle gene, ndc-1, to be allelic with the gene for ornithine decarboxylase, spe-1.  

PubMed

With the advent of high-throughput DNA sequencing, it is now straightforward and inexpensive to generate high-density small nucleotide polymorphism (SNP) maps. Here we combined high-throughput sequencing with bulk segregant analysis to expedite mutation mapping. The general map location of a mutation can be identified by a single backcross to a strain enriched in SNPs compared to a standard wild-type strain. Bulk segregant analysis simultaneously increases the likelihood of determining the precise nature of the mutation. We present here a high-density SNP map between Neurospora crassa Mauriceville-1-c (FGSC2225) and OR74A (FGSC2489), the strains most typically used by Neurospora researchers to carry out mapping crosses. We further have demonstrated the utility of the Mauriceville sequence and our approach by mapping the mutation responsible for the only existing temperature-sensitive (ts) cell cycle mutation in Neurospora, nuclear division cycle-1 (ndc-1). The single T-to-C point mutation maps to the gene encoding ornithine decarboxylase (ODC), spe-1 (NCU01271), and changes a Phe to a Ser residue within a highly conserved motif next to the catalytic site of the enzyme. By growth on spermidine and complementation with a wild-type spe-1 gene, we showed that the defect in spe-1 is responsible for the ts ndc-1 mutation. Based on our results, we propose changing ndc-1 to spe-1(ndc), which reflects that this mutation results in an ODC with a specific nuclear division defect. PMID:21515825

Pomraning, Kyle R; Smith, Kristina M; Freitag, Michael

2011-06-01

230

Manumycin induces apoptosis in prostate cancer cells  

PubMed Central

Background Manumycin exhibits an antitumor effect in a variety of cancer cell lines, including prostate cancer cell lines (DU145 and PC-3). Our previous studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the current study, we further evaluated the effect of manumycin in two prostate cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying mechanisms. Materials and methods The cell viability of prostate cancer cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. The expressions of B-cell lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3 were detected by Western blotting. Results Manumycin treatment resulted in significant decreases in the viabilities of the two prostate cancer cell lines in a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9 activation. A specific inhibitor of caspase-9 protected cells from caspase-3 activation, apoptosis, and cytotoxicity induced by manumycin. We also found that manumycin downregulated Bcl-2 expression and upregulated Bax expression. Conclusion Our data suggest that manumycin induces apoptosis in prostate cancer cells through regulation of the Bcl-2 family involving caspase-9 activation. These results suggest that manumycin may be beneficial for the treatment of prostate cancer. PMID:24899815

Li, Jing-Gao; She, Miao-Rong; Lu, Ci-Yong; Wei, Shan-Shan; Xia, Ping-Fang; Lu, Ze-Sheng; Peng, Qi

2014-01-01

231

Apoptosis induced by bovine ephemeral fever virus.  

PubMed

The potential significance of bovine ephemeral fever virus (BEFV)-induced apoptosis and involved viral molecules was fully unknown. In the present study, evidence is provided demonstrating that bovine ephemeral fever virus induces apoptosis in several cell lines. Five types of assays for apoptosis were used in examining BEFV-infected cells. (1) Assay for DNA fragmentation, (2) nuclear staining with acridine orange, (3) ELISA detection of cytoplasmic histone-associated DNA fragment, (4) terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay of BEFV-infected cells, (5) observation of blebbing of the plasma membrane and the formation of apoptotic bodies of apoptic cells by scanning electron microscope. The level of lactate dehydrogenase (LDH) in BEFV-infected cells was increased significantly after 20-25 h post-infection. Caspases-2, -3, -4, -6, -8, -9, and -10 were activated in BEFV-infected BHK-21 cells. To determine further whether BEFV-induced apoptosis was caspase-dependent, the effect of the tripeptide pan-ICE (caspase) inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyketone on the inhibition of apoptosis in BEFV-infected BHK-21 cells, was investigated. Apoptosis could be blocked by the caspase inhibitor (Z-VAD-fmk), indicating that BEFV induces caspase-dependent apoptosis in cultured cells. PMID:15542140

Chang, Chia J; Shih, Wen L; Yu, Feng L; Liao, Ming H; Liu, Hung J

2004-12-15

232

An in-line SPE strategy to enhance sensitivity in CE for the determination of pharmaceutical compounds in river water samples.  

PubMed

In this study, the suitability of solid-phase extraction (SPE) coupled in-line to CE with UV-Vis detection was evaluated for the preconcentration and separation of diluted solutions of five pharmaceuticals compounds: benzafibrate, piroxicam, diclofenac sodium, naproxen and clofibric acid. An SPE analyte concentrator containing Oasis(®) HLB sorbent was constructed without frits and placed near the inlet end of the separation capillary. Different parameters such as sample pH, composition and volume of the elution plug and sample loading time were studied in order to obtain the maximum preconcentration factors. The LODs reached for standard samples were in the range 0.06-0.5?ng/mL with good reproducibility, and the developed strategy provides sensitivity enhancement factors around 14,000-fold in peak area and 5900-fold in peak height compared with the normal hydrodynamic injection. Finally, river water samples fortified with the pharmaceutical compounds were analyzed by the developed in-line SPE-CE-UV method in order to show the potential of the methodology for the analysis of environmental aquatic samples. For these samples, high values of relative recoveries, between 73-107% and 79-103% for two concentration levels, 5 and 25?ng/mL, respectively, were obtained and LODs ranged between 0.19 and 1?ng/mL. PMID:21769895

Maijó, Irene; Borrull, Francesc; Calull, Marta; Aguilar, Carme

2011-08-01

233

Application of Colorimetric Solid Phase Extraction (C-SPE) to Monitoring Nickel(II) and Lead(II) in Spacecraft Water Supplies  

NASA Technical Reports Server (NTRS)

Archived water samples collected on the International Space Station (ISS) and returned to Earth for analysis have, in a few instances, contained trace levels of heavy metals. Building on our previous advances using Colorimetric Solid Phase Extraction (C-SPE) as a biocide monitoring technique, we are devising methods for the low level monitoring of nickel(II), lead(II) and other heavy metals. C-SPE is a sorption-spectrophotometric platform based on the extraction of analytes onto a membrane impregnated with a colorimetric reagent that are then quantified on the surface of the membrane using a diffuse reflectance spectrophotometer. Along these lines, we have determined nickel(II) via complexation with dimethylglyoxime (DMG) and begun to examine the analysis of lead(II) by its reaction with 2,5- dimercapto-1,3,4-thiadiazole (DMTD) and 4-(2- pyridylazo)-resorcinol (PAR). These developments are also extending a new variant of C-SPE in which immobilized reagents are being incorporated into this methodology in order to optimize sample reaction conditions and to introduce the colorimetric reagent. This paper describes the status of our development of these two new methods.

Diaz, Neil C.; Gazda, Daniel B.; Fritz, James S.; Porter, Marc D.; Rutz, Jeff; Mudgett, Paul; Schultz, John

2004-01-01

234

Apoptosis: programmed cell death in fetal development.  

PubMed

Controlled death of cells is as much a part of embryonal development as is cell proliferation and differentiation. This cell suicide is controlled by cell genes involved in induction or prevention of programmed cell death (PCD). During embryogenesis PCD implicates cell elimination, necessary in fashioning of the body, moulding of tissues. PCD is often used synonymous with the designation apoptosis, which indicates an endogenous cell suicide program by which useless or crippled cells are eliminated. Apoptosis occurs in normal tissue turnover, in organ involution after withdrawal of trophic hormones, in distinct cells after deprivation of growth factors or specific stimuli and in cells which have undergone sublethal damage. During PCD the nucleus breaks up into DNA fragments of 180-200 kD and the endoplasmic reticulum transforms into vesicles, which are released as apoptotic bodies into the extracellular space. The apoptotic bodies, containing cell organelles and nuclear fragments, are phagocytosed by neighboring cells. Electron micrographs of embryos have revealed the presence of numerous cells with the characteristic features of apoptosis. Experiments, in which small tissue fragments were explanted to other regions, have proven that focal apoptosis is under control of genetic, hormonal and local tissue factors. Morphological analysis has shown that most of the ovarian follicles undergo during development apoptosis, resulting in follicle atresia. Only a small proportion escapes PCD. Growth factors and estrogens have been identified as follicle survival factors, androgens and gonadotropin releasing hormones are potentiating apoptosis of the follicle. An exaggerated PCD or a defective apoptosis during embryogenesis may cause developmental abnormalities. Certain viruses can inhibit apoptosis, while metabolic stress or damage of cell structures can induce apoptosis. Therefore not only viral infections, also drugs and chemical or physical injuries during embryogenesis may interfere with the balanced PCD and thus induce malformations. Drugs and therapy designs directed to modulate the apoptotic process will offer new approaches to the prevention of congenital malformations. PMID:8801138

Haanen, C; Vermes, I

1996-01-01

235

Modeling heterogeneous responsiveness of intrinsic apoptosis pathway  

PubMed Central

Background Apoptosis is a cell suicide mechanism that enables multicellular organisms to maintain homeostasis and to eliminate individual cells that threaten the organism’s survival. Dependent on the type of stimulus, apoptosis can be propagated by extrinsic pathway or intrinsic pathway. The comprehensive understanding of the molecular mechanism of apoptotic signaling allows for development of mathematical models, aiming to elucidate dynamical and systems properties of apoptotic signaling networks. There have been extensive efforts in modeling deterministic apoptosis network accounting for average behavior of a population of cells. Cellular networks, however, are inherently stochastic and significant cell-to-cell variability in apoptosis response has been observed at single cell level. Results To address the inevitable randomness in the intrinsic apoptosis mechanism, we develop a theoretical and computational modeling framework of intrinsic apoptosis pathway at single-cell level, accounting for both deterministic and stochastic behavior. Our deterministic model, adapted from the well-accepted Fussenegger model, shows that an additional positive feedback between the executioner caspase and the initiator caspase plays a fundamental role in yielding the desired property of bistability. We then examine the impact of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise, and natural variation of protein concentrations, viewed as extrinsic noise, on behavior of the intrinsic apoptosis network. Histograms of the steady-state output at varying input levels show that the intrinsic noise could elicit a wider region of bistability over that of the deterministic model. However, the system stochasticity due to intrinsic fluctuations, such as the noise of steady-state response and the randomness of response delay, shows that the intrinsic noise in general is insufficient to produce significant cell-to-cell variations at physiologically relevant level of molecular numbers. Furthermore, the extrinsic noise represented by random variations of two key apoptotic proteins, namely Cytochrome C and inhibitor of apoptosis proteins (IAP), is modeled separately or in combination with intrinsic noise. The resultant stochasticity in the timing of intrinsic apoptosis response shows that the fluctuating protein variations can induce cell-to-cell stochastic variability at a quantitative level agreeing with experiments. Finally, simulations illustrate that the mean abundance of fluctuating IAP protein is positively correlated with the degree of cellular stochasticity of the intrinsic apoptosis pathway. Conclusions Our theoretical and computational study shows that the pronounced non-genetic heterogeneity in intrinsic apoptosis responses among individual cells plausibly arises from extrinsic rather than intrinsic origin of fluctuations. In addition, it predicts that the IAP protein could serve as a potential therapeutic target for suppression of the cell-to-cell variation in the intrinsic apoptosis responsiveness. PMID:23875784

2013-01-01

236

Apoptosis in Cardiovascular Remodeling—Effect of Medication  

Microsoft Academic Search

In the last decade, apoptosis has emerged as a key determinant of target organ damage in cardiovascular diseases. The suggestion that increased cardiomyocyte apoptosis participates in the etiology of heart failure probably contributed to the negative view of the prevalence of apoptosis in the field of cardiovascular diseases. However, we and others have shown that up-regulation of apoptosis in certain

Denis deBlois; Sergei N. Orlov; Pavel Hamet

2001-01-01

237

Courses: Nursing (NURS) Page 355Sonoma State University 2011-2012 Catalog nurS 312 bACCAlAureAte nurSinG perSpeCtiVeS i (4)  

E-print Network

Courses: Nursing (NURS) Page 355Sonoma State University 2011-2012 Catalog nurS 312 bACCAlAureAte nurSinG perSpeCtiVeS i (4) Explore contemporary perspectives in baccalaureate nursing with emphasis, leadership and professional development. nurS 313 bACCAlAureAte nurSinG perSpeCtiVeS ii (4) Seminar, 4 hours

Ravikumar, B.

238

Pentoxifylline and other protein kinase C inhibitors down-regulate HIV-LTR NF-kappa B induced gene expression.  

PubMed Central

BACKGROUND: This investigation deals with the molecular mechanism of anti-human immunodeficiency virus type 1 (HIV-1) action of pentoxifylline (PTX) [1-(5'-oxohexyl)-3, 7-dimethylxanthine] a drug widely used for the treatment of conditions involving defective regional microcirculation. MATERIALS AND METHODS: The inhibition by PTX of protein kinase C (PKC) or cAMP-dependent protein kinase (PKA)-mediated activation by phorbol ester (PMA) and tumor necrosis factor alpha (TNF-alpha) of HIV-1-LTR-regulated reporter gene expression was studied in human CD4+ T lymphocytes (Jurkat) and human embryo kidney cells (293-27-2). A protein kinase C is involved in activation of NF-kappa B in whole cells, identified by using inhibitors specific for PKC- or PKA-catalyzed NF-kappa B activation in whole cell and cell-free systems. RESULTS: PTX inhibited PKC- or PKA-catalyzed activation of NF-kappa B in cytoplasmic extracts from unstimulated Jurkat or 293-27-2 cells, but not interaction of preactivated NF-kappa B with its motifs. Calphostin C, a specific inhibitor of PKC, inhibited NF-kappa B activation and HIV-1 LTR-driven reporter gene expression in both PMA- and TNF-alpha-treated cells. In contrast, although H88 specifically inhibited PKA activity in the cell-free extract, it did not affect NF-kappa B action in PMA- or TNF-alpha-treated cells. CONCLUSIONS: The mechanism of inhibitory action of PTX on virus replication and NF-kappa B-induced transactivation of HIV-1 gene expression has been elucidated as due to blocking PKC-dependent PMA- or TNF-alpha-induced activation of NF-kappa B in Jurkat and 293-27-2 cells. Other protein kinase inhibitors may be useful in down regulating transcription of HIV-1 provirus and thereby virus replication in HIV-infected patients. Images FIG. 1 FIG. 2 FIG. 6 PMID:8790599

Biswas, D. K.; Ahlers, C. M.; Dezube, B. J.; Pardee, A. B.

1994-01-01

239

DDM1 and ROS1 have a role in UV-B induced- and oxidative DNA damage in A. thaliana  

PubMed Central

Absorption of UV-B by DNA induces the formation of covalent bonds between adjacent pyrimidines. In maize and arabidopsis, plants deficient in chromatin remodeling show increased DNA damage compared to WT plants after a UV-B treatment. However, the role of enzymes that participate in DNA methylation in DNA repair after UV-B damage was not previously investigated. In this work, we analyzed how chromatin remodeling activities that have an effect on DNA methylation affects the repair of UV-B damaged DNA using plants deficient in the expression of DDM1 and ROS1. First, we analyzed their regulation by UV-B radiation in arabidopsis plants. Then, we demonstrated that ddm1 mutants accumulated more DNA damage after UV-B exposure compared to Col0 plants. Surprisingly, ros1 mutants show less CPDs and 6-4PPs than WT plants after the treatment under light conditions, while the repair under dark conditions is impaired. Transcripts for two photolyases are highly induced by UV-B in ros1 mutants, suggesting that the lower accumulation of photoproducts by UV-B is due to increased photorepair in these mutants. Finally, we demonstrate that oxidative DNA damage does not occur after UV-B exposure in arabidopsis plants; however, ros1 plants accumulate high levels of oxoproducts, while ddm1 mutants have less oxoproducts than Col0 plants, suggesting that both ROS1 and DDM1 have a role in the repair of oxidative DNA damage. Together, our data provide evidence that both DDM1 and ROS1, directly or indirectly, participate in UV-B induced- and oxidative DNA damage repair. PMID:24155752

Questa, Julia I.; Fina, Julieta P.; Casati, Paula

2013-01-01

240

Apoptosis in the developing human heart resembles apoptosis in epithelial tissues  

Microsoft Academic Search

It is widely accepted that apoptosis plays an important role in the development of the heart as well as in different heart\\u000a diseases. Despite extensive research efforts, many issues regarding apoptosis in the heart remain unsolved, including the\\u000a detection of apoptotic cardiomyocytes, their morphological features, the mechanisms of their removal and the clinical significance\\u000a of apoptosis in the heart. It

Maja Jerše; Nina Zidar

2011-01-01

241

Dispersal of Group A Streptococcal Biofilms by the Cysteine Protease SpeB Leads to Increased Disease Severity in a Murine Model  

PubMed Central

Group A Streptococcus (GAS) is a Gram-positive human pathogen best known for causing pharyngeal and mild skin infections. However, in the 1980's there was an increase in severe GAS infections including cellulitis and deeper tissue infections like necrotizing fasciitis. Particularly striking about this elevation in the incidence of severe disease was that those most often affected were previously healthy individuals. Several groups have shown that changes in gene content or regulation, as with proteases, may contribute to severe disease; yet strains harboring these proteases continue to cause mild disease as well. We and others have shown that group A streptococci (MGAS5005) reside within biofilms both in vitro and in vivo. That is to say that the organism colonizes a host surface and forms a 3-dimensional community encased in a protective matrix of extracellular protein, DNA and polysaccharide(s). However, the mechanism of assembly or dispersal of these structures is unclear, as is the relationship of these structures to disease outcome. Recently we reported that allelic replacement of the streptococcal regulator srv resulted in constitutive production of the streptococcal cysteine protease SpeB. We further showed that the constitutive production of SpeB significantly decreased MGAS5005?srv biofilm formation in vitro. Here we show that mice infected with MGAS5005?srv had significantly larger lesion development than wild-type infected animals. Histopathology, Gram-staining and immunofluorescence link the increased lesion development with lack of disease containment, lack of biofilm formation, and readily detectable levels of SpeB in the tissue. Treatment of MGAS5005?srv infected lesions with a chemical inhibitor of SpeB significantly reduced lesion formation and disease spread to wild-type levels. Furthermore, inactivation of speB in the MGAS5005?srv background reduced lesion formation to wild-type levels. Taken together, these data suggest a mechanism by which GAS disease may transition from mild to severe through the Srv mediated dispersal of GAS biofilms. PMID:21547075

Connolly, Kristie L.; Roberts, Amity L.; Holder, Robert C.; Reid, Sean D.

2011-01-01

242

SPE HG-AAS method for the determination of inorganic arsenic in rice--results from method validation studies and a survey on rice products.  

PubMed

The present paper describes the development, validation and application of a method for inorganic arsenic (iAs) determination in rice samples. The separation of iAs from organoarsenic compounds was done by off-line solid-phase extraction (SPE) followed by hydride generation atomic absorption spectrometry (HG-AAS) detection. This approach was earlier developed for seafood samples (Rasmussen et al., Anal Bioanal Chem 403:2825-2834, 2012) and has in the present work been tailored for rice products and further optimised for a higher sample throughput and a lower detection limit. Water bath heating (90 °C, 60 min) of samples with dilute HNO3 and H2O2 solubilised and oxidised all iAs to arsenate (As(V)). Loading of buffered sample extracts (pH 6?±?1) followed by selective elution of arsenate from a strong anion exchange SPE cartridge enabled the selective iAs quantification by HG-AAS, measuring total arsenic (As) in the SPE eluate. The in-house validation gave mean recoveries of 101-106% for spiked rice samples and in two reference samples. The limit of detection was 0.02 mg kg(-1), and repeatability and intra-laboratory reproducibility were less than 6 and 9%, respectively. The SPE HG-AAS method produced similar results compared to parallel high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (ICP-MS) analysis. The SPE separation step was tested collaboratively, where the laboratories (N?=?10) used either HG-AAS or ICP-MS for iAs determination in a wholemeal rice powder. The trial gave satisfactory results (HorRat value of 1.6) and did not reveal significant difference (t test, p?>?0.05) between HG-AAS and ICP-MS quantification. The iAs concentration in 36 rice samples purchased on the Danish retail market varied (0.03-0.60 mg kg(-1)), with the highest concentration found in a red rice sample. PMID:23604416

Rasmussen, Rie R; Qian, Yiting; Sloth, Jens J

2013-09-01

243

Alternative calibration techniques for counteracting the matrix effects in GC-MS-SPE pesticide residue analysis - A statistical approach.  

PubMed

This paper investigates the efficiency of application of four different multivariate calibration techniques, namely matrix-matched internal standard (MMIS), matrix-matched external standard (MMES), solvent-only internal standard (SOIS) and solvent-only external standard (SOES) on the detection and quantification of 20 organochlorine compounds from high, low and blank matrix water sample matrices by Gas Chromatography-Mass Spectrometry (GC-MS) coupled to solid phase extraction (SPE). Further statistical testing, using Statistical Package for the Social Science (SPSS) by applying MANOVA, T-tests and Levene's F tests indicates that matrix composition has a more significant effect on the efficiency of the analytical method than the calibration method of choice. Matrix effects are widely described as one of the major sources of errors in GC-MS multiresidue analysis. Descriptive and inferential statistics proved that the matrix-matched internal standard calibration was the best approach to use for samples of varying matrix composition as it produced the most precise average mean recovery of 87% across all matrices tested. The use of an internal standard calibration overall produced more precise total recoveries than external standard calibration, with mean values of 77% and 64% respectively. The internal standard calibration technique produced a particularly high overall standard deviation of 38% at 95% confidence level indicating that it is less robust than the external standard calibration method which had an overall standard error of 32% at 95% confidence level. Overall, the matrix-matched external standard calibration proved to be the best calibration approach for analysis of low matrix samples which consisted of the real sample matrix as it had the most precise recovery of 98% compared to other calibration approaches for the low-matrix samples. PMID:24968235

Rimayi, Cornelius; Odusanya, David; Mtunzi, Fanyana; Tsoka, Shepherd

2015-01-01

244

Advantages of online SPE coupled with UPLC/MS/MS for determining the fate of pesticides and pharmaceutical compounds.  

PubMed

Laboratory experimentation is essential for our understanding of the fate and behaviour of pollutants. Many analytical techniques exist, but they all have disadvantages either in terms of sensitivity or of selectivity. The number of samples that can be analysed, the low volume of samples available during the experiment and the need to identify different degradates are all obstacles that new techniques are able to overcome. The work presented here summarizes progress in the field of metrology as concerns online solid phase extraction technology coupled with liquid chromatography followed by tandem mass spectrometry detection. Recently developed analytical techniques were validated for both 18 pesticides and their degradates and 17 pharmaceuticals and their degradates. Limits of quantification from 20 to 70 ng L(-1) for pharmaceuticals and from 15 to 25 ng L(-1) for pesticides and metabolites have been obtained, with linearity range up to 1 ?g L(-1). The limits of quantification of a few nanograms per litre, the possibility of working on less than 1 mL of sample and the simultaneous quantification of the target products and their transformation products are all advantages that are demonstrated by two environmental applications. The first application concerns the evaluation of ecotoxicological effects of pesticides on aquatic organisms exposed in mesocosms. The second application aims to determine the adsorption constants of pharmaceutical molecules on soils and river sediments. For both applications, the robustness, range of linearity and limit of quantification of the developed analytical methods satisfy the requirements for laboratory experiments conducted under controlled conditions. Specific constraints generated by this type of experiment (adding CaCl2 for the adsorption study and filtration of the water coming from the mesocosms) were not found to limit the use of online SPE. These two preliminary studies show that new experimental fields are possible thanks to online solid phase extraction coupled with liquid chromatography. PMID:23907687

Togola, Anne; Baran, Nicole; Coureau, Charlotte

2014-02-01

245

[Apoptosis and thymocyte development (epithelial cells as inducers of thymocyte apoptosis)].  

PubMed

Apoptosis, together with proliferation, is a main factor of selection of the clones of developing T-lymphocytes: the clones not supported by positive selection are subject to apoptosis and apoptosis accounts for discarding of potentially autoaggressive clones, i.e., for negative selection in the thymus and peripheral lymphoid tissue. Realization of apoptosis at different stages of the development of T-lymphocytes depends to a varying extent on Fas, Bcl-2, p53, and other regulators. The dendritic cells are the main cell type, the contact with determines apoptosis of T-lymphocytes. A possible role of the epithelial cells was shown in few models (on murine cells) and was not practically studied. We obtained a line of epithelial cells of the human thymus cells HTSC, cocultivation with which induces apoptosis of immature thymocytes and blood T-cells activated by mitogens. Development of apoptosis is suppressed by inhibitors of protein and RNA synthesis, chelators Ca2+, ions Zn2+, and factors destroying the cytoskeleton components. In this model, interaction of pairs of molecules CD4-HLA class II and LFA-1-ICAM-1. When in contact with the HTSC cells, the thymocytes of mice mutant for Fas-receptor (line MRL.lpr) are subject to apoptosis, but when this receptor is present, it affects the development of apoptosis. PMID:9609947

Iarilin, A A; Bulanova, E G; Sharova, N I; Budagian, V M

1998-01-01

246

Apoptosis: A Way to Maintain Healthy Individuals  

Microsoft Academic Search

\\u000a Apoptosis, the best known form of programmed cell death, is tightly regulated by a number of sensors, signal transducers and\\u000a effectors. Apoptosis is mainly active during embryonic development, when deletion of redundant cellular material is required\\u000a for the correct morphogenesis of tissues and organs; moreover, it is essential for the maintenance of tissue homeostasis during\\u000a cell life. Cells also activate

Chiara Mondello; A. Ivana Scovassi

247

Apoptosis regulators as targets for cancer therapy  

Microsoft Academic Search

Apoptosis serves to remove excess or damaged cells and its dysregulation may lead to a number of pathological disorders including\\u000a cancer. Studies during the last 20 years have unravelled much of the molecular mechanisms that control apoptosis. Whether\\u000a a cell dies in response to diverse apoptotic stimuli, including DNA-damaging agents, is determined largely by interactions\\u000a between proteins of the Bcl-2

J. L. Fernández-Luna

2007-01-01

248

Apoptosis in Leukemias: Regulation and Therapeutic Targeting  

Microsoft Academic Search

\\u000a Nearly 25 years after the seminal publication of John Foxton Kerr that first described apoptosis, the process of regulated\\u000a cell death, our understanding of this basic physiological phenomenon is far from complete [39]. From cardiovascular disease\\u000a to cancer, apoptosis has assumed a central role with broad ranging therapeutic implications that depend on a complete understanding\\u000a of the molecular events involved

Ismael Samudio; Marina Konopleva; Bing Carter; Michael Andreeff

249

APOPTOSIS: A Cinderella Caspase Takes Center Stage  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. It has been thought that permeabilization of mitochondria and release of cytochrome c is an early event in apoptosis that is required for activation of caspases, the enzyme executioners of the apoptotic cascade. However, in a Perspective, Kumar and Vaux explain new findings (Lassus et al.) that implicate an often ignored caspase, caspase-2, in the early stages of apoptosis prior to mitochondrial permeabilization.

Sharad Kumar (Hanson Institute;); David L. Vaux (Walter and Eliza Hall Institute;)

2002-08-23

250

The domains of apoptosis: a genomics perspective.  

PubMed

Apoptosis plays important roles in many facets of normal physiology in animal species, including programmed cell death associated with fetal development or metamorphosis, tissue homeostasis, immune cell education, and some aspects of aging. Defects in the regulation of apoptosis contribute to multiple diseases associated with either inappropriate cell loss or pathological cell accumulation. Host-pathogen interactions have additionally provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses. To a large extent, the apoptosis machinery can be viewed as a network, with different nodes connected by physical interactions of evolutionarily conserved domains. These domains can serve as signatures for identification of proteins involved in the network. In particular, the caspase recruitment domains (CARDs); death effector domains (DEDs); death domains (DDs); BIR (baculovirus IAP repeat) domains of inhibitor of apoptosis proteins (IAPs); Bcl-2 family proteins; caspase protease domains; and endonuclease-associated CIDE (cell death-inducing DFF45-like effector) domains are found in common in proteins involved in apoptosis. In the genomes of mammals, genes encoding proteins that carry one or more of these signature domains are often present in multiple copies, making up diverse gene families that permit tissue-specific and highly regulated control of cell life and death decisions through combinations of stimulus-specific gene expression and complex protein interaction networks. In this Review, we organize the repertoire of apoptosis proteins of humans into domain families, drawing comparisons with homologs in other vertebrate and invertebrate animal species, and discuss some of the functional implications of these findings. PMID:15226512

Reed, John C; Doctor, Kutbuddin S; Godzik, Adam

2004-06-29

251

Apoptosis in Cancer Biology and Cancer Therapeutics  

Microsoft Academic Search

Most anticancer therapies commonly used in the treatment of human cancer, e.g., chemotherapy, ?-irradiation, immunotherapy,\\u000a or suicide gene therapy, kill tumor cells by triggering cell death pathways including apoptosis in cancer cells. Hence, the\\u000a failure to activate such pathways may lead to the resistance of cancers to current treatment approaches. A better understanding\\u000a of the molecular events that regulate apoptosis

Simone Fulda

252

Cadmium-Induced Apoptosis in Mouse Liver  

Microsoft Academic Search

Apoptosis is a process of active cell death, distinct from necrosis and characterized by specific morphological and biochemical features. Although the acute hepatotoxic effects of cadmium (Cd) are well described, little is known about the occurrence of apoptosis in Cd toxicity. Therefore, mice were injected with 5–60 ?mol\\/kg ip of Cd and their livers were removed 1.5–48 h later and

Sultan S. M. Habeebu; Jie Liu; Curtis D. Klaassen

1998-01-01

253

UV induced bystander signaling leading to apoptosis.  

PubMed

Human keratinocytes (HaCaT) were exposed to UV (A+B) (UVA-350-400 mJ/cm2 and UVB-30 mJ/cm2) which induces apoptosis as evidenced by MTT assay, DNA laddering, Bax and Fas up-regulation. UV induced apoptotic conditioned media (6 h or earlier) did not cause apoptosis in unexposed cells. However, treatment with conditioned medium collected post UV exposure (1 h) induced Bax in unexposed cells as observed by RT-PCR. The induction of cell death was initiated by conditioned medium collected 12 h after UV exposure and the extent of death was increased progressively when conditioned medium collected 24 or 72 h post UV exposure was used. Medium collected 24 h after UV exposure also increased mitochondrial membrane permeability as determined by rhodamine uptake. Conditioned medium induced apoptosis did not involve reactive oxygen species (ROS) unlike UV induced apoptosis indicating that the apoptosis pathway could be different. Interestingly, at high dilution apototic conditioned medium did not induce apoptosis but actually protected cells from UV insult. The role of nerve growth factor (NGF) in UV induced bystander effects are also discussed. PMID:15896462

Banerjee, Gautam; Gupta, Nishma; Kapoor, Arun; Raman, Govindarajan

2005-06-01

254

Hypergastrinemia increases gastric epithelial susceptibility to apoptosis.  

PubMed

Plasma concentrations of the hormone gastrin are elevated by Helicobacter pylori infection and by gastric atrophy. It has previously been proposed that gastrin acts as a cofactor during gastric carcinogenesis and hypergastrinemic transgenic INS-GAS mice are prone to developing gastric adenocarcinoma, particularly following H. pylori infection. We hypothesised that the increased risk of carcinogenesis in these animals may partly result from altered susceptibility of gastric epithelial cells to undergo apoptosis. Gastric corpus apoptosis was significantly increased 48 h after 12Gy gamma-radiation in mice rendered hypergastrinemic by transgenic (INS-GAS) or pharmacological (omeprazole treatment of FVB/N mice) methods and in both cases the effects were inhibited by the CCK-2 receptor antagonist YM022. However, no alteration in susceptibility to gamma-radiation-induced gastric epithelial apoptosis was observed in mice overexpressing progastrin or glycine-extended gastrin. Apoptosis was also significantly increased in gastric corpus biopsies obtained from H. pylori-infected humans with moderate degrees of hypergastrinemia. We conclude that hypergastrinemia specifically renders cells within the gastric corpus epithelium more susceptible to induction of apoptosis by radiation or H. pylori. Altered susceptibility to apoptosis may therefore be one factor predisposing to gastric carcinogenesis in INS-GAS mice and similar mechanisms may also be involved in humans. PMID:17900712

Przemeck, S M C; Varro, A; Berry, D; Steele, I; Wang, T C; Dockray, G J; Pritchard, D M

2008-02-01

255

The Paracrine Role of Stem Cell Factor\\/c-kit Signaling in the Activation of Human Melanocytes in Ultraviolet-B-Induced Pigmentation  

Microsoft Academic Search

The interaction of stem cell factor with its receptor, c-kit, is well known to be critical to the survival of melanocytes. Little is known about the role(s) of the stem cell factor\\/c-kit interaction in epidermal pigmentation, however. To clarify whether the stem cell factor\\/c-kit signaling has a paracrine role in ultraviolet-B-induced pigmentation, we determined whether the exposure of human keratinocytes,

Akira Hachiya; Akemi Kobayashi; Atsushi Ohuchi; Yoshinori Takema; Genji Imokawa

2001-01-01

256

Inhibition of Macroautophagy Triggers Apoptosis  

PubMed Central

Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or monensin). Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a cytomegalovirus-derived gene) or by caspase inhibition. Under conditions in which the fusion between lysosomes and autophagosomes was inhibited, the formation of autophagic vacuoles was enhanced at a preapoptotic stage, as indicated by accumulation of LC3-II protein, ultrastructural studies, and an increase in the acidic vacuolar compartment. Cells exhibiting a morphology reminiscent of (autophagic) type 2 cell death, however, recovered, and only cells with a disrupted mitochondrial transmembrane potential were beyond the point of no return and inexorably died even under optimal culture conditions. All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways. PMID:15657430

Boya, Patricia; Gonzalez-Polo, Rosa-Ana; Casares, Noelia; Perfettini, Jean-Luc; Dessen, Philippe; Larochette, Nathanael; Metivier, Didier; Meley, Daniel; Souquere, Sylvie; Yoshimori, Tamotsu; Pierron, Gerard; Codogno, Patrice; Kroemer, Guido

2005-01-01

257

VASP Activation via the G?13/RhoA/PKA Pathway Mediates Cucurbitacin-B-Induced Actin Aggregation and Cofilin-Actin Rod Formation  

PubMed Central

Cucurbitacin B (CuB), a potent antineoplastic agent of cucurbitacin triterpenoids, induces rapid disruption of actin cytoskeleton and aberrant cell cycle inhibiting carcinogenesis. However, the underlying molecular mechanism of such anticancer effects remains incompletely understood. In this study, we showed that CuB treatment rapidly induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation (i.e. activation) at the Ser157 residue and generated VASP clumps which were co-localized with amorphous actin aggregates prior to the formation of highly-ordered cofilin-actin rods in melanoma cells. Knockdown of VASP or inhibition of VASP activation using PKA-specific inhibitor H89 suppressed CuB-induced VASP activation, actin aggregation and cofilin-actin rod formation. The VASP activation was mediated by cAMP-independent PKA activation as CuB decreased the levels of cAMP while MDL12330A, an inhibitor of adenylyl cyclase, had weak effect on VASP activation. Knockdown of either G?13 or RhoA not only suppressed VASP activation, but also ameliorated CuB-induced actin aggregation and abrogated cofilin-actin rod formation. Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the G?13/RhoA/PKA/VASP pathway. PMID:24691407

Zhang, Yan-Ting; Xu, Li-Hui; Lu, Qun; Liu, Kun-Peng; Liu, Pei-Yan; Ji, Fang; Liu, Xiao-Ming; Ouyang, Dong-Yun; He, Xian-Hui

2014-01-01

258

Formation of cofilin-actin rods following cucurbitacin-B-induced actin aggregation depends on Slingshot homolog 1-mediated cofilin hyperactivation.  

PubMed

Accumulating evidence indicates that cucurbitacin B (CuB), as well as other cucurbitacins, damages the actin cytoskeleton in a variety of cell types. However, the underlying mechanism of such an effect is not well understood. In this study, we showed that CuB rapidly induced actin aggregation followed by actin rod formation in melanoma cells. Cofilin, a critical regulator of actin dynamics, was dramatically dephosphorylated (i.e., activated) upon CuB treatment. Notably, the activated cofilin subsequently formed rod-like aggregates, which were highly colocalized with actin rods, indicating the formation of cofilin-actin rods. Cofilin knockdown significantly suppressed rod formation but did not prevent actin aggregation. Furthermore, knockdown of the cofilin phosphatase Slingshot homolog 1 (SSH1), but not chronophin (CIN), alleviated CuB-induced cofilin hyperactivation and cofilin-actin rod formation. The activity of Rho kinase and LIM kinase, two upstream regulators of cofilin activation, was downregulated after cofilin hyperactivation. Pretreatment with a thiol-containing reactive oxygen species (ROS) scavenger N-acetyl cysteine, but not other ROS inhibitors without thiol groups, suppressed CuB-induced actin aggregation, cofilin hyperactivation and cofilin-actin rod formation, suggesting that thiol oxidation might be involved in these processes. Taken together, our results demonstrated that CuB-induced formation of cofilin-actin rods was mediated by SSH1-dependent but CIN-independent cofilin hyperactivation. PMID:23695982

Zhang, Yan-Ting; Ouyang, Dong-Yun; Xu, Li-Hui; Zha, Qing-Bing; He, Xian-Hui

2013-10-01

259

VASP activation via the G?13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation.  

PubMed

Cucurbitacin B (CuB), a potent antineoplastic agent of cucurbitacin triterpenoids, induces rapid disruption of actin cytoskeleton and aberrant cell cycle inhibiting carcinogenesis. However, the underlying molecular mechanism of such anticancer effects remains incompletely understood. In this study, we showed that CuB treatment rapidly induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation (i.e. activation) at the Ser157 residue and generated VASP clumps which were co-localized with amorphous actin aggregates prior to the formation of highly-ordered cofilin-actin rods in melanoma cells. Knockdown of VASP or inhibition of VASP activation using PKA-specific inhibitor H89 suppressed CuB-induced VASP activation, actin aggregation and cofilin-actin rod formation. The VASP activation was mediated by cAMP-independent PKA activation as CuB decreased the levels of cAMP while MDL12330A, an inhibitor of adenylyl cyclase, had weak effect on VASP activation. Knockdown of either G?13 or RhoA not only suppressed VASP activation, but also ameliorated CuB-induced actin aggregation and abrogated cofilin-actin rod formation. Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the G?13/RhoA/PKA/VASP pathway. PMID:24691407

Zhang, Yan-Ting; Xu, Li-Hui; Lu, Qun; Liu, Kun-Peng; Liu, Pei-Yan; Ji, Fang; Liu, Xiao-Ming; Ouyang, Dong-Yun; He, Xian-Hui

2014-01-01

260

X-Linked Inhibitor of Apoptosis Regulates Lung Fibroblast Resistance to Fas-Mediated Apoptosis  

PubMed Central

The accumulation of apoptosis-resistant fibroblasts within fibroblastic foci is a characteristic feature of idiopathic pulmonary fibrosis (IPF), but the mechanisms underlying apoptosis resistance remain unclear. A role for the inhibitor of apoptosis (IAP) protein family member X-linked inhibitor of apoptosis (XIAP) has been suggested by prior studies showing that (1) XIAP is localized to fibroblastic foci in IPF tissue and (2) prostaglandin E2 suppresses XIAP expression while increasing fibroblast susceptibility to apoptosis. Based on these observations, we hypothesized that XIAP would be regulated by the profibrotic mediators transforming growth factor (TGF)?-1 and endothelin (ET)-1 and that increased XIAP would contribute to apoptosis resistance in IPF fibroblasts. To address these hypotheses, we examined XIAP expression in normal and IPF fibroblasts at baseline and in normal fibroblasts after treatment with TGF-?1 or ET-1. The role of XIAP in the regulation of fibroblast susceptibility to Fas-mediated apoptosis was examined using functional XIAP antagonists and siRNA silencing. In concordance with prior reports, fibroblasts from IPF lung tissue had increased resistance to apoptosis compared with normal lung fibroblasts. Compared with normal fibroblasts, IPF fibroblasts had significantly but heterogeneously increased basal XIAP expression. Additionally, TGF-?1 and ET-1 induced XIAP protein expression in normal fibroblasts. Inhibition or silencing of XIAP enhanced the sensitivity of lung fibroblasts to Fas-mediated apoptosis without causing apoptosis in the absence of Fas activation. Collectively, these findings support a mechanistic role for XIAP in the apoptosis-resistant phenotype of IPF fibroblasts. PMID:23492187

Ajayi, Iyabode O.; Sisson, Thomas H.; Higgins, Peter D. R.; Booth, Adam J.; Sagana, Rommel L.; Huang, Steven K.; White, Eric S.; King, Jessie E.; Moore, Bethany B.

2013-01-01

261

Inhibition of osteoblast apoptosis by thrombin.  

PubMed

The multifunctional serine protease thrombin has been shown to be a specific agonist for a variety of functional responses of cells including osteoblasts. The current study was conducted to determine if thrombin was capable of inhibiting apoptosis in osteoblasts, and if so, to examine the mechanism by which this occurred. Thrombin (20-100 nM) significantly inhibited apoptosis in serum-starved cultures of the human osteoblast-like Saos-2 cell line and cultures of primary osteoblasts isolated from mouse calvariae, as well as dexamethasone-treated primary mouse osteoblasts. Inhibition of serum deprivation-induced apoptosis was shown to require thrombin's specific proteolytic activity. Primary mouse osteoblasts were found to express two functional thrombin receptors, PAR-1 and PAR-4. Thrombin inhibited serum deprivation-induced apoptosis in osteoblasts isolated from PAR-1 null mice to the same degree as in osteoblasts isolated from wild-type mice. Treatment of serum-deprived osteoblasts, isolated from either PAR-1 null or wild-type mice, with a PAR-4-activating peptide failed to significantly inhibit apoptosis compared to the relevant control. Medium conditioned by thrombin-treated osteoblasts, in which thrombin had been inactivated, was able to inhibit serum deprivation-induced osteoblast apoptosis almost as well as thrombin itself. Blocking protein synthesis, by cycloheximide pretreatment of the conditioning cells, prevented this action. The ability of known osteoblast survival factors, such as transforming growth factor beta1, fibroblast growth factor-2, insulin-like growth factor-II, and interleukin-6, to inhibit serum deprivation-induced osteoblast apoptosis was also tested. None of these factors was able to inhibit serum deprivation-induced osteoblast apoptosis to the same extent as thrombin. The results presented here demonstrate that thrombin treatment of osteoblasts inhibits apoptosis induced either by dexamethasone or by serum deprivation. Furthermore, it does so independently of the known thrombin receptors by bringing about the synthesis and/or secretion of an unknown survival factor or factors, which then act in an autocrine fashion to inhibit apoptosis. PMID:14555279

Pagel, Charles N; de Niese, Michael R; Abraham, Linda A; Chinni, Carla; Song, Shu Jun; Pike, Robert N; Mackie, Eleanor J

2003-10-01

262

Training-induced apoptosis in skeletal muscle.  

PubMed

Apoptosis or programmed cell death is a genetically controlled response of cells to commit suicide and is associated with DNA fragmentation or laddering. The common inducers of apoptosis include Ca2+i and oxygen free radicals/oxidative stress, which are also implicated in the pathogenesis of exercise-induced myopathies. To examine training-induced apoptosis, Thoroughbred horses were subjected to 3 months training programme on a treadmill. At the end of the training programme venous blood samples were taken for a creatine kinase (CK) assay. In addition, muscle biopsy samples were obtained for a membrane lipid peroxidation measurement by malondialdehyde (MDA) assay and for apoptosis detection. Apoptosis was studied by visualising the apoptotic myocytes on the paraffin sections by the modified TUNEL method. DNA laddering was evaluated by subjecting the DNA obtained from the biopsies to 1.5% agarose gel electrophoresis. There was a significant increase (P<0.05) of protein-bound MDA, and a nonsignificant trend (P = 0.14) for the control group to have higher levels of CK compared to the trained group. Under light microscopy, percentage of the TUNEL positive cells was higher (P<0.001) in the training group. This result was corroborated with the findings of DNA fragmentation by gel electrophoresis, which showed higher ladders of DNA band at the same group. In conclusion, these results clearly demonstrate that there is training-induced apoptosis in skeletal muscle. It is probable that apoptosis allows the work/recovery/rebound/supercompensation cycle, when unaccustomed muscle cells activate programmed cell death and are replaced by new and stronger cells, which is the mechanism for training-induced increases in fitness. PMID:12405700

Boffi, F M; Cittar, J; Balskus, G; Muriel, M; Desmaras, E

2002-09-01

263

Inhibition of reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs).  

PubMed

IAPs comprise a family of inhibitors of apoptosis found in viruses and animals. In vivo binding studies demonstrated that both baculovirus and Drosophila IAPs physically interact with an apoptosis-inducing protein of Drosophila, Reaper (RPR), through their baculovirus IAP repeat (BIR) region. Expression of IAPs blocked RPR-induced apoptosis and resulted in the accumulation of RPR in punctate perinuclear locations which coincided with IAP localization. When expressed alone, RPR rapidly disappeared from the cells undergoing RPR-induced apoptosis. Expression of P35, a caspase inhibitor, also blocked RPR-induced apoptosis and delayed RPR decline, but RPR remained cytoplasmic in its location. Mutational analysis of RPR demonstrated that caspases were not directly responsible for RPR disappearance. The physical interaction of IAPs with RPR provides a molecular mechanism for IAP inhibition of RPR's apoptotic activity. PMID:9294184

Vucic, D; Kaiser, W J; Harvey, A J; Miller, L K

1997-09-16

264

Peptaibiomics: an advanced, rapid and selective analysis of peptaibiotics/peptaibols by SPE/LC-ES-MS.  

PubMed

"Proteomics" and "peptidomics" are used as technical terms to define the analysis and study of all proteins and peptides expressed in an organism or tissue. In analogy we propose the name peptaibiomics for the analysis of a group of fungal peptide antibiotics (peptaibiotics) containing the characteristic amino acid Aib (alpha-aminoisobutyric acid). In analogy to the peptidome the complete expression of peptaibiotics by fungal multienzyme complexes should be named the peptaibiome. Peptaibiotics are defined as peptides containing Aib and exerting a variety of bioactivities. They comprise the sub-groups of N-acetylated peptaibols, characterized also by a C-terminal amide-linked 2-amino alcohol, and lipopeptaibols having in place of an acetyl group a lipophilic fatty acid acyl group. Furthermore, lipoaminopeptides are also known with long-chain fatty acid on the N-termini, a lipoamino acid in position three and a strongly basic secondary or tertiary amine form a subgroup of mixed forms which could not be integrated in one of these three previously mentioned groups. Here we present a specific and rapid screening method on the peptaibiome applicable directly onto filamentous fungi cultured in a single Petri dish. The method comprises solid-phase extraction (SPE) of peptaibiotics followed by on-line reversed-phase HPLC coupled to an ion trap electrospray tandem mass spectrometer (ES-MS). The presence of these peptides is indicated by characteristic mass differences of Deltam = 85.1 Da representing Aib-residues which can be observed in the b-series of acylium fragment ions resulting from ES-MS. Partial sequences can be deduced from the data and compared with structures compiled in electronic peptaibol data bases. The judgement is possible whether or not structures are novel, already known or related to known structures. Suitability of the method is demonstrated with the analysis of strains of Trichoderma and its teleomorph Hypocrea. New sequences of peptaibiotics are presented and those being related to established 10- to 18-residue peptaibols trichovirin, trichogin and trichotoxin, which have been described in the literature. PMID:16622603

Krause, C; Kirschbaum, J; Brückner, H

2006-06-01

265

Bamboo charcoal as adsorbent for SPE coupled with monolithic column-HPLC for rapid determination of 16 polycyclic aromatic hydrocarbons in water samples.  

PubMed

The coupling of solid-phase extraction (SPE) using bamboo charcoal (BC) as an adsorbent with a monolithic column-high performance liquid chromatography (MC-HPLC) method was developed for the high-efficiency enrichment and rapid determination of 16 polycyclic aromatic hydrocarbons (PAHs) in water. Key influence factors, such as the type and the volume of the elution solvent, and the flow rate and the volume of the sample loading, were optimized to obtain a high SPE recovery and extraction efficiency. BC as an SPE adsorbent presented a high extraction efficiency due to its large specific surface area and high adsorption capacity; MC as an HPLC column accelerated the separation within 8 min because of its high porosity, fast mass transfer, and low-pressure resistance. The calibration curves for the PAHs extracted were linear in the range of 0.2-15 µg/L, with the correlation coefficients (r(2)) between 0.9970-0.9999. This method attained good precisions (relative standard deviation, RSD) from 3.5 to 10.9% for the standard PAHs I aqueous solutions at 5 µg/L; the method recoveries ranged in 52.6-121.6% for real spiked river water samples with 0.4 and 4 µg/L. The limits of detection (LODs, S/N = 3) of the method were determined from 11 and 87 ng/L. The developed method was demonstrated to be applicable for the rapid and sensitive determination of 16 PAHs in real environmental water samples. PMID:22586244

Ma, Jiping; Li, Mo; Li, Jinhua; Rui, Cuijie; Xin, Yanping; Xue, Qinzhao; Chen, Lingxin

2011-10-01

266

BASP1 Promotes Apoptosis in Diabetic Nephropathy  

PubMed Central

Apoptosis contributes to the development of diabetic nephropathy (DN), but the mechanisms that lead to diabetes-induced cell death are not fully understood. Here, we combined a functional genomics screen for cDNAs that induce apoptosis in vitro with transcriptional profiling of renal biopsies from patients with DN. Twelve of the 138 full-length cDNAs that induced cell death in human embryonic kidney cells matched upregulated mRNA transcripts in tissue from human DN. Confirmatory screens identified induction of BASP1 in tubular cross sections of human DN tissue. In vitro, apoptosis-inducing conditions such as serum deprivation, high concentrations of glucose, and proinflammatory cytokines increased BASP1 mRNA and protein in human tubular epithelial cells. In normal cells, BASP1 localized to the cytoplasm, but in apoptotic cells, it colocalized with actin in the periphery. Overexpression of BASP1 induced cell death with features of apoptosis; conversely, small interfering RNA (siRNA)-mediated knockdown of BASP1 protected tubular cells from apoptosis. Supporting possible involvement of BASP1 in renal disease other than DN, we also observed significant upregulation of renal BASP1 in spontaneously hypertensive rats and a trend toward increased tubulointerstitial BASP1 mRNA in human hypertensive nephropathy. In summary, a combined functional genomics approach identified BASP1 as a proapoptotic factor in DN and possibly also in hypertensive nephropathy. PMID:20110383

Sanchez-Nino, Maria Dolores; Sanz, Ana Belen; Lorz, Corina; Gnirke, Andrea; Rastaldi, Maria Pia; Nair, Viji; Egido, Jesus; Ruiz-Ortega, Marta

2010-01-01

267

Estrogen Regulation of Apoptosis in Osteoblasts  

PubMed Central

Dysregulated apoptosis is a critical failure associated with prominent degenerative diseases including osteoporosis. In bone, estrogen deficiency has been associated with accelerated osteoblast apoptosis and susceptibility to osteoporotic fractures. Hormone therapy continues to be an effective option for preventing osteoporosis and bone fractures. Induction of apoptosis in G-292 human osteoblastic cells by exposure to etoposide or the inflammatory cytokine TNF? promoted acute caspase-3/7 activity and this increased activity was inhibited by pretreatment with estradiol. Etoposide also increased the expression of a battery of apoptosis-promoting genes and this expression was also inhibited by estradiol. Among the apoptotic genes whose expression was inhibited by estradiol was ITPR1, which encodes the type 1 InsP3R. InsP3Rs are intracellular calcium channels and key proapoptotic mediators. Estradiol via estrogen receptor ?1 suppresses ITPR1 gene transcription in G-292 cells. These analyses suggest that an underlying basis of the beneficial activity of estrogens in combating osteoporosis may involve the prevention of apoptosis in osteoblasts and that a key event in this process is the repression of apoptotic gene expression and inhibition of caspase-3/7. PMID:19426747

Bradford, Peter G; Gerace, Ken V; Roland, Renee L; Chrzan, Brian G

2010-01-01

268

Evaluation of Apoptosis in Immunotoxicity Testing  

PubMed Central

Immunotoxicity testing is important in determining the toxic effects of chemical substances, medicinal products, airborne pollutants, cosmetics, medical devices, and food additives. The immune system of the host is a direct target of these toxicants, and the adverse effects include serious health complications such as susceptibility to infections, cancer, allergic reactions, and autoimmune diseases. One way to investigate the harmful effects of different chemicals is to study apoptosis in immune cell populations. Apoptosis is defined as the programmed cell death, and in general, this process helps in development and maintains homeostasis. However, in the case of an insult by a toxicant, apoptosis of the immune cells can lead to immunosuppression resulting in the development of cancer and the inability to fight infections. Apoptosis is characterized by cell shrinkage, nuclear condensation, changes in cell membrane and mitochondria, DNA fragmentation into 200 base oligomers, and protein degradation by caspases. Various methods are employed in order to investigate apoptosis. These methods include direct measurement of apoptotic cells with flow cytometry and in situ labeling, as well as RNA, DNA, and protein assays that are indicative of apoptotic molecules. PMID:19967519

Nagarkatti, Mitzi; Rieder, Sadiye Amcaoglu; Vakharia, Dilip; Nagarkatti, Prakash S.

2014-01-01

269

Sodium nitroprusside induces apoptosis of rabbit chondrocytes  

NASA Astrophysics Data System (ADS)

Osteoarthritis (OA) is characterized by a slowly progressing degradation of the matrix and destruction of articular cartilage. Apoptosis of chondrocyte is accounted for the mechanism of OA. Nitric oxide (NO), as a stimulus, has been shown to induce chondrocyte apoptosis by activating the matrix metalloproteinases (MMPs), increasing the expression of cyclooxygenase 2 (COX-2) and the level of prostaglandin E2 (PGE2), inhibiting the proteoglycan synthesis and type II collagen expression. In this study, sodium nitroprusside (SNP) was administered to be the NO donor to explore the mechanism of NO-induced apoptosis of rabbit chondrocytes obtained from six weeks old New Zealand rabbits. CCK-8 assay revealed the inhibitory effect of SNP on cell viability. We used flow cytometry (FCM) to assess the form of cell death by Annexin-V/propidium iodide (PI) double staining, and evaluate the change of mitochondrial membrane potential (??m). We found that the SNP induced chondrocyte apoptosis in a dose- and time-dependent manner and an observable reduction of ??m. In conclusion, our findings indicate that SNP induces apoptosis of rabbit chondrocytes via a mitochondria-mediated pathway.

Liang, Qian; Wang, Xiao-Ping; Chen, Tong-Sheng

2013-02-01

270

Apoptosis of Beta cells in diabetes mellitus.  

PubMed

Diabetes mellitus is a multifactorial metabolic disorder characterized by hyperglycemia. Apoptosis in beta cells has been observed in response to diverse stimuli, such as glucose, cytokines, free fatty acids, leptin, and sulfonylureas, leading to the activation of polyol, hexosamine, and diacylglycerol/protein kinase-C (DAG/PKC) pathways that mediate oxidative and nitrosative stress causing the release of different cytokines. Cytokines induce the expression of Fas and tumor necrosis factor-alpha (TNF-?) by activating the transcription factor, nuclear factor-?b, and signal transducer and activator of transcription 1 (STAT-1) in the ? cells in the extrinsic pathway of apoptosis. Cytokines produced in beta cells also induce proapoptotic members of the intrinsic pathway of apoptosis. The genetic alterations in apoptosis signaling machinery and the pathogenesis of diabetes include Fas, FasL, Akt, caspases, calpain-10, and phosphatase and tensin homolog (Pten). The other gene products that are involved in diabetes are nitric oxide synthase-2 (NOS2), small ubiquitin-like modifier (SUMO), apolipoprotein CIII (ApoCIII), forkhead box protein O1 (FOXO1), and Kruppel-like zinc finger protein Gli-similar 3 (GLIS3). The gene products having antiapoptotic nature are Bcl-2 and Bcl-XL. Epigenetic mechanisms play an important role in type I and type II diabetes. Further studies on the apoptotic genes and gene products in diabetics may be helpful in pharmacogenomics and individualized treatment along with antioxidants targeting apoptosis in diabetes. PMID:25093391

Anuradha, Rachakatla; Saraswati, Mudigonda; Kumar, Kishore G; Rani, Surekha H

2014-11-01

271

Fully automated trace level determination of parent and alkylated PAHs in environmental waters by online SPE-LC-APPI-MS/MS.  

PubMed

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous compounds that enter the environment from natural and anthropogenic sources, often used as markers to determine the extent, fate, and potential effects on natural resources after a crude oil accidental release. Gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction (LLE+GC-MS) has been extensively used to isolate and quantify both parent and alkylated PAHs. However, it requires labor-intensive extraction and cleanup steps and generates large amounts of toxic solvent waste. Therefore, there is a clear need for greener, faster techniques with enough reproducibility and sensitivity to quantify many PAHs in large numbers of water samples in a short period of time. This study combines online solid-phase extraction followed by liquid chromatography (LC) separation with dopant-assisted atmospheric pressure photoionization (APPI) and tandem MS detection, to provide a one-step protocol that detects PAHs at low nanograms per liter with almost no sample preparation and with a significantly lower consumption of toxic halogenated solvents. Water samples were amended with methanol, fortified with isotopically labeled PAHs, and loaded onto an online SPE column, using a large-volume sample loop with an auxiliary LC pump for sample preconcentration and salt removal. The loaded SPE column was connected to an UPLC pump and analytes were backflushed to a Thermo Hypersil Green PAH analytical column where a 20-min gradient separation was performed at a variable flow rate. Detection was performed by a triple-quadrupole MS equipped with a gas-phase dopant delivery system, using 1.50 mL of chlorobenzene dopant per run. In contrast, LLE+GC-MS typically use 150 mL of organic solvents per sample, and methylene chloride is preferred because of its low boiling point. However, this solvent has a higher environmental persistence than chlorobenzene and is considered a carcinogen. The automated system is capable of performing injection, online SPE, inorganic species removal, LC separation, and MS/MS detection in 28 min. Selective reaction monitoring was used to detect 28 parent PAHs and 15 families of alkylated PAHs. The methodology is comparable to traditional GC-MS and was tested with surface seawater, rainwater runoff, and a wastewater treatment plant effluent. Positive detections above reporting limits are described. The virtual absence of sample preparation could be particularly advantageous for real-time monitoring of discharge events that introduce PAHs into environmental compartments, such as accidental releases of petroleum derivates and other human-related events. This work covers optimization of APPI detection and SPE extraction efficiency, a comparison with LLE+GC-MS in terms of sensitivity and chromatographic resolution, and examples of environmental applications. PMID:24217946

Ramirez, Cesar E; Wang, Chengtao; Gardinali, Piero R

2014-01-01

272

Apoptosis and Cytokines in Nonalcoholic Steatohepatitis  

PubMed Central

Nonalcoholic fatty liver disease (NAFLD) is one of the commonest causes of chronic liver disease in the United States, and represents several overlapping clinicopathological states, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although dysregulated lipid accumulation occurs across the spectrum of NAFLD, features of liver cell injury such as hepatocyte ballooning, cytoskeletal changes (Mallory-Denk bodies) and hepatocyte apoptosis occur predominantly in NASH, and distinguish NASH from simple steatosis. Indeed, NASH is a more serious form of liver damage, as cirrhosis and / or hepatocellular carcinoma are potential outcomes of NASH, but rarely occurs in individuals with simple steatosis. Hepatic injury and apoptosis that occur in adults is often dysregulated and is accompanied by the accumulation of immune cells, which produce cytokines and growth factors that drives chronic inflammation and may result in fibrosis. The purpose of this review is to summarize the process of apoptosis and roles of putative cytokines in progressive NAFLD. PMID:19818305

Syn, Wing-Kin; Choi, Steve S; Diehl, Anna Mae

2009-01-01

273

p38-NF-?B-promoted mitochondria-associated apoptosis and G2/M cell cycle arrest in norcantharidin-treated HeLa cells.  

PubMed

Previous study proved that norcantharidin (NCTD) could exert its anticancer activity in a variety of malignant cell lines, including human cervical carcinoma HeLa cells. In this study, we found that NCTD-activated p38 mitogen-activated protein kinase (p38 MAPK)-nuclear transcription factor kappa B (NF-?B) signaling pathway induced mitochondrial apoptotic pathway activation and G2/M cell cycle arrest in HeLa cells. NCTD-induced mitochondria-associated apoptosis was concomitant with the collapse of mitochondrial membrane potential (??(m)), translocation of Bax, down-regulation of Bcl-2 expression, and release of cytochrome c. NCTD-led G2/M cell-cycle arrest was associated with the up-regulated p21 and p-cdc25c expression and the down-regulated cyclin B and cdc2 expression. Treatment of the cells with p38 inhibitor SB203580 and NF-?B inhibitor pyrrolidine dithiocarbamate (PDTC) showed that p38 functioned upstream of NF-?B, while augmented apoptosis and cell cycle arrest were induced in response to NCTD with NF-?B activation. Intriguingly, NF-?B had a negative feedback regulatory effect on p38 activation. Moreover, NCTD-induced apoptosis and cell cycle arrest were significantly blocked by SB203580 and PDTC but not by pifithrin-? (p53 inhibitor). Therefore, p38-NF-?B induced mitochondrial apoptotic pathway and G2/M cell cycle arrest in NCTD-treated HeLa cells. PMID:23281704

Dong, Xiu; Li, Jian-Chun; Jiang, Yuan-Yuan; Xia, Ming-Yu; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2012-01-01

274

Design of online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) hyphenated systems for quantitative analysis of small organic compounds in biological matrices.  

PubMed

Three online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method examples are presented where two different types of chromatographic columns or solvent systems were coupled to meet specific analytical objectives: (i) SPE of target analytes by restricted access media from high ionic strength urine matrix was coupled with reversed phase LC-MS/MS conditions accommodating high ionization potentials of the analytes (urinary bisphenol A and other phenolic derivatives); (ii) strong cation exchange SPE of analytes of diverse polarity and pK(a) was coupled with reversed phase LC-MS/MS analysis (urinary atrazine metabolites); (iii) pre-concentration of low pg per sample analytes by weak anion exchange SPE was hyphenated with ion pair LC-MS analysis (intracellular nucleotide triphosphate analogs). With these examples we suggest a conductive generic work flow for the development of online SPE-LC-MS methods and show how advanced commercial LC devices and software allow for the design of complex yet highly versatile analytical separation systems suited to the unique physicochemical properties of the target analytes. PMID:22162441

Kuklenyik, Zsuzsanna; Calafat, Antonia M; Barr, John R; Pirkle, James L

2011-12-01

275

Apoptosis and Necrosis in the Liver  

PubMed Central

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

2013-01-01

276

APOPTOSIS: Mitochondria--the Death Signal Integrators  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Many of the intricate pathways of apoptosis that instruct a cell to kill itself involve the convergence of key proteins on the membranes of mitochondria. Such proteins induce the permeabilization of mitochondrial membranes and the release of caspase enzymes and nuclease activators that set in motion the final stages of programmed cell death. Now, as Brenner and Kroemer discuss in their Perspective, a proapoptotic transcription factor called TR3 has been found to move from its normal location in the nucleus to the mitochondria and to promote release of cytochrome c, a key event in apoptosis (Li et al.)

Catherine Brenner (Institut Gustave Roussy; Université de Technologie de Compiègne ;Apoptosis, Cancer and Immunity Laboratory associated with the National League Against Cancer); Guido Kroemer (Institut Gustave Roussy; Université de Technologie de Compiègne ;Apoptosis, Cancer and Immunity Laboratory associated with the National League Against Cancer)

2000-08-18

277

APOPTOSIS: Till Death Us Do Part  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Epithelial cells need to remain firmly attached to each other and to the extracellular matrix. In the event that these cells become detached, they undergo apoptosis. In a Perspective, Hunt and Evan discuss new work that identifies the trigger that sets in motion the apoptosis program following detachment (Puthalakath et al.). The trigger turns out to be the pro-apoptotic protein Bmf. This protein is attached to the myosin V motor complex of the actin cytoskeleton under normal conditions, but is set free once cells become detached.

Abigail Hunt (University of California-San Francisco Cancer Center;); Gerard Evan (University of California-San Francisco Cancer Center;)

2001-09-07

278

Chemopreventive Effects of Sarcotriol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice  

PubMed Central

Sarcotriol (ST) has been shown to be chemopreventive on 7,12-dimethyl-benz(a)anthracene (DMBA) initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor development in CD-1 mice in recent studies from our laboratory. The objective of this study was to determine the chemopreventive effects of ST on ultraviolet B (UVB)-induced skin tumor development in female SKH-1 hairless mice, an experimental model relevant to human skin cancer development, and its possible mechanisms of action. Female SKH-1 mice were divided into two groups: Control and ST treated. Control was topically treated with 100 ?L acetone and ST treated group administered with 30 ?g ST in 100 ?L acetone one hour before UVB exposure. For UVB-induced tumorigenesis, carcinogenesis was initiated and promoted by UVB (180 mJ/cm2). Group weights and tumor counts were taken once every week. After 30 weeks, mice were sacrificed and dorsal skin samples were collected. The proteins from the skin sample were further used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8, caspase-9 and p53. Tumor multiplicity was found 19.6, 5.2 in the control and ST treated groups respectively. Caspase-3, -8, -9 and p53 were significantly (P < 0.05) upregulated in ST treated group compared to Control group. Together, this study for the first time identifies the chemopreventive effects of ST in UVB-induced carcinogenesis possibly by inducing apoptosis and upregulating p53. PMID:18463728

Kundoor, Vipra; Zhang, Xiaoying; Bommareddy, Ajay; Khalifa, Sherief; Fahmy, Hesham; Dwivedi, Chandradhar

2007-01-01

279

Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice  

PubMed Central

Sarcophine-diol (SD), one of the structural modifications of sarcophine, has shown chemopreventive effects on 12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor development in female CD-1 mice. The objective of this study was to determine the chemopreventive effects of SD on UVB-induced skin tumor development in hairless SKH-1 mice, a model more relevant to human skin cancer, and to determine the possible mechanisms of action. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into two groups having 27 mice in each group: control and SD treatment. The control group was topically treated with 100 ?L acetone and SD treatment group was topically treated with SD (30 ?g/100 ?L in acetone) 1 hour before each UVB radiation for 32 weeks. Tumor counts were recorded on a weekly basis for 30 weeks. Effects of SD on the expression of caspases were investigated to elucidate the possible mechanism of action. The proteins from epidermal homogenates of experimental mice were used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8 and caspase-9 respectively. TUNEL assay was used for determining DNA fragmented apoptotic cells in situ. Results showed that at the end of experiment, tumor multiplicity in control and SD treatment groups was 25.8 and 16.5 tumors per mouse respectively. Furthermore, Topical treatment of SD induced DNA fragmented apoptotic cells by upgrading the expressions of cleaved caspase-3 and caspase-8. This study clearly suggested that SD could be an effective chemopreventive agent for UVB-induced skin cancer by inducing caspase dependent apoptosis. PMID:19597578

Zhang, Xiaoying; Bommareddy, Ajay; Chen, Wei; Hildreth, Michael B.; Kaushik, Radhey S.; Zeman, David; Khalifa, Sherief; Fahmy, Hesham; Dwivedi, Chandradhar

2009-01-01

280

Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading  

Microsoft Academic Search

PurposeThe purpose of this study was to determine whether bisphosphonate treatment can prevent or delay osteocyte apoptosis in a cyclic fatigue animal model and if there are differences between two different bisphosphonates in their effects on osteocyte apoptosis.

Helene Follet; Jiliang Li; Roger J. Phipps; Siu Hui; Keith Condon; David B. Burr

2007-01-01

281

The SpeX Prism Library: 1000+ low-resolution, near-infrared spectra of ultracool M, L, T and Y dwarfs  

NASA Astrophysics Data System (ADS)

The SpeX Prism Library (SPL) is a uniform compilation of low-resolution (?/?? ? 75-120), near-infrared (0.8--2.5 ?m) spectra spanning a decade of observations with the IRTF SpeX spectrograph. Primarily containing ultracool M, L, T and Y dwarfs, this spectral library has been used in over 100 publications to date, facilitating a broad range of science on low mass stars, exoplanets, high redshift sources and instrument/survey design. I summarize the contents of the SPL and highlight a few of the key scientific results that have made use of this resource, as well as applications in education, outreach and art. I also outline the future plans of the SPL, which include a reanalysis of early data, better integration and dissemination of source and spectral metadata, conversion to Virtual Observatory formats, development of a Python software package for community analysis, and a design for a node-based visual programming platform that can facilitate citizen science and project-based learning in stellar spectroscopy. http://www.browndwarfs.org/spexprism

Burgasser, Adam J.

282

The SpeX Prism Library: 1000+ Low-resolution, Near-infrared Spectra of Ultracool M, L, T and Y Dwarfs  

E-print Network

The SpeX Prism Library (SPL) is a uniform compilation of low-resolution (R ~ 75-120), near-infrared (0.8-2.5 micron) spectra spanning a decade of observations with the IRTF SpeX spectrograph. Primarily containing ultracool M, L, T and Y dwarfs, this spectral library has been used in over 100 publications to date, facilitating a broad range of science on low mass stars, exoplanets, high redshift sources and instrument/survey design. I summarize the contents of the SPL and highlight a few of the key scientific results that have made use of this resource, as well as applications in education, outreach and art. I also outline the future plans of the SPL, which include a reanalysis of early data, better integration and dissemination of source and spectral metadata, conversion to Virtual Observatory formats, development of a Python software package for community analysis, and a design for a node-based visual programming platform that can facilitate citizen science and project-based learning in stellar spectroscopy.

Burgasser, Adam J

2014-01-01

283

Ultrasound-assisted magnetic SPE based on Fe3O4-grafted graphene for the determination of polychlorinated biphenyls in water samples.  

PubMed

An ultrasound-assisted magnetic SPE procedure with an Fe3 O4 -grafted graphene nanocomposite as the magnetic adsorbent has been developed to determine seven polychlorinated biphenyls (PCBs; PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, and PCB180) simultaneously in 200 mL environmental water samples, in combination with GC-MS/MS. Several factors related to magnetic SPE efficiencies, such as the superparamagnetic intensity and amount of adsorbent, extraction time, sample pH, and desorption conditions were investigated. With the assistance of ultrasound, the extraction achieved the maximum within only 20 s, attributed to the powerful adsorptive ability of the magnetic adsorbent toward the PCBs. Under the optimized conditions, an excellent linearity was observed in the range of 0.1-100 ng/L for PCB28, 0.2-100 ng/L for PCB52, and 0.5-100 ng/L for the other five PCBs with the correlation coefficients ranging from 0.9988 to 0.9996. The mean recoveries at spiked levels of 5.0 and 10.0 ng/L were 84.9-108.5%, the coefficients of variations were <6.5%. With convenient magnetic separation, the synthesized magnetic adsorbent could be recycled more than ten times. The proposed method was demonstrated to be feasible, simple, rapid, and easy to operate for the trace analysis of the PCBs in environmental water samples. PMID:24030865

Cao, Xiaoji; Chen, Jiaoyu; Ye, Xuemin; Zhang, Feifei; Shen, Lingxiao; Mo, Weimin

2013-11-01

284

Mixed-mode SPE for a multi-residue analysis of benzodiazepines in whole blood using rapid GC with negative-ion chemical ionization MS.  

PubMed

A sensitive and selective method for simultaneous quantitation of 15 benzodiazepines in human whole blood using rapid GC with negative-ion chemical ionization MS is proposed. A mixed-mode cation-exchange polymeric sorbent was used for SPE. Different extraction solvents or mixtures of solvents of different compositions for elution of the adsorbed analytes, and washing steps for eliminating interferences in the column were tested. Analytes were eluted from the column using 5% v/v NH4 OH in methanol. A derivatization step using different silylation reagents, time, and temperature was tested. Extracts from SPE were silylated by a mixture of N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide, acetonitrile, ethyl acetate, and subjected to gas chromatographic analysis. The LODs of 15 benzodiazepines in whole blood samples ranged from 0.24-0.62 ng mL(-1). The RSDs of samples used for three different quality control concentration levels were lower than 7.0%, and the accuracy ranged from 89.5 to 110.5%. The results show that the developed method is accurate, sensitive, selective, and very fast. Finally, the applicability of this method for determination of trace concentrations of several benzodiazepines in real blood samples has been demonstrated. PMID:23505213

Karlonas, Nerijus; Padarauskas, Audrius; Ramanavicius, Arunas; Ramanaviciene, Almira

2013-04-01

285

Death from within: apoptosis and the secretory pathway  

Microsoft Academic Search

Recent studies have highlighted the importance of the secretory pathway in stress-induced apoptotic signaling. Sensing stress at the endoplasmic reticulum and Golgi might first trigger recovery mechanisms, followed by apoptosis if repair is unsuccessful. Cleavage of endoplasmic-reticulum- or Golgi-resident proteins can signal repair or apoptosis and promote organelle disassembly during apoptosis. Initiation of apoptosis from the secretory pathway requires components

Rebecca S Maag; Stuart W Hicks; Carolyn E Machamer

2003-01-01

286

Apoptosis in animal models of virus-induced disease  

Microsoft Academic Search

Apoptosis is associated with virus-induced human diseases of the central nervous system, heart and liver, and causes substantial morbidity and mortality. Although virus-induced apoptosis is well characterized in individual cells in cell culture, virus-induced apoptosis in vivo and the role of apoptosis in virus-induced disease is not well established. This Review focuses on animal models of virus-induced diseases of the

Kenneth L. Tyler; Penny Clarke

2009-01-01

287

Regulation and critical role of potassium homeostasis in apoptosis  

Microsoft Academic Search

Programmed cell death or apoptosis is broadly responsible for the normal homeostatic removal of cells and has been increasingly implicated in mediating pathological cell loss in many disease states. As the molecular mechanisms of apoptosis have been extensively investigated a critical role for ionic homeostasis in apoptosis has been recently endorsed. In contrast to the ionic mechanism of necrosis that

Shan Ping Yu

2003-01-01

288

Apoptosis in plants : does it exist?  

Microsoft Academic Search

Programmed cell death is an essential part of the live of any organism; it shapes the body and organs and plays an important role in the response to adverse environmental conditions and attack by a variety of pathogenic organisms. The mechanisms by which PCD is executed are diverse. In animal cells two main types of PCD have been described: apoptosis

E. J. Woltering; Doorn van W. G

2005-01-01

289

Farnesol-induced apoptosis in Candida albicans.  

PubMed

Farnesol, a precursor in the isoprenoid/sterol pathway, was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. Farnesol is involved in the inhibition of germination and biofilm formation by C. albicans and can be cytotoxic at certain concentrations. In addition, we have shown that farnesol can trigger apoptosis in mammalian cells via the classical apoptotic pathways. In order to elucidate the mechanism behind farnesol cytotoxicity in C. albicans, the response to farnesol was investigated, using proteomic analysis. Global protein expression profiles demonstrated significant changes in protein expression resulting from farnesol exposure. Among the downregulated proteins were those involved in metabolism, glycolysis, protein synthesis, and mitochondrial electron transport and the respiratory chain, whereas proteins involved in folding, protection against environmental and oxidative stress, actin cytoskeleton reorganization, and apoptosis were upregulated. Cellular changes that accompany apoptosis (regulated cell death) were further analyzed using fluorescent microscopy and gene expression analysis. The results indicated reactive oxygen species accumulation, mitochondrial degradation, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) in the farnesol-exposed cells concurrent with increased expression of antioxidant-encoding and drug response genes. More importantly, the results demonstrated farnesol-induced upregulation of the caspase gene MCA1 and the intracellular presence of activated caspases. In conclusion, this study demonstrated that farnesol promotes apoptosis in C. albicans through caspase activation, implying an important physiological role for farnesol in the fungal cell life cycle with important implications for adaptation and survival. PMID:19364863

Shirtliff, Mark E; Krom, Bastiaan P; Meijering, Roelien A M; Peters, Brian M; Zhu, Jingsong; Scheper, Mark A; Harris, Megan L; Jabra-Rizk, Mary Ann

2009-06-01

290

Original article Apoptosis of polymorphonuclear leukocytes  

E-print Network

PMN was observed by histochemical stain- ing for myeloperoxidase (MPO) and electron microscopy the stimulation. Apoptosis of PMN and phagocytosis by macrophages may represent a removal mechanism, 33]. Moreover, apoptotic PMN are promptly removed by the macrophages (MAC) before they can support

Paris-Sud XI, Université de

291

A novel method for detection of apoptosis  

SciTech Connect

There are two different Angiotensin II (ANG II) peptides in nature: Human type (ANG II) and Bovine type (ANG II*). These eight amino acid peptides differ only at position 5 where Valine is replaced by Isoleucine in the Bovine type. They are present in all species studied so far. These amino acids are different by only one atom of carbon. This difference is so small, that it will allow any of ANG II, Bovine or Human antibodies to interact with all species and create a universal method for apoptosis detection. ANG II concentrations are found at substantially higher levels in apoptotic, compared to non-apoptotic, tissues. ANG II accumulation can lead to DNA damage, mutations, carcinogenesis and cell death. We demonstrate that Bovine antiserum can be used for universal detection of apoptosis. In 2010, the worldwide market for apoptosis detection reached the $20 billion mark and significantly increases each year. Most commercially available methods are related to Annexin V and TUNNEL. Our new method based on ANG II is more widely known to physicians and scientists compared to previously used methods. Our approach offers a novel alternative for assessing apoptosis activity with enhanced sensitivity, at a lower cost and ease of use.

Zagariya, Alexander M., E-mail: zagariya@uic.edu

2012-04-15

292

Measuring apoptosis in mammals in vivo.  

PubMed

Apoptosis is a mode of cell death that is essential in multicellular organisms for the removal of superfluous, damaged, or potentially dangerous cells during development, infection, or normal tissue homeostasis. To prevent inflammation, cells undergoing apoptosis produce "find-me" signals that trigger the recruitment of phagocytes, which clear the apoptotic cells on recognition of "eat-me" signals. Despite the loss of billions of cells per day by apoptosis in the human body, the number of apoptotic cells found in healthy tissue is surprisingly low and reflects the efficiency of this process. However, in certain conditions (e.g., in cancer cells responding to chemotherapy), the number of apoptotic cells is too high to be efficiently cleared by phagocytes, and apoptotic cells can be observed. In these situations, the detection of apoptosis may be helpful in monitoring disease progression as well as in predicting the responses of tumors to anticancer therapies. Here we introduce various methods for monitoring apoptotic cells in vivo using a murine model of B-cell lymphoma and a solid tumor xenograft. PMID:25368316

Newbold, Andrea; Martin, Ben P; Cullinane, Carleen; Bots, Michael

2014-01-01

293

THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY  

EPA Science Inventory

Apoptosis, a form of programmed cell death, occurs in the nervous system throughout development, but with a preponderance of cell death occurring during the prenatal and perinatal periods. Aberrant periods of increased or decreased cell death, induced by toxicants in air, water,...

294

Sodium orthovanadate inhibits p53-mediated apoptosis.  

PubMed

Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) alpha. We compared the effects of vanadate to PFTalpha and PFTmicro, an inhibitor of transcription-independent apoptosis by p53. Vanadate suppressed p53-associated apoptotic events at the mitochondria, including the loss of mitochondrial membrane potential, the conformational change of Bax and Bak, the mitochondrial translocation of p53, and the interaction of p53 with Bcl-2. Similarly, vanadate suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of SaOS-2 cells. In radioprotection assays, which rely on p53, vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Together, our findings indicated that vanadate effectively suppresses p53-mediated apoptosis by both transcription-dependent and transcription-independent pathways, and suggested that both pathways must be inhibited to completely block p53-mediated apoptosis. PMID:20048077

Morita, Akinori; Yamamoto, Shinichi; Wang, Bing; Tanaka, Kaoru; Suzuki, Norio; Aoki, Shin; Ito, Azusa; Nanao, Tomohisa; Ohya, Soichiro; Yoshino, Minako; Zhu, Jin; Enomoto, Atsushi; Matsumoto, Yoshihisa; Funatsu, Osamu; Hosoi, Yoshio; Ikekita, Masahiko

2010-01-01

295

Apoptosis, Heart Failure, Ischemic Heart Disease  

Microsoft Academic Search

Cardiomyocytes die by apoptosis in addition to necrosis under a variety of pathological conditions including heart failure, cardiomyopathy, and ischemia\\/reperfusion. This review summarizes current status of the literature demonstrating evidence of apoptotic cell death in heart failure and ischemic heart disease. Apoptotic cells have been detected in failing hearts of human and dog. Ischemia up to 2 hr does not

Nilanjana Maulik; Dipak K. Das

1999-01-01

296

Induction of Apoptosis by Cancer Chemotherapy  

Microsoft Academic Search

Studies performed over the past five years have demonstrated that there are two major cell-intrinsic pathways for inducing apoptosis, one that begins with ligation of cell surface death receptors and another that involves mitochondrial release of cytochrome c. Several reports have suggested that anticancer drugs kill susceptible cells by inducing expression of death receptor ligands, especially Fas ligand (FasL). Other

Scott H. Kaufmann; William C. Earnshaw

2000-01-01

297

Proliferation, cell cycle and apoptosis in cancer  

Microsoft Academic Search

Beneath the complexity and idiopathy of every cancer lies a limited number of 'mission critical' events that have propelled the tumour cell and its progeny into uncontrolled expansion and invasion. One of these is deregulated cell proliferation, which, together with the obligate compensatory suppression of apoptosis needed to support it, provides a minimal 'platform' necessary to support further neoplastic progression.

Gerard I. Evan; Karen H. Vousden

2001-01-01

298

Apoptosis. The role of the endonuclease.  

PubMed Central

Cell death by apoptosis mediates several important physiologic and pathologic processes and appears to be intrinsically programmed. Its characteristic features are distinctive morphologic changes of nucleus and cytoplasm, along with cleavage of chromatin at regularly spaced sites. Here we study DNA organization and nuclear structure in apoptotic thymocytes to define the cleavage event and, by implication, the role of the responsible endonuclease. We show that in apoptosis, double-stranded cleavage of DNA generates two classes of chromatin fragments: 70% of DNA exists as long, H1-rich oligonucleosomes bound to the nucleus, and 30% comprises short oligonucleosomes and mononucleosomes, which are depleted in H1, enriched in HMG1 and 2, and not attached to the nucleus. This minority class probably derives from chromatin in a transcriptionally active configuration, which would allow better access to enzymes in the nucleoplasm, producing more complete digestion. The characteristic nucleolar morphology in apoptosis can also be explained in terms of cleavage of the transcriptionally active ribosomal genes, with conservation of the nucleolin-rich fibrillar center. The chromatin cleavage, nucleolar morphologic changes, and chromatin condensation were closely mimicked by micrococcal nuclease digestion of normal thymocyte nuclei in the presence of protease inhibitors. Thus, in apoptosis, selective activation of an endogenous endonuclease appears to be responsible not only for widespread chromatin cleavage but also for the major nuclear morphologic changes. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 Figure 6 Figure 8 Figure 9 Figure 10 PMID:2156431

Arends, M. J.; Morris, R. G.; Wyllie, A. H.

1990-01-01

299

Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines  

Microsoft Academic Search

Since apoptosis is the primary mode of cell death induced by cisplatin, the role of apoptosis and apoptosis-related gene products\\u000a in cisplatin resistance was investigated in four human cisplatin-resistant cell lines of different tumour type. A common feature\\u000a of the resistant sublines was a reduced susceptibility to drug-induced apoptosis compared to parental sensitive lines. Loss\\u000a of wild-type p53 function was

P. Perego; S. C. Righetti; R. Supino; D. Delia; C. Caserini; N. Carenini; B. Bedogné; E. Broome; S. Krajewski; J. C. Reed; F. Zunino

1997-01-01

300

Apoptosis and hematopoiesis in murine fetal liver.  

PubMed

The fetal mouse liver (FL) is an organ of intense, but transient, hematopoietic activity during mid-gestation, with erythropoiesis being predominant during days 11 through 16. It therefore seemed reasonable to expect that hematopoietic cytokines, such as erythropoietin (epo), interleukin-3 (IL-3), and stem cell factor (SCF), may play important roles in maintaining a homeostatic balance of erythropoiesis and apoptosis in liver during ontogeny. First, we determined the effects of these growth factors on hematopoiesis by measuring colony formation and hemoglobin synthesis of cultured FLs. Secondly, we determined the protection from apoptosis afforded by these cytokines, using electrophoretic analysis of DNA and by flow cytometry of FL cells deprived in culture of epo, IL-3, and SCF. Erythropoietin was necessary and alone sufficient for hemoglobin synthesis in colony-forming units-erythroid colonies, but IL-3 was a required cofactor to obtain maximal development of burst-forming units-erythroid colonies. SCF alone caused little colony formation in methylcellulose cultures of FLs, but when combined with epo and IL-3, it had dramatic effects both on the number of colonies and their size. Secondly, indices of apoptosis were determined by measuring DNA fragmentation caused by endogenous nuclease activity in apoptotic cells. Liver cells from cultures without cytokines showed the extensive degradation of DNA to low molecular weight nucleosomal oligomers, which is characteristic of apoptosis. Protection from apoptosis afforded by epo directly corresponded to the level of erythropoiesis in FLs of different gestational age. Erythropoietin was by far the most critical cytokine in sparing FL cells from apoptosis. Analyses of agarose gels showed that SCF and IL-3 alone had no apparent effect in reducing the amount of DNA in fragments, and when combined with epo they had no more protective effect than that provided by epo alone. However, using the more sensitive flow cytometric determination of cells with subdiploid amounts of DNA, SCF, and IL-3 alone had measurable protective effects that were less than those caused by epo. Thus, we show that normal, untransformed cells of the developing hematopoietic system not only require cytokines for proliferation and differentiation, but they have an initial and absolute requirement of them for protection from apoptosis. PMID:7678514

Yu, H; Bauer, B; Lipke, G K; Phillips, R L; Van Zant, G

1993-01-15

301

Participation of chloroplasts in plant apoptosis.  

PubMed

Mitochondria are known to participate in the initiation of programmed cell death (PCD) in animals and in plants. The role of chloroplasts in PCD is still unknown. We describe a new system to study PCD in plants; namely, leaf epidermal peels. The peel represents a monolayer consisting of cells of two types: phototrophic (guard cells) and chemotrophic (epidermal cells). The peels from pea (Pisum sativum L.) leaves were treated by cyanide as an inducer of PCD. We found an apoptosis-enhancing effect of illumination on chloroplast-containing guard cells, but not on chloroplastless epidermal cells. Antioxidants and anaerobiosis prevented the CN(-)-induced apoptosis of cells of both types in the dark and in the light. On the other hand, methyl viologen and menadione known as ROS-generating reagents as well as the Hill reaction electron acceptors (BQ, DAD, TMPD, or DPIP) that are not oxidized spontaneously by O2 were shown to prevent the CN(-)-induced nucleus destruction in guard cells. Apoptosis of epidermal cells was potentiated by these reagents, and they had no influence on the CN- effect. The light-dependent activation of CN(-)-induced apoptosis of guard cells was suppressed by DCMU, stigmatellin or DNP-INT, by a protein kinase inhibitor staurosporine as well as by cysteine and serine protease inhibitors. The above data suggest that apoptosis of guard cells is initiated upon a combined action of two factors, i.e., ROS and reduced plastoquinone of the photosynthetic electron transfer chain. As to reduction of ubiquinone in the mitochondrial respiratory chain, it seems to be antiapoptotic for the guard cell. PMID:14570380

Samuilov, Vitaly D; Lagunova, Elena M; Kiselevsky, Dmitry B; Dzyubinskaya, Elena V; Makarova, Yana V; Gusev, Mikhail V

2003-01-01

302

Apoptosis repressor with caspase recruitment domain modulates second mitochondrial-derived activator of caspases mimetic-induced cell death through BIRC2/MAP3K14 signalling in acute myeloid leukaemia.  

PubMed

Overexpression of the apoptosis repressor with caspase recruitment domain (ARC, also termed NOL3) protein predicts adverse outcome in patients with acute myeloid leukaemia (AML) and confers drug resistance to AML cells. The second mitochondrial-derived activator of caspases (SMAC, also termed DIABLO) mimetic, birinapant, promotes extrinsic apoptosis in AML cells. SMAC mimetics induce cleavage of cellular inhibitor of apoptosis (cIAP) proteins, leading to stabilization of the nuclear factor-?B (NF-?B)-inducing kinase (MAP3K14, also termed NIK) and activation of non-canonical NF-?B signalling. To enhance the therapeutic potential of SMAC mimetics in AML, we investigated the regulation and role of ARC in birinapant-induced apoptosis. We showed that birinapant increases ARC in AML and bone marrow-derived mesenchymal stromal cells (MSCs). Downregulation of MAP3K14 by siRNA decreased ARC levels and suppressed birinapant-induced ARC increase. Reverse-phase protein array analysis of 511 samples from newly diagnosed AML patients showed that BIRC2 (also termed cIAP1) and ARC were inversely correlated. Knockdown of ARC sensitized, while overexpression attenuated, birinapant-induced apoptosis. Furthermore, ARC knockdown in MSCs sensitized co-cultured AML cells to birinapant-induced apoptosis. Our data demonstrate that ARC is regulated via BIRC2/MAP3K14 signalling and its overexpression in AML or MSCs can function as a resistant factor to birinapant-induced leukaemia cell death, suggesting that strategies to inhibit ARC will improve the therapeutic potential of SMAC mimetics. PMID:25079338

Mak, Po Y; Mak, Duncan H; Ruvolo, Vivian; Jacamo, Rodrigo; Kornblau, Steven M; Kantarjian, Hagop; Andreeff, Michael; Carter, Bing Z

2014-11-01

303

Molecular mechanisms of liver injury: apoptosis or necrosis.  

PubMed

Hepatic apoptosis is thought of as a prevalent mechanism in most forms of liver injury. However, the role of hepatic apoptosis is often intermixed with the cellular necrosis. It remains unknown how apoptosis is relevant to the progression of the liver injury. This review summarizes the characteristics of both hepatic apoptosis and necrosis in pathogenesis of liver diseases. Apoptosis and necrosis represent alternative outcomes of different etiology during liver injury. Apoptosis is a main mode of cell death in chronic viral hepatitis, but is intermingled with necrosis in cholestatic livers. Necrosis is the principal type of liver cell killing in acetaminophen-induced hepatotoxicity. Anti-apoptosis as a strategy is beneficial to liver repair response. Therapeutic options of liver disease depend on the understanding toward pathogenic mechanisms of different etiology. PMID:24867271

Wang, Kewei

2014-10-01

304

Determination of fluoroquinolones in bovine milk samples using a pipette-tip SPE step based on multiwalled carbon nanotubes prior to CE separation.  

PubMed

A simple CE-UV method was developed for the simultaneous determination of ciprofloxacin, norfloxacin, and ofloxacin in milk samples. The optimum separation was obtained using a 20 mM ammonium dihydrogenphosphate solution with 2 mM cetyltrimethylammonium bromide at pH 3.0 as the BGE. Satisfactory resolution for structurally very similar analytes, like norfloxacin and ciprofloxacin, was achieved without including any organic solvent. Milk samples were prepared using a simple/extraction procedure based on acidic protein precipitation followed by an SPE step using only 5 mg of multiwalled carbon nanotubes as the sorbent material. The LODs for the three compounds were between 7.5 and 11.6 ?g/L and the RSDs for the peak areas were between 2.6 and 4.9%. The complete method was applied to spiked real milk samples with satisfactory recoveries for all analytes (84-106%). PMID:24227292

Springer, Valeria; Jacksén, Johan; Ek, Patrik; Lista, Adriana G; Emmer, Asa

2014-01-01

305

Rapid isolation and identification of minor natural products by LC-MS, LC-SPE-NMR and ECD: isoflavanones, biflavanones and bisdihydrocoumarins from Ormocarpum kirkii.  

PubMed

The combination of the hyphenated techniques LC-MS and LC-SPE-NMR constitutes a powerful platform for the rapid isolation and identification of minor components from natural sources. Electronic circular dichroism (ECD) is a useful tool to determine the absolute configuration of small quantities of chiral molecules. In order to search for minor constituents present in an Ormocarpum kirkii extract, these techniques were applied for the separation and structure elucidation of a series of isoflavanones, biflavanones and biscoumarins. After optimization of chromatographic conditions and subsequent isolation, MS and 1D and 2D NMR data were collected. Experimental and calculated ECD spectra were used in conjunction with NMR data to confirm the absolute configuration of these compounds. Eight compounds were identified for the first time and six have been previously reported. The present approach offers a strategy for accelerating research on natural products. PMID:22575670

Xu, Yong-Jiang; Foubert, Kenn; Dhooghe, Liene; Lemière, Filip; Maregesi, Sheila; Coleman, Christina M; Zou, Yike; Ferreira, Daneel; Apers, Sandra; Pieters, Luc

2012-07-01

306

On-flow pulsed field gradient heteronuclear correlation spectrometry in off-line LC-SPE-NMR analysis of chemicals related to the chemical weapons convention.  

PubMed

Hyphenation of liquid chromatography with nuclear magnetic resonance spectroscopy (LC-NMR) is a useful technique in the analysis of complex samples. However, application of on-flow 1H NMR spectrometry during the LC-NMR analysis usually suffers from high intensity of eluent resonances. The poor dynamic range can be improved either with use of deuterated eluents or with various signal suppression schemes. Deuterated eluents are expensive, and peak-selective signal suppression schemes are often unsatisfactory when detection of chemicals at low concentration is needed. If the analytes have a common heteronucleus, on-flow pulsed field gradient heteronuclear correlation spectrometry can offer several benefits. The analytes can be monitored selectively, while the intense nondeuterated eluent and impurity background can be effectively eliminated. In our study, on-flow one-dimensional (1D) 1H-31P heteronuclear single quantum coherence (HSQC) spectrometry was utilized in the analysis of characteristic organophosphorus degradation products of nerve agents sarin and soman during chromatographic separation. These chemicals were not detectable by UV, so their retention times were monitored using on-flow 1D 1H-31P HSQC. This enabled application of LC-NMR combined with solid-phase extraction (LC-SPE-NMR) in analysis of these organophosphorus chemicals in an alkaline decontamination solution. The analytes were extracted from the SPE cartridges with deuterated eluent, and the off-line NMR analysis was performed using a mass-sensitive microcoil probe head. The used on-flow 1D 1H-31P HSQC approach offered a high dynamic range and good detection limit (ca. 10 microg/55 nmol) with a high sampling frequency (1 point per 2 s) in the acquired pseudo-two-dimensional spectrum. No significant impurity background was present in the off-line NMR samples, and identification of the extracted analytes was straightforward. PMID:19128090

Koskela, Harri; Ervasti, Mia; Björk, Heikki; Vanninen, Paula

2009-02-01

307

Two novel zeolitic imidazolate frameworks (ZIFs) as sorbents for solid-phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs) in environmental water samples.  

PubMed

In this work, two novel zeolitic imidazolate framework (ZIF) materials, ZIF-7 and ZIF-11, were firstly introduced as solid-phase extraction (SPE) sorbents for PAHs efficient extraction and highly sensitive analysis in environmental water samples with high performance liquid chromatography (HPLC) coupled with fluorescence detection. ZIF-7 and ZIF-11 were successfully synthesized and characterized with SEM, FTIR, XRD and water contact angels, exhibiting unique and excellent stability, spatial structure and chemical composition, promising for environmental PAHs efficient enrichment through hydrophobic, ?-? and ?-complexation interactions. The topology effect on PAHs extraction was compared between ZIF-7 and ZIF-11, considering they have the same composition in metal ion (Zn(2+)) and organic linker, but differing spatial structures: ZIF-7 has a cubic structure, while ZIF-11 is a rhombic dodecahedron. At last, ZIF-11 with markedly better extraction efficiencies was selected for subsequent analysis. Under optimum extraction conditions such as sample volume, extraction time, desorption conditions, volume of organic modifier and salt concentration, a robust and highly efficient method based on ZIF-11 as a novel SPE sorbent has been successfully developed for environmental PAHs analysis. Satisfactory precision and accuracy ranging from 1-2.4 × 10(3) ng L(-1) as well as ultrasensitive detection limits of 0.08-1.6 ng L(-1) have been successfully achieved. Moreover, ZIF-11 extraction also exhibited high recoveries of 82.4-112.7% with relative standard deviations (RSDs) being less than 9% for PAHs in the environmental water samples. Therefore, our novel, convenient and efficient extraction method based on ZIF-11 as a sorbent is promising for applications in future trace-level environmental PAHs analyses. PMID:25209546

Hu, Huiping; Liu, Shengquan; Chen, Chunyan; Wang, Jianping; Zou, Ying; Lin, Lihua; Yao, Shouzhuo

2014-10-15

308

Outcompeting GC for the detection of legacy chlorinated pesticides: online-SPE UPLC APCI/MSMS detection of endosulfans at part per trillion levels.  

PubMed

Endosulfan, the last remaining organochlorine pesticide, has been the subject of a number of international regulations and restriction/banning action plans worldwide. Occurrence of endosulfan residues in South Florida environments has been widely described in the literature for more than two decades. This work describes a selective, sensitive, and fast online solid-phase extraction (SPE) method coupled with liquid chromatography separation and tandem mass spectrometry (LC-MS/MS) for the determination of endosulfan isomers and endosulfan sulfate in water samples at low part per trillion levels with very little sample preparation. A negative atmospheric pressure chemical ionization source was carefully optimized to produce reproducible spectra of the target compounds with no adduct ion formation. Selected reaction monitoring transitions were monitored and quantitation was performed against a per-deuterated internal standard ?-endosulfan (d4). The automated online SPE clean-up was performed using only 20 mL of untreated water sample prior to LC-MS/MS analysis. The method was capable of separating and quantifying endosulfan within a 24-min run using acetonitrile and water as mobile phases and presenting statistically calculated method detection limits of 3, 10, and 7 ng/L for endosulfan sulfate, ?-endosulfan, and ?-endosulfan, respectively. In addition, a QuEChERS method was successfully developed and applied for endosulfan determination in sediments/soils, floating and submerged algal mats, and small fish. Minimal matrix effects were observed in all matrices analyzed and recoveries for all analytes ranged from 50-144 %. The developed methodology was applied to monitor the occurrence and to assess the potential transport of endosulfan in the Loveland Slough watershed, an area adjacent to Everglades National Park showing long-term contamination with endosulfans. PMID:23386002

Quinete, Natalia; Wang, Jian; Fernandez, Adolfo; Castro, Joffre; Gardinali, Piero R

2013-07-01

309

FOXOs, cancer and regulation of apoptosis  

PubMed Central

Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of physiological and pathological processes including cancer. The importance of FOXO factors ascribes them under multiple levels of regulation including phosphorylation, acetylation/deacetylation, ubiquitination and protein–protein interactions. As FOXO factors play a pivotal role in cell fate decision, mounting evidence suggests that FOXO factors function as tumor suppressors in a variety of cancers. FOXOs are actively involved in promoting apoptosis in a mitochondria-independent and -dependent manner by inducing the expression of death receptor ligands, including Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, and Bcl-2 family members, such as Bim, bNIP3 and Bcl-XL, respectively. An understanding of FOXO proteins and their biology will provide new opportunities for developing more effective therapeutic approaches to treat cancer. PMID:18391973

Fu, Z; Tindall, DJ

2010-01-01

310

Ubiquitin-mediated regulation of apoptosis.  

PubMed

Ubiquitin is a protein modifier that is conjugated to target proteins either as a single moiety or as polyubiquitin chains. Over the past several years, an increasing number of ubiquitin ligases and ubiquitin-deconjugating enzymes have been identified; these modulate cell survival by degradative and non-degradative means. Mutations that affect ubiquitin-mediated signalling are tightly linked to various human pathologies including tumorigenesis. Unravelling how the ubiquitin-signal is conjugated, edited and 'read' is crucial to understanding cellular processes such as endocytic trafficking, NF-kappaB signalling, gene expression, DNA repair and apoptosis. In this review, we summarize recent advances that start to elucidate how the ubiquitin message is used as a versatile tool to regulate apoptosis, for example in the conjugation of ubiquitin to caspases. This results in steric interference with substrate entry and allosteric conformational impairment of the catalytic pocket of the caspase. PMID:19217783

Broemer, Meike; Meier, Pascal

2009-03-01

311

Increased neutrophil apoptosis in chronic fatigue syndrome  

PubMed Central

Background/Aims: Many patients with chronic fatigue syndrome (CFS) have symptoms that are consistent with an underlying viral or toxic illness. Because increased neutrophil apoptosis occurs in patients with infection, this study examined whether this phenomenon also occurs in patients with CFS. Methods: Apoptosis was assessed in patients with CFS in conjunction with concentrations of the anti-inflammatory cytokine, transforming growth factor ?1 (TGF?1). Results: The 47 patients with CFS had higher numbers of apoptotic neutrophils, lower numbers of viable neutrophils, increased annexin V binding, and increased expression of the death receptor, tumour necrosis factor receptor-I, on their neutrophils than did the 34 healthy controls. Patients with CFS also had raised concentrations of active TGF?1 (p < 0.005). Conclusions: These findings provide new evidence that patients with CFS have an underlying detectable abnormality in their immune cells. PMID:15280416

Kennedy, G; Spence, V; Underwood, C; Belch, J J F

2004-01-01

312

Apoptosis, Stem Cells, and Tissue Regeneration  

NSDL National Science Digital Library

Tissue regeneration after wounding or amputation generally requires cell proliferation. Work in several model organisms, including Drosophila, Hydra, Xenopus, and mouse, revealed a surprising function for caspases in cell proliferation after tissue damage, in addition to their known role in a form of cell death called apoptosis. In apoptotic cells, caspases can stimulate the production of secreted cytokines, such as Wnt, bone morphogenetic protein (BMP), transforming growth factor–β (TGF-β), Hedgehog family members, and prostaglandins, which in turn induce proliferation of neighboring cells, thus promoting tissue regeneration and homeostasis. These pathways can also contribute to tumorigenesis. This Review summarizes findings on this phenomenon, termed “apoptosis-induced compensatory proliferation,” and contains three figures and 110 references.

Andreas Bergmann (MD Anderson Cancer Center;Department of Biochemistry and Molecular Biology REV); Hermann Steller (Rockefeller University;Howard Hughes Medical Institute REV)

2010-10-26

313

Eosinophil Apoptosis and Clearance in Asthma  

PubMed Central

Asthma is an increasingly common respiratory condition characterized by reversible airway obstruction, bronchial hyper-responsiveness and airway inflammation with a clear unmet need for more effective therapy. Eosinophilic asthma is a phenotype of the condition that features increased blood or sputum eosinophils whose numbers correlate with disease severity. Several lines of evidence are now emerging, which implicate increased persistence of eosinophils in the lungs of patients with asthma as a consequence of inhibition of and defects in the apoptotic process, together with impaired apoptotic cell removal mechanisms. This article will update our knowledge of the mechanisms controlling eosinophil apoptosis and clearance, together with evidence implicating defects in apoptosis and pro-inflammatory cell removal in asthma. Recent developments in novel therapies for asthma that target eosinophil apoptotic and/or clearance pathways will also be discussed.

Walsh, Garry M

2013-01-01

314

Cardiolipin: Setting the beat of apoptosis  

Microsoft Academic Search

Cardiolipin (CL) is a mitochondria-specific phospholipid which is known to be intimately linked with the mitochondrial bioenergetic\\u000a machinery. Accumulating evidence now suggests that this unique lipid also has active roles in several of the mitochondria-dependant\\u000a steps of apoptosis. CL is closely associated with cytochrome c at the outer leaflet of the mitochondrial inner membrane. This interaction makes the process of

François Gonzalvez; Eyal Gottlieb

2007-01-01

315

HIV-1 protease-induced apoptosis  

PubMed Central

Background Apoptosis is one of the presumptive causes of CD4+ T cell depletion during HIV infection and progression to AIDS. However, the precise role of HIV-1 in this process remains unexplained. HIV-1 protease (PR) has been suggested as a possible factor, but a direct link between HIV-1 PR enzymatic activity and apoptosis has not been established. Results Here, we show that expression of active HIV-1 PR induces death in HeLa and HEK-293 cells via the mitochondrial apoptotic pathway. This conclusion is based on in vivo observations of the direct localization of HIV-1 PR in mitochondria, a key player in triggering apoptosis. Moreover, we observed an HIV-1 PR concentration-dependent decrease in mitochondrial membrane potential and the role of HIV-1 PR in activation of caspase 9, PARP cleavage and DNA fragmentation. In addition, in vitro data demonstrated that HIV-1 PR mediates cleavage of mitochondrial proteins Tom22, VDAC and ANT, leading to release of AIF and Hsp60 proteins. By using yeast two-hybrid screening, we also identified a new HIV-1 PR interaction partner, breast carcinoma-associated protein 3 (BCA3). We found that BCA3 accelerates p53 transcriptional activity on the bax promoter, thus elevating the cellular level of pro-apoptotic Bax protein. Conclusion In summary, our results describe the involvement of HIV-1 PR in apoptosis, which is caused either by a direct effect of HIV-1 PR on mitochondrial membrane integrity or by its interaction with cellular protein BCA3. PMID:24886575

2014-01-01

316

Targeting apoptosis pathways in cancer stem cells.  

PubMed

There is a significant void in cancer biology with regard to the elucidation of the mechanisms that underlie tumor formation and progression. Recently, the existence of a hierarchy within cancer cell populations has been demonstrated experimentally for several tumor types. The identification of a tumor cell subset that is capable of self-renewal and, concurrently, generation into more differentiated progeny has engendered new perspectives toward selective targeting of tumors. Although the identification of the so-called "cancer stem cells" (CSCs) is a leap in the study of cancer ontogenesis, therapeutic targeting of such cells is plagued by significant difficulties. CSCs are able to evade the control mechanisms that regulate cell survival and proliferation. Apoptosis is one of the most critical and well-studied mechanisms, governing tissue development and homeostasis through a complex network of molecules that mediate death and survival signals. Escape from such a finely tuned death program is a prerequisite for any tumor-initiating cell. Thus, many compounds have been developed to target cancer cells and induce apoptosis directly or indirectly. Several TRAIL receptor agonists are in Phase I or II trials, and IAP inhibitors are undergoing clinical examination to exploit their ability to enhance ionizing radiation- and chemotherapy-induced apoptosis. Further, the EGF-R/Akt pro-survival signaling axis is one of the most frequently explored sources of targets for indirect apoptosis induction, as evidenced by the significant amount of molecules designed to target this pathway and have been approved by the FDA or are under clinical evaluation. Despite the promise of these magic bullets, the absence of reliable clinical models has considerably diminished the therapeutic potential of targeted therapies considerably. A more systematic molecular characterization of the tumor-initiating cell population in many tumors will allow us to refine the stimuli that force CSCs to die, thus accelerating the development of more effective treatment for cancer. PMID:21315505

Signore, Michele; Ricci-Vitiani, Lucia; De Maria, Ruggero

2013-05-28

317

Apoptosis and its functional significance in molluscs  

Microsoft Academic Search

Programmed cell death leading to apoptosis is essential for normal development and homeostasis in plants and throughout the\\u000a animal kingdom. Although there are differences in apoptotic mechanisms between lower animals and vertebrates, crucial biochemical\\u000a components of the programmed cell death pathways remained remarkably conserved throughout evolution. Despite decades of studies\\u000a on the neurobiology and development of mollusks, comparatively little is

Tibor Kiss

2010-01-01

318

BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS  

Microsoft Academic Search

? Abstract Caspase activation plays a central role in the execution of apoptosis. The key components,of the biochemical,pathways,of caspase activation have been recently elucidated. In this review, we focus on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway,and the mitochondria- initiated pathway. In the cell surface death receptor pathway, activation of caspase-8 following its

Imawati Budihardjo; Holt Oliver; Michael Lutter; Xu Luo; Xiaodong Wang

1999-01-01

319

Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells  

PubMed Central

In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS) production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis. PMID:19405983

Kuo, Chen-Tzu; Chen, Bing-Chang; Yu, Chung-Chi; Weng, Chih-Ming; Hsu, Ming-Jen; Chen, Chien-Chih; Chen, Mei-Chieh; Teng, Che-Ming; Pan, Shiow-Lin; Bien, Mauo-Ying; Shih, Chung-Hung; Lin, Chien-Huang

2009-01-01

320

Courses: Nursing (NURS) Page 367Sonoma State University 2013-2014 Catalog nurS 313 BACCALAureAte nurSing perSpeCtiVeS ii (4)  

E-print Network

Courses: Nursing (NURS) Page 367Sonoma State University 2013-2014 Catalog nurS 313 BACCALAureAte nurSing perSpeCtiVeS ii (4) This course expands knowledge about the role of the professional nurse in society by exploring leadership and advocacy as integral components of professional nursing. It examines

Ravikumar, B.

321

1 S.R. REEVES, D.G. HILL, R.L. TINER, P.A. BASTIAN, M.W. CONWAY & S. MOHAGHEGH SPE 55627 Copyright 1999, Society of Petroleum Engineers Inc.  

E-print Network

1 S.R. REEVES, D.G. HILL, R.L. TINER, P.A. BASTIAN, M.W. CONWAY & S. MOHAGHEGH SPE 55627 Copyright adopted for the R&D program is a combination of conceptual methodology development, laboratory studies the industry today to focus on restimulation, GRI initiated a subsequent two-year R&D project in 1998

Mohaghegh, Shahab

322

Mechanisms and consequences of ebolavirus-induced lymphocyte apoptosis.  

PubMed

Ebolavirus (EBOV) is a member of the filovirus family and causes severe hemorrhagic fever, resulting in death in up to 90% of infected humans. EBOV infection induces massive bystander lymphocyte apoptosis; however, neither the cellular apoptotic pathway(s) nor the systemic implications of lymphocyte apoptosis in EBOV infection are known. In this study, we show data suggesting that EBOV-induced lymphocyte apoptosis in vivo occurs via both the death receptor (extrinsic) and mitochondrial (intrinsic) pathways, as both Fas-associated death domain dominant negative transgenic mice and mice overexpressing bcl-2 were resistant to EBOV-induced lymphocyte apoptosis. Surprisingly, inhibiting lymphocyte apoptosis during EBOV infection did not result in improved animal survival. Furthermore, we show for the first time that hepatocyte apoptosis likely occurs in EBOV infection, and that mice lacking the proapoptotic genes Bim and Bid had reduced hepatocyte apoptosis and liver enzyme levels postinfection. Collectively, these data suggest that EBOV induces multiple proapoptotic stimuli and that blocking lymphocyte apoptosis is not sufficient to improve survival in EBOV infection. These data suggest that hepatocyte apoptosis may play a role in the pathogenesis of EBOV infection, whereas lymphocyte apoptosis appears to be nonessential for EBOV disease progression. PMID:20028660

Bradfute, Steven B; Swanson, Paul E; Smith, Mark A; Watanabe, Eizo; McDunn, Jonathan E; Hotchkiss, Richard S; Bavari, Sina

2010-01-01

323

Dimethylfumarate induces apoptosis in human mast cells.  

PubMed

Mast cells modulate autoimmune diseases such as psoriasis and multiple sclerosis. Fumaric acid esters (FAEs) are widely used for the treatment of psoriasis, and dimethylfumarate (DMF) has recently been approved for multiple sclerosis. In this study, we analysed the cytotoxic effect of FAEs on human mast cells. Specifically, cell death was analysed in the human mast cell line HMC-1 and in primary cord blood-derived mast cells (CBMCs) after incubation with fumaric acid (FA), monomethylfumarate (MMF), DMF and calcium bis(monomethylfumarate) (Ca-MF). Our data show that only DMF potently induces apoptotic cell death in HMC-1 cells and CBMCs. DMF-mediated apoptosis was associated with increased expression of Bax and Bak and activation of caspase-9 and caspase-6. Interestingly, DMF also enhanced the sensitivity of CBMCs towards TRAIL- and dexamethasone-induced apoptosis. These findings demonstrate for the first time that DMF induces apoptosis of human mast cells, primarily via the mitochondrial apoptotic pathway. Our study contributes to the understanding of the beneficial effects of FAEs in autoimmune diseases and provides a rationale for exploiting FAEs for other diseases associated with mast cells. PMID:24112621

Förster, Anja; Preussner, Liane M; Seeger, Jens M; Rabenhorst, Anja; Kashkar, Hamid; Mrowietz, Ulrich; Hartmann, Karin

2013-11-01

324

Apoptosis in peri-implant tissue.  

PubMed

The authors examined 54 biopsies taken from the tissue surrounding loosened hip joint prostheses. In situ apoptotic cell identification was performed by the detection of single- and double-stranded DNA breaks that occurred in the early stages of apoptosis. Both types of breaks can be revealed by labeling the free 3'-OH termini with modified nucleotides (fluoresceine-dUTP) in an enzymatic reaction catalyzed by terminal deoxynucleotidyl transferase (TdT). Results were correlated with the presence of wear debris in the tissue and with the use of bone cement for prosthesis fixation. Apoptotic cells were present in a higher percentage in tissue sections where metal particles were present (24% apoptotic cells) if compared to areas where no wear (6%), or plastic wear (2.8%) or ceramic wear (1.5%) was observed. Apoptosis is neither related to bone cement, nor to the time it takes for the implant to fail. Cell death by apoptosis may be important in implants which release metal ions by corrosion or wear and may have been underestimated up to now, as it is a 'clean' way of cell death, leading to limited damage in the surrounding tissues. PMID:10850934

Stea, S; Visentin, M; Granchi, D; Cenni, E; Ciapetti, G; Sudanese, A; Toni, A

2000-07-01

325

Apoptosis induced by inhibition of intercellular contact  

PubMed Central

The LIM 1863 colon carcinoma cell line grows as structural organoids of goblet and columnar cells around a central lumen and provides a model for the development of stem cells in the normal colon. The organoid structure can be disrupted by removal of calcium from the medium, resulting in a suspension of single cells. Upon readdition of calcium, the cells reform the organoid structure over a period of 24 h, and ultrastructural examination of the reforming cells reveals that this involves a complex process that we have termed clutching. To determine the adhesion molecules involved in organoid formation we attempted to block this process by single cell suspensions of LIM 1863 reseeded in the presence of monoclonal antibodies. An anti-integrin antibody directed against a conformational epitope on the alpha v subunit totally inhibited organoid reformation. As a consequence of this inhibition of cell contact the colon carcinoma cells rapidly underwent apoptosis. Investigations of the apoptotic pathway involved suggested an induction mechanism since the onset of apoptosis in the contact- inhibited cells showed specific increased synthesis of 68- and 72-kD proteins. In addition, immunoblotting of cytosolic and nuclear extracts of the cells revealed the rapid translocation of the tumor suppressor gene product, p53 to the cell nucleus upon induction of apoptosis. These results suggest that cell-cell adhesion may be a vital regulator of colon development overcome in tumor cells by loss of adhesion molecules or of functional p53 protein. PMID:8163556

1994-01-01

326

Apoptosis in Leishmania species & its relevance to disease pathogenesis.  

PubMed

Apoptosis is a morphologically distinct form of cell death necessary for embryogenesis, tissue homeostasis and disease control in metazoans. Earlier, it was thought that apoptosis is the prerogative of multicellular organisms. However, it is now evident that unicellular organisms are also capable of undergoing apoptosis. In the context of Leishmania spp., a unicellular eukaryote responsible for causing leishmaniasis, the process of apoptosis is important for successful survival. The flagellated promastigote form of the parasite resides in the midgut of the insect vector, the female sandfly and at this niche; the cell fittest to survive to pass onto the pharynx of the fly is selected by eliminating unfit cells through apoptosis. Within the mammalian host, inside the macrophage, apoptosis is necessary to regulate cell numbers and to minimize immune reactions. With most apoptosis inducing stimuli, L. donovani shows typical features of apoptotic death like cell shrinkage, nuclear condensation and DNA fragmentation. Agents capable of precipitating apoptosis in this parasite include anti-leishmanial drugs like antimony, amphotericin B, pentamidine and miltefosine. Other agents like heat shock, treatment with staurosporine, knocking out centrin gene also precipitate apoptosis of the parasites. A pivotal role in cellular apoptosis is played by the single mitochondrion of Leishmania spp., where a fall or increase in mitochondrial potential leads to cell death by apoptosis. Ca2+ appears to be a vital ion involved in Leishmania apoptosis and partial inhibition of cytosolic Ca2+ increase achieved by chelating extracellular or intracellular Ca2+ during oxidative stress results in significant rescue of the fall of the mitochondrial membrane potential and consequently apoptosis. Elucidation of the molecular events linked to apoptotic death of Leishmania spp. might help define a more comprehensive view of the cell death machinery in terms of evolutionary origin and identify new target molecules for chemotherapeutic drug development and therapeutic intervention. PMID:16778307

Shaha, Chandrima

2006-03-01

327

High-throughput analytical techniques for multiresidue, multiclass determination of 653 pesticides and chemical pollutants in tea--Part III: Evaluation of the cleanup efficiency of an SPE cartridge newly developed for multiresidues in tea.  

PubMed

A comparative study was conducted over three stages on the cleanup efficiency of SPE cartridge Cleanert TPT, newly developed for multigroups of pesticide residues in tea. In Stage I, different SPE cartridges C18, graphite carbon black (GCB), primary secondary amine (PSA), and amino (NH2) were purchased and combined into 12 different sequences. Through the comparative test on cleanup efficiency of 84 representative pesticides in tea, Envi-Carb GCB + PSA with a good cleanup effect was selected. In Stage II, GC/MS test results from the comparative study of the extraction efficiency of 201 pesticides spiked into green tea and Woolong tea with Cleanert TPT and Envi-Carb + PSA SPE showed that average recoveries fell within 70-110% and RSD <20% for 193 and 184 pesticides, respectively, for green tea, accounting for 96.0 and 91.0% of the total number, respectively. GC/MS/MS test results also found 193 and 184 pesticides, respectively, meeting the recovery and RSD conditions, accounting for 96.0 and 91.5%, respectively, of the total number. For Woolong tea samples, GC/MS results showed that with Cleanert TPT and Envi-Carb + PSA SPE for cleanup, there were 192 and 177 pesticides, respectively, meeting the conditions, accounting for 95.5 and 88.1% of the total number, respectively. GC/MS/MS results demonstrated that there were 195 and 184 pesticides, respectively, meeting the conditions, accounting for 97.0 and 91.5% of the total number, respectively. It was seen that Cleanert TPT was superior to Envi-Carb + PSA in cleanup efficiency, whether for green or Woolong tea samples, or GC/MS or GC/MS/MS determination. In Stage III, 61104 results of the average content value of pesticides and RSD (two teas xtwo Youden pair concentrations x two kinds of SPE cartridges x two instruments x 19 tests x 201 pesticides) were derived from the 19 times stability tests over 3 months by paralleling three samples every 5 days via two instruments with two kinds of SPE cartridges for cleanup, respectively, against Youden Pair samples of the 201 incurred pesticides from green and Woolong teas. The statistical analysis found that detected values from the target pesticides of the incurred Youden pair samples showed no marked differences with cleanup by either Cleanert TPT or Envi-Carb + PSA, whether for green or Woolong tea, or G/IMS or G/IM/IMS. The test results using the two aforementioned kinds of SPE cleanup for above 93% pesticides had a tolerance less than 15%, which testifies that both cartridge cleanups met the requirement for pesticide residue analysis. PMID:24000765

Pang, Guo-Fang; Fan, Chun-Lin; Chang, Qiao-Ying; Li, Yan; Kang, Jian; Wang, Wen-Wen; Cao, Jing; Zhao, Yan-Bing; Li, Nan; Li, Zeng-Yin; Chen, Zong-Mao; Luo, Feng-Jian; Lou, Zheng-Yun

2013-01-01

328

Inhibitor of apoptosis proteins (IAPs) as regulatory factors of hepatic apoptosis.  

PubMed

IAPs are a group of regulatory proteins that are structurally related. Their conserved homologues have been identified in various organisms. In human, eight IAP members have been recognized based on baculoviral IAP repeat (BIR) domains. IAPs are key regulators of apoptosis, cytokinesis and signal transduction. The antiapoptotic property of IAPs depends on their professional role for caspases. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. IAPs impede apoptotic process via membrane receptor-dependent (extrinsic) cascade and mitochondrial dependent (intrinsic) pathway. IAP-mediated apoptosis affects the progression of liver diseases. Therapeutic options of liver diseases may depend on the understanding toward mechanisms of the IAP-mediated apoptosis. PMID:23770286

Wang, Kewei; Lin, Bingliang

2013-10-01

329

The actin cytoskeleton as a sensor and mediator of apoptosis  

PubMed Central

Apoptosis is an important biological process required for the removal of unwanted or damaged cells. Mounting evidence implicates the actin cytoskeleton as both a sensor and mediator of apoptosis. Studies also suggest that actin binding proteins (ABPs) significantly contribute to apoptosis and that actin dynamics play a key role in regulating apoptosis signaling. Changes in the organization of the actin cytoskeleton has been attributed to the process of malignant transformation and it is hypothesized that remodeling of the actin cytoskeleton may enable tumor cells to evade normal apoptotic signaling. This review aims to illuminate the role of the actin cytoskeleton in apoptosis by systematically analyzing how actin and ABPs regulate different apoptosis pathways and to also highlight the potential for developing novel compounds that target tumor-specific actin filaments. PMID:22880146

Desouza, Melissa; Gunning, Peter W.; Stehn, Justine R.

2012-01-01

330

Self-consumption: the interplay of autophagy and apoptosis  

PubMed Central

Autophagy and apoptosis control the turnover of organelles and proteins within cells, and of cells within organisms, respectively, and many stress pathways sequentially elicit autophagy, and apoptosis within the same cell. Generally autophagy blocks the induction of apoptosis, and apoptosis-associated caspase activation shuts off the autophagic process. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis or necrosis, and autophagy has been shown to degrade the cytoplasm excessively, leading to ‘autophagic cell death’. The dialogue between autophagy and cell death pathways influences the normal clearance of dying cells, as well as immune recognition of dead cell antigens. Therefore, the disruption of the relationship between autophagy and apoptosis has important pathophysiological consequences. PMID:24401948

Marino, Guillermo; Niso-Santano, Mireia; Baehrecke, Eric H.; Kroemer, Guido

2014-01-01

331

Does atorvastatin induce aortic smooth muscle cell apoptosis in vivo?  

Microsoft Academic Search

It has been reported that HMG-CoA reductase inhibitors such as atorvastatin induce vascular smooth muscle cell (SMC) apoptosis in vitro. However, this effect remains to be demonstrated in vivo. The present studies were designed to test the ability of atorvastatin to induce SMC apoptosis in vivo, using the spontaneously hypertensive rat (SHR) as a well-known reference model of SMC apoptosis

Marielle Doyon; Taben Mary Hale; Julie-Emilie Huot-Marchand; Rong Wu; Jacques de Champlain; Denis deBlois

2011-01-01

332

Prevention of Photoreceptor Apoptosis by Activation of the Glucocorticoid Receptor  

Microsoft Academic Search

PURPOSE. Evidence has accumulated that excessive light expo- sure may promote age-related and inherited retinal degenera- tion, in which photoreceptor death by apoptosis leads to loss of vision. In the current study, the effect of elevated cortico- steroid levels on light-induced apoptosis of photoreceptors was determined. METHODS. Photoreceptor apoptosis was induced in retinas of BALB\\/c mice by exposure to diffuse

Andreas Wenzel; Christian Grimm; Mathias W. Seeliger; Gesine Jaissle; Farhad Hafezi; Robert Kretschmer; Eberhart Zrenner; Charlotte E. Reme

2001-01-01

333

Dendritic Cell Apoptosis in the Maintenance of Immune Tolerance  

Microsoft Academic Search

Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective

Min Chen; Yui-Hsi Wang; Yihong Wang; Li Huang; Hector Sandoval; Yong-Jun Liu; Jin Wang

2006-01-01

334

Downregulation of Apoptosis-Related Genes in Keloid Tissues  

Microsoft Academic Search

Background. Physiologically programmed cell death or apoptosis occurs during the natural balance between cellular proliferation and demise.Materials and Methods. We compared the expression of 64 apoptosis-related genes in keloids and normal scars to investigate the potential role of apoptosis in keloid formation. Two sets of mRNA were isolated from keloids excised from four previously untreated patients and four normal scar

David N. Sayah; Chia Soo; William W. Shaw; James Watson; Diana Messadi; Michael T. Longaker; Xinli Zhang; Kang Ting

1999-01-01

335

Ebselen inhibition of apoptosis by reduction of peroxides  

Microsoft Academic Search

We investigated the capacity of ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], a glutathione peroxidase mimic, to protect cells from radiation-induced apoptosis. Incubating mouse thymocytes with 25 ?M ebselen immediately after 60Co gamma-radiation exposure (5 Gy) inhibited morphological changes associated with apoptosis. Treatment of thymocytes with ebselen before, during, or after irradiation completely blocked internucleosomal DNA fragmentation, a biochemical marker for apoptosis. We measured peroxides

Narayani Ramakrishnan; John F. Kalinich; David E. McClain

1996-01-01

336

[Changes of trace elements in cells of lung cancer and cervix cancer before apoptosis and after apoptosis].  

PubMed

The sensitivity of total reflection X-ray fluorescence analysis (TXRF) is higher than normal X-ray fluorescence analysis (XRF). The cells of lung cancer and cervix cancer were researched before apoptosis and after apoptosis employed the method of TXRF on new transformed synchrotron radiation XRF experimental station of new 3W1A beam line which built on Beijing Synchrotron Radiation Facility (BSRF) of BEPC (new detector and spectrometer systems). We acquired their fluorescence spectrum of various elements before apoptosis and after apoptosis. We discovered there were interesting results that changes even remarkable changes of some elemental contents had occurred in these cells before apoptosis and after apoptosis. These alterations of elemental contents have served an inspiration for us: if their regularities of change are found, we will hope that some contributions would be done at the treatments of cancer. PMID:12953498

Li, G; Wu, Y; Huang, Y; Zhao, L; Li, J; Zhang, T; Cao, E

2000-04-01

337

Cucurbitacin B inhibits growth and induces apoptosis through the JAK2/STAT3 and MAPK pathways in SH?SY5Y human neuroblastoma cells.  

PubMed

Cucurbitacin B (CuB) is a tetracyclic triterpene that is contained in extracts from cucurbitaceous plants and has been demonstrated to have anticancer and anti?in?ammatory activities. The purpose of the present study was to determine whether CuB exhibits anticancer effects on SH?SY5Y human neuroblastoma cells and to analyze the underlying molecular mechanism. The results demonstrated that CuB not only induced cell cycle arrest at the G2/M phase, but also induced apoptosis as characterized by positive Annexin V staining, downregulation of phospho?Janus kinase 2 (p?JAK2), phospho?signal transducer and activator of transcription 3 (p?STAT3), phospho?extracellular signal?regulated kinases and the activation of c?Jun N?terminal kinase and p38 mitogen activated protein kinase (MAPK). CuB also altered the expression of gene products that mediated cell proliferation (Cyclin B1 and cyclin?dependent kinase 1), cell survival (B?cell lymphoma 2, Bcl2?associated X protein) and increased the expression of p53 and p21. These results provide the evidence that JAK2/STAT3 and MAPKs have crucial roles in CuB?induced growth inhibition and apoptosis in SH?SY5Y human neuroblastoma cells. PMID:24789581

Zheng, Qian; Liu, Yunyi; Liu, Weiwei; Ma, Fengyun; Zhou, Yi; Chen, Mingjie; Chang, Junli; Wang, Yuesheng; Yang, Guangxiao; He, Guangyuan

2014-07-01

338

Evolutionary conservation of apoptosis mechanisms: Lepidopteran and baculoviral inhibitor of apoptosis  

E-print Network

, Guy S. Salvesen , Henning R. Stennicke , Bruce D. Hammock , and John C. Reed§ *Microbiology Program of the functions of IAPs and their inhibitors. Caspases are a family of intracellular proteases responsible of the Orthopoxvirus family cowpox virus (4). Inhibitor of apoptosis protein (IAP) family proteins were first

Hammock, Bruce D.

339

Measuring and Modeling Apoptosis in Single Cells  

PubMed Central

Cell death plays an essential role in the development of tissues and organisms, the etiology of disease, and the responses of cells to therapeutic drugs. Here we review progress made over the last decade in using mathematical models and quantitative, often single-cell, data to study apoptosis. We discuss the delay that follows exposure of cells to prodeath stimuli, control of mitochondrial outer membrane permeabilization, switch-like activation of effector caspases, and variability in the timing and probability of death from one cell to the next. Finally, we discuss challenges facing the fields of biochemical modeling and systems pharmacology. PMID:21414484

Spencer, Sabrina L.; Sorger, Peter K.

2011-01-01

340

An increase of granulosa cell apoptosis mediates aqueous neem (Azadirachta indica) leaf extract-induced oocyte apoptosis in rat  

PubMed Central

Objective: Neem plant (Azadirachta indica) has been extensively used in Ayurvedic system of medicine for female fertility regulation for a long time, but its mechanism of action remains poorly understood. Hence, the present study was aimed to determine whether an increase of granulosa cell apoptosis is associated with aqueous neem leaf extract (NLE)-induced oocyte apoptosis. Materials and Methods: Sexually immature female rats of 20 days old were fed NLE (50 mg/day) for 10 days and then subjected to superovulation induction protocol. The morphological changes in cumulus oocyte complexes (COCs), rate of oocyte apoptosis, hydrogen peroxide (H2O2), total nitrite, and cytochrome c concentrations, inducible nitric oxide synthase (iNOS), cytochrome c, p53, Bcl2 and Bax expressions, deoxyribonucleic acid (DNA) fragmentation, and estradiol 17? level in granulosa cells collected from preovulatory COCs were analyzed. Results: Aqueous NLE increased H2O2 concentration and decreased catalase activity, increased iNOS expression and total nitrite concentration, increased p53, Bax, and p53 expressions but decreased Bcl2 expression, increased cytochrome c concentration and induced DNA fragmentation in granulosa cells. An increased granulosa cell apoptosis resulted in reduced estradiol 17? concentration and induced apoptosis in ovulated oocytes. Conclusion: We conclude that aqueous NLE-induced granulosa cell apoptosis through the mitochondria-mediated pathway, reduced estradiol 17? concentration and induced apoptosis in ovulated oocytes. Thus, granulosa cell apoptosis mediates NLE-induced oocyte apoptosis during female fertility regulation in rat. PMID:23776837

Tripathi, Anima; Shrivastav, Tulsidas G; Chaube, Shail K

2013-01-01

341

Tumor Necrosis Factor ?-induced Inflammation Is Increased but Apoptosis Is Inhibited by Common Food Additive Carrageenan*  

PubMed Central

Tumor necrosis factor (TNF)-?, a homotrimeric, pleiotropic cytokine, is secreted in response to inflammatory stimuli in diseases such as rheumatoid arthritis and inflammatory bowel disease. TNF-? mediates both apoptosis and inflammation, stimulating an inflammatory cascade through the non-canonical pathway of NF-?B activation, leading to increased nuclear RelB and p52. In contrast, the common food additive carrageenan (CGN) stimulates inflammation through both the canonical and non-canonical pathways of NF-?B activation and utilizes the adaptor molecule BCL10 (B-cell leukemia/lymphoma 10). In a series of experiments, colonic epithelial cells and mouse embryonic fibroblasts were treated with TNF-? and carrageenan in order to simulate the possible effects of exposure to dietary CGN in the setting of a TNF-?-mediated inflammatory disease process. A marked increase in secretion of IL-8 occurred, attributable to synergistic effects on phosphorylated NF-?B-inducing kinase (NIK) in the non-canonical pathway. TNF-? induced the ubiquitination of TRAF2 (TNF receptor-associated factor 2), which interacts with NIK, and CGN induced phosphorylation of BCL10, leading to increased NIK phosphorylation. These results suggest that TNF-? and CGN in combination act to increase NIK phosphorylation, thereby increasing activation of the non-canonical pathway of NF-?B activation. In contrast, the apoptotic effects of TNF-?, including activation of caspase-8 and PARP-1 (poly(ADP-ribose) polymerase 1) fragmentation, were markedly reduced in the presence of CGN, and CGN caused reduced expression of Fas. These findings demonstrate that exposure to CGN drives TNF-?-stimulated cells toward inflammation rather than toward apoptotic cell death and suggest that CGN exposure may compromise the effectiveness of anti-TNF-? therapy. PMID:20937806

Bhattacharyya, Sumit; Dudeja, Pradeep K.; Tobacman, Joanne K.

2010-01-01

342

TNF and suppression of hepatocyte apoptosis Tumour necrosis factor (TNF): role in  

E-print Network

TNF and suppression of hepatocyte apoptosis Tumour necrosis factor (TNF): role in suppression Running title: TNF and suppression of hepatocyte apoptosis Abbreviations: ARPP: acidic ribophosphoprotein2: TNF receptor 2 #12;TNF and suppression of hepatocyte apoptosis Abstract The peroxisome

Omiecinski, Curtis

343

Herpes Simplex Virus Type 1 Renders Infected Cells Resistant to Cytotoxic T-Lymphocyte-Induced Apoptosis  

Microsoft Academic Search

Many viruses interfere with apoptosis of infected cells, presumably preventing cellular apoptosis as a direct response to viral infection. Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as part of the \\

KEITH R. JEROME; JONATHAN F. TAIT; DAVID M. KOELLE; LAWRENCE COREY

1998-01-01

344

Simultaneous analysis of psychotropic phenylalkylamines in oral fluid by GC-MS with automated SPE and its application to legal cases.  

PubMed

Phenylalkylamine derivatives, such as methamphetamine (MA), amphetamine (AM), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), phentermine (PT), fenfluramine (FFA) and phenmetrazine (PM), and ketamine (KT) are widely abused recreational or anorectic drugs in Korea and are regulated under the Controlled Substance Act in Korea. Phenylalkylamines and ketamine analysis is normally performed using both urine and hair samples but there is no established method for the simultaneous analysis of all these phenylalkylamines and ketamine in oral fluids. Oral fluid is easy to collect/handle and can provide an indication of recent drug abuse. In this study, to confirm the presence of phenylalkylamine derivatives and ketamine in oral fluid after screening with an immunoassay, an analytical method using automated solid phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) was developed and fully validated according to international guidelines. The applicability of the assay was demonstrated by analyzing of authentic oral fluid samples and the results of oral fluid analysis were compared with those in urine and hair to to evaluate the feasibility of oral fluid in forensic cases. The recovery of phenylalkylamines and ketamine from oral fluid collection devices was also assessed. Oral fluid specimens from 23 drug abuse suspects submitted by the police were collected using Salivette (Sarstedt, Nümbrecht, Germany), Quantisal (Immunalysis, Pomona, CA) or direct expectoration. The samples were screened using a biochip array analyzer (Evidence Investigator, Randox, Antrim, UK). For confirmation, the samples were analyzed by GC-MS in selected-ion monitoring (SIM) mode after extraction using automated SPE (RapidTrace, Zymark, MA, USA) with a mixed-mode cation exchange cartridge (CLEAN SCREEN, 130 mg/3 ml, UCT, PA, USA) and derivatization with trifluoroacetic anhydride (TFA). The results from the immunoassay were consistent with those from GC-MS. Twenty oral fluid samples gave positive results for MA, AM, PT and/or PM among the 23 cases, which gave positive results in urine and/or hair. Although large variations in the MA, AM, PT and PM concentrations were observed in three different specimens, the oral fluid specimen was useful for demonstrating phenylalkylamines and ketamine abuse as an alternative specimen for urine. PMID:21377815

Choi, Hyeyoung; Baeck, Seungkyung; Jang, Moonhee; Lee, Sooyeun; Choi, Hwakyung; Chung, Heesun

2012-02-10

345

Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria.  

PubMed

Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti?inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF?7 and MDA?MB?231. MCF?7 is p53 pro?cient (p53+/+) and MDA?MB?231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase?3 activity. Reverse transcription?polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53?upregulated modulator of apoptosis (PUMA), Bax and Bcl?2. Finally, the affect of Tau on the growth of MDA?MB?231?cell?nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration? and time?dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up? and downregulated the expression of Bax and Bcl?2 protein, giving rise to increased activation of caspase?3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status. PMID:25395275

Zhang, Xiali; Lu, Hongfei; Wang, Yibing; Liu, Chunju; Zhu, Weifeng; Zheng, Shuangyan; Wan, Fusheng

2015-01-01

346

Cadmium Increases Human Fetal Germ Cell Apoptosis  

PubMed Central

Background Cadmium (Cd) is a common environmental pollutant and a major constituent of tobacco smoke. Adverse effects of this heavy metal on reproductive function have been identified in adults; however, no studies have examined its effects on human reproductive organs during development. Objectives Using our previously developed organ culture system, we investigated the effects of cadmium chloride on human gonads at the beginning of fetal life, a critical stage in the development of reproductive function. Methods Human fetal gonads were recovered during the first trimester (7–11 weeks postconception) and cultured with or without Cd. We used different concentrations of Cd and compared results with those obtained with mouse fetal gonads at similar stages. Results Cd, at concentrations as low as 1 ?M, significantly decreased the germ cell density in human fetal ovaries. This correlated with an increase in germ cell apoptosis, but there was no effect on proliferation. Similarly, in the human fetal testis, Cd (1 ?M) reduced germ cell number without affecting testosterone secretion. In mouse fetal gonads, Cd increased only female germ cell apoptosis. Conclusions This is the first experimental demonstration that Cd, at low concentrations, alters the survival of male and female germ cells in humans. Considering data demonstrating extensive human exposure, we believe that current environmental levels of Cd could be deleterious to early gametogenesis. PMID:20064782

Angenard, Gaelle; Muczynski, Vincent; Coffigny, Herve; Pairault, Catherine; Duquenne, Clotilde; Frydman, Rene; Habert, Rene; Rouiller-Fabre, Virginie; Livera, Gabriel

2010-01-01

347

Apoptosis: Calling Time on Apoptosome Activity  

NSDL National Science Digital Library

Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a “molecular timer” that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may enable cells to prevent low amounts of apoptosome activation from spiraling out of control unless sufficient numbers of apoptosomes are assembled within a particular time window, which would drive full-blown caspase activation and apoptosis.

Colin Adrain (Cambridge;Medical Research Council Laboratory of Molecular Biology REV); Seamus J. Martin (Ireland.;Trinity College REV)

2009-10-06

348

Opium Induces Apoptosis in Jurkat Cells  

PubMed Central

Background The direct effect of some opioids on immune cells has been demonstrated. The aim of this study was to assess the apoptotic effect of opium on Jurkat T lymphocyte cells. Methods Different concentrations of opium (2.86 × 10-3 to 2.86 × 10-11 g/ml) were added to 24-well plates containing 5 × 105 Jurkat cells. Apoptotic events were assessed after 6, 24, and 72 hours by flow-cytometric detection of surface phosphatidylserine. Findings Significant differences in apoptosis of Jurkat cells were seen at 24 and 72 hours in different concentrations of opium (P < 0.05). After 72 hours, significant increase in necrosis of Jurkat cells was seen in opium concentration of 2.85 × 10-3 g/ml compared to cells without opium (control) (P < 0.05). Conclusion These results showed that opium directly increases apoptosis and necrosis of T lymphocytes. This effect may play a role in immune dysfunction in opium addicts. PMID:24494155

Igder, Somayeh; Asadikaram, Gholam Reza; Sheykholeslam, Farzaneh; Sayadi, Ahmad Reza; Mahmoodi, Mehdi; Kazemi Arababadi, Mohammad; Rasaee, Mohammad Javad

2013-01-01

349

Relevance of apoptosis in influencing recovery of hibernating myocardium  

Microsoft Academic Search

Background: Hibernating myocardium (HM) is viable but dysfunctional myocardium which can recover following revascularization. Myocyte necrosis is virtually absent in HM; however, cellular loss may take place by apoptosis, although this is controversial. Aim: To assess the presence of apoptosis and its relevance in HM. Methods: During coronary artery by-pass surgery (CABG), 21 patients underwent transmural biopsy in the dysfunctional

Annalisa Angelini; Giuseppe Maiolino; Giovanni La Canna; Claudio Ceconi; Fiorella Calabrese; Elena Pettenazzo; Marialuisa Valente; Ottavio Alfieri; Gaetano Thiene; Roberto Ferrari

2007-01-01

350

RESEARCH Open Access Hyperglycaemia and apoptosis of microglial cells  

E-print Network

correlated with the duration of septic shock, nor with GLUT4 and 5 expression. Neuronal apoptosis ischaemia, neuronal and microglial apoptosis, neuronal Glucose Transporter (GLUT) 4, endothelial inducible Nitric Oxide Synthase (iNOS), microglial GLUT5 expression, microglial and astrocyte activation. Blood

Paris-Sud XI, Université de

351

Serial killers: ordering caspase activation events in apoptosis  

Microsoft Academic Search

Caspases participate in the molecular control of apoptosis in several guises; as triggers of the death machinery, as regulatory elements within it, and ultimately as a subset of the effector elements of the machinery itself. The mammalian caspase family is steadily growing and currently contains 14 members. At present, it is unclear whether all of these proteases participate in apoptosis.

EA Slee; C Adrain; SJ Martin

1999-01-01

352

Apoptosis and Post-infarction Left Ventricular Remodeling  

Microsoft Academic Search

Apoptosis is a common pathological feature in acute myocardial infarction (AMI), however, its role in the later phases (>10 days) of AMI and in post-infarction left ventricular remodeling has not been characterized. The aim of the study was to identify signs of ongoing cell apoptosis late post AMI. Sixteen hearts were collected at autopsy from subjects 12 to 62 days

Alfonso Baldi; Antonio Abbate; Rossana Bussani; Giuseppe Patti; Rosetta Melfi; Anna Angelini; Aldo Dobrina; Raffaele Rossiello; Furio Silvestri; Feliciano Baldi; Germano Di Sciascio

2002-01-01

353

Diagnosing and exploiting cancer's addiction to blocks in apoptosis  

Microsoft Academic Search

Cancer cells survive despite violating rules of normal cellular behaviour that ordinarily provoke apoptosis. The blocks in apoptosis that keep cancer cells alive are therefore attractive candidates for targeted therapies. Recent studies have significantly increased our understanding of how interactions among proteins in the BCL2 family determine cell survival or death. It is now possible to systematically determine how individual

Anthony G. Letai

2008-01-01

354

Apoptosis in the lung: induction, clearance and detection  

Microsoft Academic Search

Apoptosis and other forms of programmed cell death are important contributors to lung pathophysiology. In this brief review we discuss some of the implications of finding apoptotic cells in the lung and methods for their detection. The balance between induction of apoptosis and the normally highly efficient clearance of such cells shows that these are highly dynamic processes and suggests

P. M. Henson; R. M. Tuder

2008-01-01

355

Apoptosis and cancer: the genesis of a research field  

Microsoft Academic Search

In multicellular organisms, the total number of cells is a balance between the cell-generating effects of mitosis and cell death that is induced through apoptosis. A disruption of this delicate balance can lead to the development of cancer. This Timeline article focuses on how the field of apoptosis biology has developed in the context of its contribution to our understanding

Thomas G. Cotter

2009-01-01

356

Ecdysone signaling at metamorphosis triggers apoptosis of Drosophila abdominal muscles  

E-print Network

Ecdysone signaling at metamorphosis triggers apoptosis of Drosophila abdominal muscles Jonathan KeywordsQ3 : Metamorphosis Muscle Drosophila Histolysis Apoptosis Autophagy Ecdysone Ftz-f1 a b s t r a c t One of the most dramatic examples of programmed cell death occurs during Drosophila metamorphosis

Perrimon, Norbert

357

Delay of neutrophil apoptosis in acute coronary syndromes  

Microsoft Academic Search

Apoptosis of polymorphonuclear neu- trophils (PMN) is currently discussed as a key event in the control of inflammation. This study deter- mined PMN apoptosis and its underlying mecha- nisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 sub- jects of each C, SAP, UAP, and AMI.

C. D. Garlichs; S. Eskafi; I. Cicha; A. Schmeisser; B. Walzog; D. Raaz; C. Stumpf; A. Yilmaz; J. Bremer; J. Ludwig; W. G. Daniel

2003-01-01

358

Mitochondrion-mediated apoptosis induced by photofrin-PDT  

NASA Astrophysics Data System (ADS)

Apoptosis is an important cellular event that plays a key role in pathogeny and therapy of many diseases. The mechanisms of the initiation and regulation of PDT-induced apoptosis are complex. Some PDT-associated apoptosis pathways involved plasma membrane death receptors, mitochondria, lysosomes and endoplasmic reticulum (ER). In order to determine the apoptosis pathway induced by Photofrin-PDT, we used fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to monitor the dynamics of caspase-3 activation after PDT treatment and also measured caspase-8 activity. With laser scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes after PDT treatment. This was followed by mitochondrial membrane potential (??m), cytochrome c release, caspase-9 activity, caspase-3 activity and apoptosis. After PDT treatment, caspase-3 was activated rapidly while caspase-8 remained inactivated. Our results indicated that PDT-induced apoptosis was initiated from mitochondria pathway and independent of caspase-8 activation. The activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. PDT-induced apoptosis is directly initiated from mitochondria pathway and not involved in the death receptors-dependent pathway. Our results demonstrated that FRET could be an effective tool to determine PDT-induced apoptosis and other cell death mechanism.

Wu, Yunxia; Xing, Da

2007-05-01

359

Antioxidants Prevent Ethanol-Associated Apoptosis in Fetal Rhombencephalic Neurons  

PubMed Central

It is well known that ethanol damages the developing nervous system by augmenting apoptosis. Previously, this laboratory reported that ethanol augments apoptosis in fetal rhombencephalic neurons, and that the increased apoptosis is associated with reduced activity of the phosphatidylinositol 3’kinase pathway and downstream expression of pro-survival genes. Other laboratories have shown that another mechanism by which ethanol induces apoptosis in developing neurons is through the generation of reactive oxygen species (ROS) and the associated oxidative stress. The present study used an in vitro model to investigate the potential neuroprotective effects of several antioxidants against ethanol-associated apoptosis in fetal rhombencephalic neurons. The investigated antioxidants included three phenolics: (-)-epigallocatechin-3-gallate (EGCG), a flavanoid polyphenol found in green tea; curcumin, found in tumeric; and resveratrol (3,5,4’-trihydroxystilbene), a component of red wine. Additional antioxidants, including melatonin, a naturally occurring indole, and ?-lipoic acid, a naturally occurring dithiol, were also investigated. These studies demonstrated that a 24-hour treatment of fetal rhombencephalic neurons with 75 mM ethanol caused a 3-fold increase in the percentage of apoptotic neurons. However, co-treatment of these cultures with any of the five different antioxidants prevented ethanol-associated apoptosis. Antioxidant treatment did not alter the extent of apoptosis in control neurons, i.e., those cultured in the absence of ethanol. These studies showed that several classes of antioxidants can exert neuroprotection against ethanol-associated apoptosis in fetal rhombencephalic neurons. PMID:18329634

Antonio, Angeline M.; Druse, Mary J.

2008-01-01

360

Chapter Six Analyzing Lipid Raft Dynamics during Cell Apoptosis  

Microsoft Academic Search

Increasing lines of evidence suggest a role for lipid rafts, glycosphingolipid?enriched microdomains, in cell life and death. This chapter describes in brief the methods used to analyze raft interactions with proteins involved in apoptosis. This chapter focuses mainly on coimmunoprecipitation methods, which represent a useful tool in analyzing raft dynamics during apoptosis. Glycosphingolipid analysis in the immunoprecipitates is performed by

Walter Malorni; Tina Garofalo; Antonella Tinari; Valeria Manganelli; Roberta Misasi; Maurizio Sorice

2008-01-01

361

Stearate Preferentially Induces Apoptosis in Human Breast Cancer Cells  

PubMed Central

Stearic acid (stearate) is an 18-carbon saturated fatty acid that has been shown to inhibit invasion and proliferation and induce apoptosis in various human cell types. The specificity of stearate-induced apoptosis for cancerous versus non-cancerous breast cells has not been examined and the mechanism underlying stearate-induced apoptosis is unknown. Morphological analysis, cell viability and caspase-3 activity assays demonstrated that stearate activated apoptosis preferentially in cancerous breast cells in a time and dose dependent manner. Inhibition of de novo diacylgycerol synthesis or protein kinase C (PKC) blocked stearate-induced caspase-3 activity, indicating the involvement of a novel or classical PKC isozyme. To our knowledge this is the first study showing that stearate induces apoptosis preferentially in breast cancer cells and implicates protein kinase C in the signaling cascade. These results raise the possibility of dietary stearate having a beneficial role in the prevention or treatment of breast cancer. PMID:19838949

Evans, Lynda M.; Cowey, Stephanie L.; Siegal, Gene P.; Hardy, Robert W.

2010-01-01

362

Simultaneous determination of 30 hormones illegally added to anti-ageing functional foods using UPLC-MS/MS coupled with SPE clean-up.  

PubMed

A novel analytical method employing solid-phase extraction (SPE) coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 30 hormones in anti-ageing functional foods (capsules, powders and tablets). The analytes were extracted with acetic acid-acetonitrile (1-99 v/v), methanol and acetone, respectively. The extract was purified using a combined column, followed by analyte detection with electrospray ionisation in positive- or negative-ion modes. The results indicated that the 30 compounds had good linear correlations in the range of 1-1000 ?g kg(-1), and the correlation coefficients were above 0.99. The limits of detection (LOD) and limits of quantification (LOQ) were 0.03-2 and 0.1-5 ?g kg(-1), respectively. The average recovery of 30 compounds at the three spiked levels varied from 74.7% to 124.1%, and the relative standard deviation (RSD) was 2.4-15.0%. This method was applied to the analysis of hormones in 14 real samples of which seven hormones (such as estrone, dienestrol) were detected in four samples, but the remainder of the hormones were not detected. The developed method is sensitive, efficient, reliable and applicable to real samples. PMID:25188907

He, Xiaoqin; Xi, Cunxian; Tang, Bobin; Wang, Guomin; Chen, Dongdong; Peng, Tao; Mu, Zhaode

2014-10-01

363

Optimization and validation of a simple and fast method for the determination of fungicides in must and wine samples by SPE and GC/MS.  

PubMed

A rapid, simple, and low-cost method based on SPE was optimized and validated for simultaneous determination of eight fungicides belonging to different chemical classes in must and wine. The method involves extraction of 10 mL of must or wine samples with a C18 cartridge using 5 mL of dichloromethane as the elution solvent. Separation and final determination of the fungicides (vinclozolin, dichlofluanid, penconazol, captan, quinoxyfen, fluquinconazol, boscalid, and pyraclostrobin) was performed by GC coupled to single quadrupole MS. Recoveries at 10, 50, and 100 microg/L were between 71 and 106% in both matrixes for the fungicides evaluated. The calculated LOQ ranged from 1.5 to 3.4 microg/L in must and 1.1 to 3.8 microg/L in wine. Matrix effects observed for wine and must samples were overcome by using matrix-matched calibration. The developed method was linear at concentrations within the tested interval, with coefficients of determination higher than 0.999. The expanded uncertainties at 10 microg/L were <20% for all analytes. Intralaboratory precision in terms of the Horwitz ratio of the fungicides evaluated was below 0.5, suggesting the ruggedness of the method. The proposed method was applied to determine fungicide residues in must samples obtained from red grapes treated with two new commercial formulations, as well as in their corresponding final wines. PMID:23175987

Lagunas-Allué, Laura; Sanz-Asensio, Jesús; Martínez-Soria, Maria-Teresa

2012-01-01

364

An update for human blood plasma pretreatment for optimized recovery of low-molecular-mass peptides prior to CE–MS and SPE–CE–MS.  

PubMed

Protein precipitation and centrifugal filtration are well-established methods for concentrating and purifying peptides with a low relative molecular mass (Mr) from human blood plasma before proteomic and peptidomic studies using high-performance separation techniques, but there is little information on peptide recoveries. Here, we evaluate acetonitrile precipitation followed by a range of centrifugal filtration conditions for the analysis of low Mr peptides in human blood plasma before CE–MS and SPE coupled online to CE–MS. Three opioid peptides were used as model compounds, that is, dynorphin A 1–7, endomorphin 1, and methionine enkephalin and 3, 10, and 30 K Mr cut-off cellulose acetate filters (Amicon® Ultra-0.5) and 10 K Mr cut-off polyethersulfone filters (Vivaspin® 500) were studied. Unexpectedly, recoveries and repeatability were only optimum after passivating the 10 K Mr cut-off cellulose acetate filters with PEG to avoid peptide adsorption on the inner walls of the plastic sample reservoir. PMID:24151123

Pont, Laura; Benavente, Fernando; Barbosa, José; Sanz-Nebot, Victoria

2013-12-01

365

SpeX Spectroscopy of Unresolved Very Low Mass Binaries. II. Identification of 14 Candidate Binaries with Late-M/Early-L and T Dwarf Components  

NASA Astrophysics Data System (ADS)

Multiplicity is a key statistic for understanding the formation of very low mass (VLM) stars and brown dwarfs. Currently, the separation distribution of VLM binaries remains poorly constrained at small separations (<=1 AU), leading to uncertainty in the overall binary fraction. We approach this problem by searching for late-M/early-L plus T dwarf spectral binaries whose combined light spectra exhibit distinct peculiarities, allowing for separation-independent identification. We define a set of spectral indices designed to identify these systems, and we use a spectral template fitting method to confirm and characterize spectral binary candidates from a library of 815 spectra from the SpeX Prism Spectral Libraries. We present 11 new binary candidates, confirm 3 previously reported candidates, and rule out 2 previously identified candidates, all with primary and secondary spectral types in the range M7-L7 and T1-T8, respectively. We find that subdwarfs and blue L dwarfs are the primary contaminants in our sample and propose a method for segregating these sources. If confirmed by follow-up observations, these systems may add to the growing list of tight separation binaries, whose orbital properties may yield further insight into brown dwarf formation scenarios.

Bardalez Gagliuffi, Daniella C.; Burgasser, Adam J.; Gelino, Christopher R.; Looper, Dagny L.; Nicholls, Christine P.; Schmidt, Sarah J.; Cruz, Kelle; West, Andrew A.; Gizis, John E.; Metchev, Stanimir

2014-10-01

366

Polychlorinated biphenyls (PCBs) detection in milk samples by an electrochemical magneto-immunosensor (EMI) coupled to solid-phase extraction (SPE) and disposable low-density arrays.  

PubMed

An electrochemical immunosensor for polychlorinated biphenyl (PCB) detection based on graphite screen-printed low-density arrays and on magnetic beads is reported. The immunological reaction for the detection of PCBs is based on a direct competitive assay using alkaline phosphatase (AP) as enzymatic label. After the immunochemical recognition, the modified magnetic beads are captured by a magnet on the surface of the graphite working electrode. The electrochemical detection is thus achieved through the addition of the AP substrate (alpha-naphthyl-phosphate). Two different antibodies (sIgG anti-PCB28 and rIgG anti-PCB77) were tested and compared in terms of sensitivity and ability to recognise different congeners. The developed electrochemical magneto-immunosensor (EMI) was successfully combined with solid-phase extraction (SPE) for the analysis of PCBs in milk samples. In spiked samples a recovery of 80% was obtained. The proposed strategy offers great promise for rapid, simple, cost-effective, and on-site analysis of clinical, food and environmental samples, considering also that low-density arrays allow the simultaneous analysis of different processed samples. PMID:17560379

Centi, S; Silva, E; Laschi, S; Palchetti, I; Mascini, M

2007-06-26

367

Transcription abnormalities potentiate apoptosis of normal human fibroblasts.  

PubMed Central

BACKGROUND: Apoptosis is a natural process by which damaged and potentially tumorigenic cells are removed. Induction of apoptosis is important in chemotherapy aimed at eliminating cancer cells. We address the mechanisms by which this process can be triggered in cells that are recalcitrant to cell death induced by DNA-damaging agents. MATERIALS AND METHODS: Normal human fibroblasts and lymphoblasts, and fibroblasts with defined genetic changes, were treated with DNA-damaging agents and inhibitors of transcription. Western blotting was used to study the expression of some of the key factors involved in the response to DNA damage and the induction of apoptosis, namely, p53, p21WAFI,Cip1, Mdm2, Bax, and CD95 (Fas/APO1). Apoptosis was followed by various criteria, including DNA fragmentation, specific proteolysis, cell morphology, viability, and FACS scan for sub-G1 cells. RESULTS: Normal human fibroblasts were more resistant than lymphoblasts to DNA damage-induced apoptosis. The DNA-damaging agents mitomycin C and cisplatin induced rapid apoptosis of fibroblasts with defects in the repair of transcribed DNA, compared with wild-type cells or those with defects in overall genome repair. Short-term treatment with inhibitors of RNA polymerase II transcription, actinomycin D, and alpha-amanitin induced rapid cell death of normal fibroblasts. These results show that there is a link between defective transcription and apoptosis. Treatments and genetic backgrounds that favored apoptosis were associated with efficient and prolonged induction of p53 and often altered or imbalanced expression of its downstream effectors p21WAFI,Cip1 and Mdm2, whereas there were no changes in Bax or CD95 (Fas/APO1). CONCLUSION: Transcription inhibitors increase p53 levels and are better inducers of apoptosis than DNA-damaging agents in some cell types. Apoptosis might be triggered by blocked polymerases and/or faulty expression of downstream effectors. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:9440118

Andera, L.; Wasylyk, B.

1997-01-01

368

NF-?B Inducing Kinase, a Central Signaling Component of the Non-Canonical Pathway of NF-?B, Contributes to Ovarian Cancer Progression  

PubMed Central

Ovarian cancer is one of the leading causes of female death and the development of novel therapeutic approaches is urgently required. Nuclear factor-?B (NF-?B) is constitutively activated in several types of cancer including ovarian cancer and is known to support the survival of cancer cells. However, molecular mechanisms of persistent activation of NF-?B in ovarian cancer remain largely unknown. We report here that, in addition to the previously reported canonical activation, NF-?B is activated through the noncanonical pathway in ovarian cancer cells. RNA interference-mediated silencing of NF-?B inducing kinase (NIK), a central regulator of the noncanonical pathway, reduced the NF-?B2/p52 DNA binding activity and NF-?B-dependent reporter gene expression as well as NF-?B target gene expression. Notably, anchorage-dependent and -independent cell growth was impaired in NIK-depleted cells. Depletion of NIK also suppressed tumor formation in the nude mouse xenograft assay. These results indicate that NIK plays a key role in constitutive NF-?B activation and the progression of ovarian cancer cells and suggest that NIK represents an attractive therapeutic target for ovarian cancer. PMID:24533079

Uno, Masaya; Saitoh, Yasunori; Mochida, Kanako; Tsuruyama, Eri; Kiyono, Tohru; Imoto, Issei; Inazawa, Johji; Yuasa, Yasuhito; Kubota, Toshiro; Yamaoka, Shoji

2014-01-01

369

Ultrasonic investigations near the B-induced quantum critical point of the triangular-lattice antiferromagnet Cs2CuCl4  

NASA Astrophysics Data System (ADS)

Measurements of the longitudinal elastic constants c11, c22 and c33 and the ultrasonic attenuation ? of the quasi-two-dimensional triangular-lattice spin-1/2 Heisenberg antiferromagnet Cs2CuCl4 reveal distinct anomalies near the B-induced quantum-critical point (QCP). These anomalies are particularly strongly pronounced in the ultrasonic attenuation. In isothermal field sweeps performed at low temperatures 0.027 K <= T <= 0.3 K around the saturation field Bs, the ultrasonic attenuation of all three modes shows a pronounced double-peak structure, indicating two anomalies of different origin. Upon cooling, however, both features merge suggesting a coincidence at the QCP. While one peak, which can be attributed to the ordering temperature TN(B), becomes critically enhanced upon approaching the QCP, the other one reduces in size and narrows upon cooling. The latter effect has been tentatively assigned to the material's spin-liquid features which precede the long-range antiferromagnetic ordering.

Wolf, B.; Cong, P. T.; Krüger, N.; Ritter, F.; Assmus, W.; Lang, M.

2012-12-01

370

Apigenin, a bioactive flavonoid from Lycopodium clavatum, stimulates nucleotide excision repair genes to protect skin keratinocytes from ultraviolet B-induced reactive oxygen species and DNA damage.  

PubMed

In this study, we examined the antioxidative and the DNA protective potentials of apigenin, a flavonoid polyphenol isolated from Lycopodium clavatum, in both in-vitro (HaCaT skin keratinocytes) and in-vivo (mice) models against UV-B radiation. We used DAPI staining in UV-B-irradiated HaCaT skin keratinocytes pre-treated with and without apigenin to assess DNA damage. We also used a flow-cytometric analysis in mice exposed to UV-B radiation with or without topical application of apigenin to assess, through a comet assay, chromosomal aberrations and quanta from reactive oxygen species (ROS) generation. Data from the stability curves for the Gibb's free energy determined from a melting-temperature profile study indicated that apigenin increased the stability of calf thymus DNA. Immunofluorescence studies revealed that apigenin caused a reduction in the number of cyclobutane pyrimidine dimers (CPDs) after 24 h, the time at which the nucleotide excision repair (NER) genes were activated. Thus, apigenin accelerated reversal of UV-B-induced CPDs through up-regulation of NER genes, removal of cyclobutane rings, inhibition of ROS generation, and down-regulation of NF-?B and MAPK, thereby revealing the precise mechanism of DNA repair. PMID:24139463

Das, Sreemanti; Das, Jayeeta; Paul, Avijit; Samadder, Asmita; Khuda-Bukhsh, Anisur Rahman

2013-10-01

371

NF-?B-Inducing Kinase in Thymic Stroma Establishes Central Tolerance by Orchestrating Cross-Talk with Not Only Thymocytes but Also Dendritic Cells.  

PubMed

Essential roles of NF-?B-inducing kinase (NIK) for the development of medullary thymic epithelial cells (mTECs) and regulatory T cells have been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice). However, the exact mechanisms underlying the defect in thymic cross-talk leading to the breakdown of self-tolerance in aly mice remain elusive. In this study, we demonstrated that production of regulatory T cells and the final maturation process of positively selected conventional ?? T cells are impaired in aly mice, partly because of a lack of mature mTECs. Of note, numbers of thymic dendritic cells and their expression of costimulatory molecules were also affected in aly mice in a thymic stroma-dependent manner. The results suggest a pivotal role of NIK in the thymic stroma in establishing self-tolerance by orchestrating cross-talk between mTECs and dendritic cells as well as thymocytes. In addition, we showed that negative selection was impaired in aly mice as a result of the stromal defect, which accounts for the development of organ-specific autoimmunity through a lack of normal NIK. PMID:25261487

Mouri, Yasuhiro; Nishijima, Hitoshi; Kawano, Hiroshi; Hirota, Fumiko; Sakaguchi, Nobuo; Morimoto, Junko; Matsumoto, Mitsuru

2014-11-01

372

Study of the Sorption and Separation Abilities of Commercial Solid?Phase Extraction (SPE) Cartridge Oasis MAX Towards Au(III), Pd(II), Pt(IV), and Rh(III)  

Microsoft Academic Search

This paper presents a new, simple, and rapid procedure for the separation and preconcentration of Au, Pt, Pd, and Rh based on the adsorption of the metals on a commercial solid?phase extraction (SPE) cartridge, Oasis MAX, which contains a polymeric resin with quaternary ammonium substituents. Adsorption studies revealed that the metal affinity towards the adsorbent ranked according to Au?Pd>Pt whereas

Manuela Hidalgo; Abdusalam Uheida; Victòria Salvadó; Clàudia Fontàs

2006-01-01

373

Determination of Non-Steroidal Anti-Inflammatory Drugs in Natural Waters Using Off-Line and On-Line SPE Followed by LC Coupled with DAD-MS  

Microsoft Academic Search

Two different procedures for simultaneous determination of six NSAIDs (diflunisal, diclofenac, fenoprofen, ibuprofen, naproxen\\u000a and tolmetin) in environmental waters are described. Final analysis of target compounds is performed by reversed-phase liquid\\u000a chromatography – diode array detection and mass spectrometry (HPLC-DAD and LC-MS), whereas sample preparation is based on\\u000a solid-phase extraction (SPE). A variety of sorbents and their respective advantages and

A. Kot-Wasik; J. D?bska; A. Wasik; J. Namie?nik

2006-01-01

374

Coupling HPLC-SPE-NMR with a microplate-based high-resolution antioxidant assay for efficient analysis of antioxidants in food--validation and proof-of-concept study with caper buds.  

PubMed

This work describes the coupling of a microplate-based antioxidant assay with a hyphenated system consisting of high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HPLC-SPE-NMR/high-resolution antioxidant assay, for the analysis of complex food extracts. The applicability of the microplate-based antioxidant assay for high-resolution screening of common food phenolics as well as parameters related to their trapping efficiency, elution behavior, and recovery on/from SPE cartridges are described. It was found that the microplate-based high-resolution antioxidant assay is an attractive and easy implementable alternative to direct on-line screening methods. Furthermore, it was shown that Resin SH and Resin GP SPE material are superior to RP C18HD for trapping of phenolic compounds. Proof-of-concept study was performed with caper bud extract, revealing the most important antioxidants to be quercetin, kaempferol, rutin, kaempferol-3-O-?-rutinoside and N(1),N(5),N(10)-triphenylpropenoyl spermidine amides. Targeted isolation of the latter, and comprehensive NMR experiments showed them to be N(1),N(10)-di-(E)-caffeoyl-N(5)-p-(E)-coumaroyl spermidine, N(1)-(E)-caffeoyl-N(5),N(10)-di-p-(E)-coumaroyl spermidine, N(10)-(E)-caffeoyl-N(1),N(5)-di-p-(E)-coumaroyl spermidine, and N(1),N(5),N(10)-tri-p-(E)-coumaroyl spermidine amides. PMID:23993578

Wiese, Stefanie; Wubshet, Sileshi G; Nielsen, John; Staerk, Dan

2013-12-15

375

The neuronal apoptosis inhibitory protein suppresses neuronal differentiation and apoptosis in PC12 cells.  

PubMed

The human neuronal apoptosis inhibitory protein (NAIP) gene has been discovered as a candidate gene for spinal muscular atrophy, a genetic disorder characterized by motor neuron loss in the spinal cord. The telomeric NAIP gene on human chromosome 5 is deleted together with survival motor neurons (SMN) in many cases of the most severe forms of the disorder. NAIP, c-IAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP, survivin and Apollon comprise the mammalian inhibitors of the apoptosis family and contain an N-terminal domain with 1-3 imperfect repeats of an approximately 65 amino acids domain named the baculovirus IAP repeat (BIR) motif. We identified six NAIP genes in the mouse genome which were found to be expressed in a broad range of tissues. Furthermore, we have investigated the effects of NAIP in the rat pheochromocytoma PC12 cell line. These cells differentiate in the presence of nerve growth factor (NGF) into cells that resemble sympathetic neurons. We observed that NAIP overexpression impaired NGF-induced neurite outgrowth. The BIR motifs of NAIP (residues 1-345) were not required for this effect. However, the BIR domains of NAIP were essential to prevent apoptosis in PC12 cells after NGF deprivation or TNF-alpha receptor stimulation. Expression of full-length but not BIR-deleted-NAIP protects against cell death. This correlates with reduced activity of the cell death effector protease, caspase-3, in lysates of NAIP-PC12 cells, as measured by cleavage of the fluorogenic tetrapeptide substrate Asp-Glu-Val-Asp. Thus, unregulation of cellular differentiation and/or caspase suppression may contribute to motoneuron dysfunction and cell death in spinal muscular atrophy where NAIP is mutated. PMID:11030753

Götz, R; Karch, C; Digby, M R; Troppmair, J; Rapp, U R; Sendtner, M

2000-10-12

376

Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization.  

PubMed

Granzyme B (GraB) induces apoptosis in the presence of perforin. Perforin polymerizes in the cell membrane to form a nonspecific ion pore, but it is not known where GraB acts to initiate the events that ultimately lead to apoptosis. It has been hypothesized that GraB enters the target cell through a perforin channel and then initiates apoptosis by cleaving and activating members of the ICE/Ced-3 family of cell death proteases. To determine if GraB can enter the cell, we treated YAC-1 or HeLa cells with FITC-labeled GraB and measured intracellular fluorescence with a high sensitivity CCD camera and image analyzer. GraB was internalized and found diffusely dispersed in the cell cytoplasm within 10 min. Uptake was inhibited at low temperature (4 degrees C) and by pretreatment with metabolic inhibitors, NaF and DNP, or cytochalasin B, a drug that both blocks microfilament formation, and FITC-GraB remained on the cell membrane localized in patches. With the simultaneous addition of perforin and FITC-GraB, no significant increase in cytoplasmic fluorescence was observed over that found in cells treated only with FITC-GraB. However, FITC-GraB was now detected in the nucleus of apoptotic cells labeling apoptotic bodies and localized areas within and along the nuclear membrane. The ability of GraB to enter cells in the absence of perforin was reexamined using anti-GraB antibody immunogold staining of ultrathin cryosections of cells incubated with GraB. Within 15 min, gold particles were detected both on the plasma membrane and in the cytoplasm of cells with some gold staining adjacent to the nuclear envelope but not in the nucleus. Cells internalizing GraB in the absence of perforin appeared morphologically normal by Hoechst staining and electron microscopy. GraB directly microinjected into the cytoplasm of B16 melanoma cells induced transient plasma membrane blebbing and nuclear coarsening but the cells did not become frankly apoptotic unless perforin was added. We conclude that GraB can enter cells autonomously but that perforin initiates the apoptotic process and the entry of GraB into the nucleus. PMID:9120391

Shi, L; Mai, S; Israels, S; Browne, K; Trapani, J A; Greenberg, A H

1997-03-01

377

The Tangled Circuitry of Metabolism and Apoptosis  

PubMed Central

For single cell organisms, nutrient uptake and metabolism are at the crux of their most basic decision of whether to grow or divide. In metazoans, cell fate decisions are more complex: organismal homeostasis must be strictly maintained by balancing cell proliferation and death. Despite this increased complexity, cell fate within multicellular organisms is also influenced by metabolism; recent studies, triggered in part be an interest tumor metabolism, are beginning to illuminate the mechanisms through which proliferation, death, and metabolism are intertwined. In particular, work on Bcl-2 family proteins suggests that the signaling pathways governing metabolism and apoptosis are inextricably linked. Here, we review the crosstalk between these pathways, emphasizing recent work that illustrates the emerging dual nature of several core apoptotic proteins in regulating both metabolism and cell death. PMID:23395270

Andersen, Joshua L.; Kornbluth, Sally

2013-01-01

378

[Role of HRI in apoptosis resistance].  

PubMed

When exposed to environmental stresses, cells activate defence mechanisms to adapt stress and inhibit apoptotic pathways leading to their survival. Stressed cells also reduce their general metabolism in part by inhibiting mRNA translation, thereby saving energy needed to repair stress-induced damages. Under stress conditions, the inhibition of mRNA translation occurs mainly at its initiation step through the phosphorylation of the translation initiation factor eIF2?. One of the four kinases known to phosphorylate eIF2? is heme-regulated inhibitor (HRI). The activation of HRI occurs under conditions of heme deficiency, oxidative stress and treatment with anti-cancer drugs such as proteasome inhibitors. In this article, we discuss the role of HRI in promoting cell resistance to stress-mediated apoptosis. PMID:25311023

Joncas, France-Hélène; Adjibade, Pauline; Mazroui, Rachid

2014-10-01

379

UV-B induced morphogenesis  

PubMed Central

Low levels of ultraviolet (UV)-radiation alter the morphology of plants. UV-B exposure can lead to shorter petioles and shorter, narrower and/or thicker leaf blades. The resulting decrease in leaf area has been associated with inhibitory UV-B effects on biomass accumulation. In Arabidopsis, UV-B effects on leaf area have variously been attributed to altered cell division, cell expansion or combinations of these two processes. A dedicated UV-B sensory system, crosstalk between flavonoids and auxins, endoreduplication and generic Stress Induced Morphogenic Responses (SIMR) have all been proposed to contribute to the UV-B phenotype. Here, we propose that UV-mediated morphogenesis, rather than being controlled by a single regulatory pathway, is controlled by a regulatory blur involving multiple compensatory molecular and physiological feedback interactions. PMID:22899069

Jansen, Marcel A.K.; Coffey, Aoife M.; Prinsen, Els

2012-01-01

380

Selective triggering of platelet apoptosis, platelet activation or both.  

PubMed

Anucleate platelets perform two fundamental processes, activation and apoptosis. We elaborated an approach for selective and concurrent stimulation of platelet apoptosis and/or activation, processes important in haemostasis and platelet clearance. Human platelets were treated with BH3 mimetic ABT-737, thrombin, calcium ionophore A23187 and matched diluents. Apoptosis was determined as mitochondrial inner membrane potential (??m) depolarization and activation as P-selectin exposure. At optimal treatment conditions (90-180 min, 37°C), ABT-737 predominantly induced apoptosis, when 77-81% platelets undergo only ??m depolarization. The ABT-737 impact on ??m depolarization is strongly time- and temperature-dependent, and much higher at 37°C than at room temperature. In contrast, when platelets were treated with thrombin for 15-90 min at either temperature, activation-only was predominantly (79-85%) induced, whereas A23187 triggers both apoptosis and activation (73-81%) when platelets were treated for 15-60 min at 37°C or 15-90 min at room temperature. These data demonstrate that, depending on the triggering stimulus, platelets predominantly undergo ??m depolarization-only, P-selectin exposure-only, or both responses, indicating that platelet apoptosis and activation are different phenomena driven by different mechanisms. The described model provides a basis for studying differential pharmacological manipulation of platelet apoptosis and activation and their role in haemostasis, thrombosis and platelet clearance. PMID:23398569

Gyulkhandanyan, Armen V; Mutlu, Asuman; Freedman, John; Leytin, Valery

2013-04-01

381

Role of Siglec-7 in Apoptosis in Human Platelets  

PubMed Central

Background Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis. Methodology/Principal Findings We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on ? granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (??m) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis. Conclusions/Significance The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention. PMID:25230315

Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Palle, Sabine; Anselme-Bertrand, Isabelle; Arthaud, Charles-Antoine; Chavarin, Patricia; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

2014-01-01

382

Fluorescent visualization of germline apoptosis in living Caenorhabditis elegans.  

PubMed

Visualization of apoptosis using fluorescent tools is quite straightforward in living Caenorhabditis elegans. Several transgenic lines are available that mark dying cells with fluorescent proteins, making it possible to quantify kinetics at various stages of the apoptotic process. Proteins required for the engulfment of cell corpses are particularly useful for detecting early apoptotic stages using this approach. For example, expression of the engulfment protein CED-1 fused to green fluorescent protein (CED-1::GFP) creates a halo around cells during early apoptosis, before their refractile morphology can be detected by differential interference contrast (DIC) optics. In addition, vital dyes such as acridine orange (AO) and SYTO-12 are selectively retained in apoptotic cells and can be used to visualize apoptosis in the germlines of living animals. It is also possible to use vital dyes in combination with transgenic strains expressing fluorescent markers of cell corpses to examine, in detail, multiple stages of apoptosis in vivo. Because of the high optical contrast of fluorescent reagents, apoptosis can be visualized even at low magnification, facilitating the use of screening platforms to identify apoptosis regulators. This protocol describes multiple uses of fluorescent reagents for visualization of germline apoptosis in living C. elegans, including AO staining, time-course studies using fluorescent proteins, and low-throughput screening of cell death genes using RNA interference (RNAi). PMID:24692492

Lant, Benjamin; Derry, W Brent

2014-04-01

383

Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis  

PubMed Central

Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD) nonalcoholic liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) viral hepatitis B and C (HBV, HCV). The critical step in the development of scar is activation of hepatic stellate cells (HSCs), which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression. PMID:22567408

Chakraborty, Jayashree Bagchi; Oakley, Fiona; Walsh, Meagan J.

2012-01-01

384

Apoptosis of human intestinal epithelial cells after bacterial invasion.  

PubMed Central

Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-macrophage cell lines, the commitment of human intestinal epithelial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h after bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program in the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic program. Apoptosis in response to bacterial infection may function to delete infected and damaged epithelial cells and restore epithelial cell growth regulation and epithelial integrity that are altered during the course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithelial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers. PMID:9819367

Kim, J M; Eckmann, L; Savidge, T C; Lowe, D C; Witthoft, T; Kagnoff, M F

1998-01-01

385

Lysine methyltransferase Smyd2 suppresses p53-dependent cardiomyocyte apoptosis.  

PubMed

Apoptosis, or programmed cell death, is an essential physiological process for proper embryogenesis as well as for homeostasis during aging. In addition, apoptosis is one of the major mechanisms causing cell loss in pathophysiological conditions such as heart failure. Thus, inhibition of apoptosis is an important approach for preventive and therapeutic strategies. Here we show that the histone 3 lysine 4- and lysine 36-specific methyltransferase Smyd2 acts as an endogenous antagonistic player of p53-dependent cardiomyocyte apoptosis. Smyd2 protein levels were significantly decreased in cardiomyocytes upon cobalt chloride-induced apoptosis or myocardial infarction, while p53 expression was enhanced. siRNA-mediated knockdown of Smyd2 in cultured cardiomyocytes further enhanced cobalt chloride-induced cardiomyocyte apoptosis. In contrast, Smyd2 overexpression resulted in marked methylation of p53 and prevented its accumulation as well as apoptotic cell death in an Hsp90-independent manner. Moreover, overexpression, of Smyd2, but not Smyd2Y240F lacking a methyl transferase activity, significantly rescued CoCl2-induced apoptosis in H9c2 cardioblasts. Finally, Smyd2 cardiomyocyte-specific deletion in vivo promoted apoptotic cell death upon myocardial infarction, which correlated with enhanced expression of p53 and pro-apoptotic Bax. Collectively, our data indicate Smyd2 as a cardioprotective protein by methylating p53. PMID:25014164

Sajjad, Amna; Novoyatleva, Tatyana; Vergarajauregui, Silvia; Troidl, Christian; Schermuly, Ralph T; Tucker, Haley O; Engel, Felix B

2014-11-01

386

Smad2 is Involved in Aggregatibacter actinomycetemcomitans-induced Apoptosis.  

PubMed

Apoptosis is thought to contribute to the progression of periodontitis. It has been suggested that the apoptosis of epithelial cells may contribute to the loss of epithelial barrier function. Smad2, a downstream signaling molecule of TGF-? receptors (TGF-?Rs), is critically involved in apoptosis in several cell types. However, the relationship between smad2 and bacteria-induced apoptosis has not yet been elucidated. It is possible that the regulation of apoptosis induced by periodontopathic bacteria may lead to novel preventive therapies for periodontitis. Therefore, in the present study, we investigated the involvement of smad2 phosphorylation in apoptosis of human gingival epithelial cells induced by Aggregatibacter actinomycetemcomitans (Aa). Aa apparently induced the phosphorylation of smad2 in primary human gingival epithelial cells (HGECs) or the human gingival epithelial cell line, OBA9 cells. In addition, Aa induced phosphorylation of the serine residue of the TGF-? type I receptor (TGF-?RI) in OBA9 cells. SB431542 (a TGF-?RI inhibitor) and siRNA transfection for TGF-?RI, which reduced both TGF-?RI mRNA and protein levels, markedly attenuated the Aa-induced phosphorylation of smad2. Furthermore, the disruption of TGF-?RI signaling cascade by SB431542 and siRNA transfection for TGF-?RI abrogated the activation of cleaved caspase-3 expression and repressed apoptosis in OBA9 cells treated with Aa. Thus, Aa induced apoptosis in gingival epithelial cells by activating the TGF-?RI-smad2-caspase-3 signaling pathway. The results of the present study may suggest that the periodontopathic bacteria, Aa, activates the TGF-?R/smad2 signaling pathway in human gingival epithelial cells and induces apoptosis in epithelial cells, which may lead to new therapeutic strategies that modulate the initiation of periodontitis. PMID:25192897

Yoshimoto, T; Fujita, T; Ouhara, K; Kajiya, M; Imai, H; Shiba, H; Kurihara, H

2014-11-01

387

Apoptosis of circulating lymphocytes during pediatric cardiac surgery  

NASA Astrophysics Data System (ADS)

There is a constant need for clinical diagnostic systems that enable to predict disease course for preventative medicine. Apoptosis, programmed cell death, is the end point of the cell's response to different induction and leads to changes in the cell morphology that can be rapidly detected by optical systems. We tested whether apoptosis of T-cells in the peripheral blood is useful as predictor and compared different preparation and analytical techniques. Surgical trauma is associated with elevated apoptosis of circulating leukocytes. Increased apoptosis leads to partial removal of immune competent cells and could therefore in part be responsible for reduced immune defence. Cardiovascular surgery with but not without cardiopulmonary bypass (CPB) induces transient immunosuppression. Its effect on T-cell apoptosis has not been shown yet. Flow-cytometric data of blood samples from 107 children (age 3-16 yr.) who underwent cardiac surgery with (78) or without (29) CPB were analysed. Apoptotic T-lymphocytes were detected based on light scatter and surface antigen (CD45/CD3) expression (ClinExpImmunol2000;120:454). Results were compared to staining with CD3 antibodies alone and in the absence of antibodies. T-cell apoptosis rate was comparable when detected with CD45/CD3 or CD3 alone, however not in the absence of CD3. Patients with but not without CPB surgery had elevated lymphocyte apoptosis. T-cell apoptosis increased from 0.47% (baseline) to 0.97% (1 day postoperatively). In CPB patients with complication 1.10% significantly higher (ANOVA p=0.01) comparing to CPB patients without complications. Quantitation of circulating apoptotic cells based on light scatter seems an interesting new parameter for diagnosis. Increased apoptosis of circulating lymphocytes and neutrophils further contributes to the immune suppressive response to surgery with CPB. (Support: MP, Deutsche Herzstiftung, Frankfurt, Germany)

Bocsi, J.; Pipek, M.; Hambsch, J.; Schneider, P.; Tárnok, A.

2006-02-01

388

Evaluation of ?-Induced Apoptosis in Human Peripheral Blood Lymphocytes  

NASA Astrophysics Data System (ADS)

Several experiments have been performed to study regularities in the induction of apoptotic cells in human lymphocytes by 60Co ?-rays at different times after irradiation. Apoptosis induction by 60Co ?-rays in human lymphocytes in different cell cycle phases (G0, S, G1, and G2) has been studied. The maximal apoptosis output in lymphocyte cells was observed in the S phase. Modifying effect of replicative and reparative DNA synthesis inhibitors—1- ? -D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (Hu)—on the kinetics of 60Co ?-rays induced apoptosis in human lymphocytes has been studied.

Baranova, Elena; Boreyko, Alla; Ravnachka, Ivanka; Saveleva, Maria

2010-01-01

389

Radiation-induced apoptosis in the eye structures: a review  

NASA Astrophysics Data System (ADS)

Apoptosis plays a crucial role in tissue homeostasis and in the removal of damaged cells from tissues. Both increased and insufficient cell death can lead to human diseases. Apoptotic process is under the control of physiological metabolism as well as a panel of genes. After exposure to radiation, membrane damages induce the membrane pathway signal transduction for cell apoptosis. The importance of the radiation-induced apoptosis in the different ocular tissues and its relationship to the radiation parameters are reviewed in this article. This topic of ocular research has not been addressed in detail in the literature.

Belkacémi, Yazid; Huchet, Aymeri; Baudouin, Christophe; Lartigau, Éric

2005-02-01

390

SPE-HPLC method for the determination of four flavonols in rat plasma and urine after oral administration of Abelmoschus manihot extract.  

PubMed

A SPE-HPLC method was developed and validated for the simultaneous determination of flavonols, isoquercitrin (1), hibifolin (2), myricetin (3), quercetin-3'-O-d-glucoside (4) and quercetin (5) in rat plasma and urine after oral administration of the total flavonoids from Abelmoschus manihot (TFA). The astragalin (6) and kaempferol (7) were used as internal standards (IS). Plasma and urine samples were pretreated by solid-phase extraction using Winchem C(18) reversed-phase cartridges. Analysis of the plasma and urinary extract was performed on YMC-Pack ODS-A C(18) and Thermo ODS-2HYEPRSIL C(18) reversed-phase column, respectively and a mobile phase of acetonitrile-0.1% phosphoric acid was employed. HPLC analysis was conducted with different elution gradients. The flow rate was 1.0 mL/min and the detection wavelength was set at 370 nm. Calibration ranges in plasma for flavonols 2-5 were at 0.011-2.220, 0.014-2.856, 0.022-4.320, and 0.028-5.600 microg/mL, respectively. In urine calibration ranges for flavonols 1, 2, 4 and 5 were at 2.00-16.00, 8.56-102.72, 2.70-21.60, and 3.00-24.00 microg/mL, respectively. The RSD of intra- and inter-day was less than 5.40% and 4.89% in plasma, and less than 3.96% and 6.85% in urine for all the analyses. A preliminary experiment to investigate the plasma concentration and urinary excretion of the flavonols after oral administration of TFA to rats demonstrated that the present method was suitable for determining the flavonols in rat plasma and urine. PMID:17258944

Lai, Xianyin; Zhao, Yuying; Liang, Hong; Bai, Yanjing; Wang, Bin; Guo, Dean

2007-06-01

391

1H NMR-based metabolomics combined with HPLC-PDA-MS-SPE-NMR for investigation of standardized Ginkgo biloba preparations  

PubMed Central

Commercial preparations of Ginkgo biloba are very complex mixtures prepared from raw leaf extracts by a series of extraction and prepurification steps. The pharmacological activity is attributed to a number of flavonoid glycosides and unique terpene trilactones (TTLs), with largely uncharacterized pharmacological profiles on targets involved in neurological disorders. It is therefore important to complement existing targeted analytical methods for analysis of Ginkgo biloba preparations with alternative technology platforms for their comprehensive and global characterization. In this work, 1H NMR-based metabolomics and hyphenation of high-performance liquid chromatography, photo-diode array detection, mass spectrometry, solid-phase extraction, and nuclear magnetic resonance spectroscopy (HPLC-PDA-MS-SPE-NMR) were used for investigation of 16 commercially available preparations of Ginkgo biloba. The standardized extracts originated from Denmark, Italy, Sweden, and United Kingdom, and the results show that 1H NMR spectra allow simultaneous assessment of the content as well as identity of flavonoid glycosides and TTLs based on a very simple sample-preparation procedure consisting of extraction, evaporation and reconstitution in acetone-d6. Unexpected or unwanted extract constituents were also easily identified in the 1H NMR spectra, which contrasts traditional methods that depend on UV absorption or MS ionizability and usually require availability of reference standards. Automated integration of 1H NMR spectral segments (buckets or bins of 0.02 ppm width) provides relative distribution plots of TTLs based on their H-12 resonances. The present study shows that 1H NMR-based metabolomics is an attractive method for non-selective and comprehensive analysis of Ginkgo extracts. Electronic supplementary material The online version of this article (doi:10.1007/s11306-009-0195-x) contains supplementary material, which is available to authorized users. PMID:20526353

Agnolet, Sara; Jaroszewski, Jerzy W.; Verpoorte, Robert

2010-01-01

392

WINGS-SPE II: A catalog of stellar ages and star formation histories, stellar masses and dust extinction values for local clusters galaxies  

NASA Astrophysics Data System (ADS)

Context. The WIde-field Nearby Galaxy clusters Survey (wings) is a project whose primary goal is to study the galaxy populations in clusters in the local universe (z < 0.07) and of the influence of environment on their stellar populations. This survey has provided the astronomical community with a high quality set of photometric and spectroscopic data for 77 and 48 nearby galaxy clusters, respectively. Aims: In this paper we present the catalog containing the properties of galaxies observed by the wings SPEctroscopic (wings-spe) survey, which were derived using stellar populations synthesis modelling approach. We also check the consistency of our results with other data in the literature. Methods: Using a spectrophotometric model that reproduces the main features of observed spectra by summing the theoretical spectra of simple stellar populations of different ages, we derive the stellar masses, star formation histories, average age and dust attenuation of galaxies in our sample. Results: ~ 5300 spectra were analyzed with spectrophotometric techniques, and this allowed us to derive the star formation history, stellar masses and ages, and extinction for the wings spectroscopic sample that we present in this paper. Conclusions: The comparison with the total mass values of the same galaxies derived by other authors based on sdss data, confirms the reliability of the adopted methods and data. Based on observations taken at the Anglo Australian Telescope (3.9 m- AAT), and at the William Herschel Telescope (4.2 m- WHT).Full Table 2 is available in electronic form both at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/526/A45, and by querying the wings database at http://web.oapd.inaf.it/wings/new/index.html

Fritz, J.; Poggianti, B. M.; Cava, A.; Valentinuzzi, T.; Moretti, A.; Bettoni, D.; Bressan, A.; Couch, W. J.; D'Onofrio, M.; Dressler, A.; Fasano, G.; Kjærgaard, P.; Moles, M.; Omizzolo, A.; Varela, J.

2011-02-01

393

“Killing the Blues”: A role for cellular suicide (apoptosis) in depression and the antidepressant response?  

Microsoft Academic Search

Apoptosis or programmed cell death is a critical regulator of tissue homeostasis and emerging evidence is focused on the role of apoptosis mechanisms in the central nervous system. Generally, apoptosis is necessary to prevent cancerous growths. However, excessive apoptosis in post-mitotic cells such as neurons leads to neurodegeneration. Chronic stress, which can precipitate depression, has been shown to increase the

Declan P. McKernan; Timothy G. Dinan; John F. Cryan

2009-01-01

394

Caspase Pro-Domains and the Regulation of Apoptosis.  

National Technical Information Service (NTIS)

Apoptosis is a program of cellular suicide which results in the removal of damaged or superfluous cells without causing overall changes in tissue architecture. Apoptotic cellular destruction is carried out by a family of proteases known as the caspases. U...

S. Kornbluth

2000-01-01

395

Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis.  

PubMed

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a promising antitumor therapy. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL, highlighting the need for strategies to overcome TRAIL resistance. Here we show that in combination with phenethyl isothiocyanate (PEITC), exposure to TRAIL induced apoptosis in TRAIL-resistant glioma cells. Subtoxic concentrations of PEITC significantly potentiated TRAIL-induced cytotoxicity and apoptosis in glioma cells. PEITC dramatically upregulated DR5 receptor expression but had no effects on DR4 receptor. PEITC enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-induced-p53. PMID:24491546

Lee, Dae-Hee; Kim, Dong-Wook; Lee, Hai-Chon; Lee, Jung-Hyun; Lee, Tae-Hwa

2014-04-18

396

Norcantharidin Induces HL-60 Cells Apoptosis In Vitro.  

PubMed

Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris, and is known to have anticancer potentials. The aim of this paper was to assess the apoptosis-inducing effect of NCTD on HL-60 cells. Methods. The effects of NCTD were detected by flow cytometer on the cell toxicity, cell cycle, and apoptosis of HL-60 cells cultured in vitro. Results. After 48-hour treatment with NCTD, the growth of HL-60 cells was inhibited significantly. The summit of apoptosis appeared after 24 hours. The percentage of the cells in G(1) phase decreased and then increased in S and G(2)+ M phase, while the S and G(2)+ M phases were blocked after treatment with 5, 10, and 50??mol/L NCTD for 24 hours. Conclusions. NCTD can induce the apoptosis of HL-60 cells and inhibit the fissiparism, and the domino effect was obviously correlated with the time and dosage. PMID:22778770

Jiang, You-Ming; Meng, Zhen-Zhi; Yue, Guang-Xin; Chen, Jia-Xu

2012-01-01

397

Norcantharidin Induces HL-60 Cells Apoptosis In Vitro  

PubMed Central

Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris, and is known to have anticancer potentials. The aim of this paper was to assess the apoptosis-inducing effect of NCTD on HL-60 cells. Methods. The effects of NCTD were detected by flow cytometer on the cell toxicity, cell cycle, and apoptosis of HL-60 cells cultured in vitro. Results. After 48-hour treatment with NCTD, the growth of HL-60 cells was inhibited significantly. The summit of apoptosis appeared after 24 hours. The percentage of the cells in G1 phase decreased and then increased in S and G2+ M phase, while the S and G2+ M phases were blocked after treatment with 5, 10, and 50??mol/L NCTD for 24 hours. Conclusions. NCTD can induce the apoptosis of HL-60 cells and inhibit the fissiparism, and the domino effect was obviously correlated with the time and dosage. PMID:22778770

Jiang, You-Ming; Meng, Zhen-Zhi; Yue, Guang-Xin; Chen, Jia-Xu

2012-01-01

398

Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis.  

National Technical Information Service (NTIS)

Ebolavirus (EBOV) is a member of the filovirus family and causes severe hemorrhagic fever, resulting in death in up to 90% of infected humans. EBOV infection induces massive bystander lymphocyte apoptosis; however, neither the cellular apoptotic pathway(s...

E. Watanabe, J. E. McDunn, M. A. Smith, P. E. Swanson, S. B. Bradfute

2010-01-01

399

Brazilin inhibits growth and induces apoptosis in human glioblastoma cells.  

PubMed

Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7. PMID:23429418

Lee, Dae-Young; Lee, Mi-Kyoung; Kim, Geum-Soog; Noh, Hyung-Jun; Lee, Min-Ho

2013-01-01

400

Apoptosis and the target genes of microRNA-21  

PubMed Central

MicroRNA-21 (miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors. Through functional suppression, miR-21 is implicated in practically every walk of oncogenic life: the promotion of cell proliferation, invasion and metastasis, genome instability and mutation, inflammation, replicative immortalization, abnormal metabolism, angiogenesis, and evading apoptosis, immune destruction, and growth suppressors. In particular, miR-21 is strongly involved in apoptosis. In this article, we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis. This suggests that miR-21 is an Oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21. PMID:21627859

Buscaglia, Lindsey E. Becker; Li, Yong

2011-01-01

401

CONFOCAL LASER SCANNING MICROSCOPY OF APOPTOSIS IN WHOLE MOUSE OVARIES  

EPA Science Inventory

Confocal Laser Scanning Microscopy of Apoptosis in Whole Mouse Ovaries. Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle...

402

Visualizing Vpr-induced G2 arrest and apoptosis.  

PubMed

Vpr is an accessory protein of human immunodeficiency virus type 1 (HIV-1) with multiple functions. The induction of G2 arrest by Vpr plays a particularly important role in efficient viral replication because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. The regulation of apoptosis by Vpr is also important for immune suppression and pathogenesis during HIV infection. However, it is not known whether Vpr-induced apoptosis depends on the ability of Vpr to induce G2 arrest, and the dynamics of Vpr-induced G2 arrest and apoptosis have not been visualized. We performed time-lapse imaging to examine the temporal relationship between Vpr-induced G2 arrest and apoptosis using HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator2 (Fucci2). The dynamics of G2 arrest and subsequent long-term mitotic cell rounding in cells transfected with the Vpr-expression vector were visualized. These cells underwent nuclear mis-segregation after prolonged mitotic processes and then entered G1 phase. Some cells subsequently displayed evidence of apoptosis after prolonged mitotic processes and nuclear mis-segregation. Interestingly, Vpr-induced apoptosis was seldom observed in S or G2 phase. Likewise, visualization of synchronized HeLa/Fucci2 cells infected with an adenoviral vector expressing Vpr clearly showed that Vpr arrests the cell cycle at G2 phase, but does not induce apoptosis at S or G2 phase. Furthermore, time-lapse imaging of HeLa/Fucci2 cells expressing SCAT3.1, a caspase-3-sensitive fusion protein, clearly demonstrated that Vpr induces caspase-3-dependent apoptosis. Finally, to examine whether the effects of Vpr on G2 arrest and apoptosis were reversible, we performed live-cell imaging of a destabilizing domain fusion Vpr, which enabled rapid stabilization and destabilization by Shield1. The effects of Vpr on G2 arrest and subsequent apoptosis were reversible. This study is the first to characterize the dynamics of the morphological changes that occur during Vpr-induced G2 arrest and apoptosis. PMID:24466265

Murakami, Tomoyuki; Aida, Yoko

2014-01-01

403

Induction of Oligodendrocyte Apoptosis by C 2 Ceramide  

Microsoft Academic Search

Tumor necrosis factor-a induces oligodendrocytes apoptosis, and is known to stimulate the hydrolysis of sphingomyelin to form the lipid mediator, ceramide. These data encouraged us to determine whether ceramide itself is able to induce apoptosis in oligodendrocytes. For this purpose the cell-permeable ceramide analog, C2-ceramide was used. Treatment of bovine oligodendrocyte cell cultures with this compound induced cell death in

J. N. Larocca; M. Farooq; W. T. Norton

1997-01-01

404

Induction of apoptosis in human HaCaT keratinocytes  

Microsoft Academic Search

Although cell death by apoptosis has been recognized as an important control mechanism in the maintenance of tissue homeostasis\\u000a and in the elimination of cells with damaged DNA, information on the induction and characteristics of apoptosis in keratinocytes\\u000a is rather scarce. Apoptotic mechanisms may play an important role in normal and disturbed homeostasis of the skin. In the\\u000a present study,

Ute Henseleit; Thomas Rosenbach; Gerhard Kolde

1996-01-01

405

Abnormalities of cell structures in tumors: apoptosis in tumors  

Microsoft Academic Search

A conceptual shift has occurred in recent years from considering cancer as simply a disease of deregulated cell proliferation\\u000a to a view that incorporates the aberrant control of apoptosis into the equation. Apoptosis is an organized, genetically programmed\\u000a cell death process by which multicellular organisms specifically destroy, dismantle and dispose of cells. In cancer cells,\\u000a this tightly controlled process is

Herman H. Cheung; Vinay Arora; Robert G. Korneluk

406

Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection  

PubMed Central

HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal antivirals that eliminate viral infection by destroying infected cells. A drug-based drug discovery program, based on these compounds, is warranted to determine the potential of such agents in clinical trials of HIV-infected patients. PMID:24086341

Hanauske-Abel, Hartmut M.; Saxena, Deepti; Palumbo, Paul E.; Hanauske, Axel-Rainer; Luchessi, Augusto D.; Cambiaghi, Tavane D.; Hoque, Mainul; Spino, Michael; Gandolfi, Darlene D'Alliessi; Heller, Debra S.; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M.; Tricta, Fernando; Connelly, John; Popowicz, Anthony M.; Cone, Richard A.; Holland, Bart; Pe'ery, Tsafi; Mathews, Michael B.

2013-01-01

407

A Plant Defense Response Effector Induces Microbial Apoptosis  

Microsoft Academic Search

Osmotin is a tobacco PR-5 protein that has antifungal activity and is implicated in host-plant defense. We show here that osmotin induces apoptosis in Saccharomyces cerevisiae. Induction of apoptosis was correlated with intracellular accumulation of reactive oxygen species and was mediated by RAS2, but not RAS1. Osmotin treatment resulted in suppression of transcription of stress-responsive genes via the RAS2\\/cAMP pathway.

Meena L Narasimhan; Barbara Damsz; Maria A Coca; José I Ibeas; Dae-Jin Yun; José M Pardo; Paul M Hasegawa; Ray A Bressan

2001-01-01

408

Induction of apoptosis in fibroblasts by c-myc protein  

Microsoft Academic Search

Summary Although Rat-l fibroblasts expressing c-myc constitu- tively are unable to arrest growth in low serum, their numbers do not increase in culture because of sub- stantial cell death. We show this cell death to be depen- dent upon expression of c-myc protein and to occur by apoptosis. Regions of the c-myc protein required for induction of apoptosis overlap with

Gerard I. Evan; Andrew H. Wyllie; Christopher S. Gilbert; Trevor D. Littlewood; Mary Brooks; Catherine M. Waters; David C. Hancock

1992-01-01

409

Apoptosis, oncosis, and necrosis. An overview of cell death.  

PubMed Central

The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7856735

Majno, G.; Joris, I.

1995-01-01

410

Does atorvastatin induce aortic smooth muscle cell apoptosis in vivo?  

PubMed

It has been reported that HMG-CoA reductase inhibitors such as atorvastatin induce vascular smooth muscle cell (SMC) apoptosis in vitro. However, this effect remains to be demonstrated in vivo. The present studies were designed to test the ability of atorvastatin to induce SMC apoptosis in vivo, using the spontaneously hypertensive rat (SHR) as a well-known reference model of SMC apoptosis induction in vivo by cardiovascular drugs including the calcium channel blocker amlodipine. Atorvastatin was administered to SHR for 3 or 6 weeks either alone or together with amlodipine, a drug combination clinically available to patients. Primary endpoints included aortic medial hypertrophy and aortic SMC hyperplasia, internucleosomal DNA fragmentation and expression of the apoptosis regulatory proteins Bax and Bcl-2. The SHR aorta showed no evidence of SMC apoptosis induction by atorvastatin, even at the high dose of 50 mg kg(-1) day(-1), although the statin significantly reduced oxidative stress after 3 weeks and blood pressure after 6 weeks of administration. Amlodipine-induced regression of aortic hypertophy and aortic SMC hyperplasia were dose- and time-dependent, but there was no interaction between atorvastatin and amlodipine in modulating the primary endpoints. These results do not support the notion that atorvastatin induces SMC apoptosis in the aortic media in vivo. PMID:20951229

Doyon, Marielle; Hale, Taben Mary; Huot-Marchand, Julie-Emilie; Wu, Rong; de Champlain, Jacques; DeBlois, Denis

2011-01-01

411

The retinoblastoma protein induces apoptosis directly at the mitochondria  

PubMed Central

The retinoblastoma protein gene RB-1 is mutated in one-third of human tumors. Its protein product, pRB (retinoblastoma protein), functions as a transcriptional coregulator in many fundamental cellular processes. Here, we report a nonnuclear role for pRB in apoptosis induction via pRB's direct participation in mitochondrial apoptosis. We uncovered this activity by finding that pRB potentiated TNF?-induced apoptosis even when translation was blocked. This proapoptotic function was highly BAX-dependent, suggesting a role in mitochondrial apoptosis, and accordingly, a fraction of endogenous pRB constitutively associated with mitochondria. Remarkably, we found that recombinant pRB was sufficient to trigger the BAX-dependent permeabilization of mitochondria or liposomes in vitro. Moreover, pRB interacted with BAX in vivo and could directly bind and conformationally activate BAX in vitro. Finally, by targeting pRB specifically to mitochondria, we generated a mutant that lacked pRB's classic nuclear roles. This mito-tagged pRB retained the ability to promote apoptosis in response to TNF? and also additional apoptotic stimuli. Most importantly, induced expression of mito-tagged pRB in Rb?/?;p53?/? tumors was sufficient to block further tumor development. Together, these data establish a nontranscriptional role for pRB in direct activation of BAX and mitochondrial apoptosis in response to diverse stimuli, which is profoundly tumor-suppressive. PMID:23618872

Hilgendorf, Keren I.; Leshchiner, Elizaveta S.; Nedelcu, Simona; Maynard, Mindy A.; Calo, Eliezer; Ianari, Alessandra; Walensky, Loren D.; Lees, Jacqueline A.

2013-01-01

412

Research advances on apoptosis caused by quantum dots.  

PubMed

Recently, quantum dots (QDs) have been widely applied in biological and biomedical fields such as cell labeling, living tissue imaging, and photodynamic therapy because of their superior optical properties. Meanwhile, the potential biological negative effects and/or toxic effects of QDs have become increasingly important, especially the cytotoxicity caused by QDs. One of the common cytotoxicity when living organisms are treated with QD is apoptosis, where many attempts have been made to explain the mechanisms of apoptosis caused by QDs' use. One of the mechanisms is the production of cadmium ion (Cd(2+)) and reactive oxygen species (ROS). Excess generation of ROS will result in oxidative stress that would mediate apoptosis. Furthermore, the activation of cell death receptors and mitochondria-dependent such as B cell lymphoma 2 (Bcl-2) family and the caspase family could onset apoptosis. Signal transduction such as some classical signal pathways of PI3K-AKT, NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa B (NF-?B) also plays an important role in the regulation of apoptosis. Several ways to reduce the apoptotic rate have been introduced, such as surface modification, controlling, the dose, size, and exposure time of QDs as well as using antioxidants or inhibitors. In this review, we attempted to review the most recent findings associated with apoptosis caused by QDs so as to provide some guidelines for a safer QD application in the future. PMID:25062887

Zhan, Qingling; Tang, Meng

2014-10-01

413

Hydrogen peroxide induces apoptosis via a mitochondrial pathway in chondrocytes  

NASA Astrophysics Data System (ADS)

The degenerative joint disease such as osteoarthritis (OA) is closely associated with the death of chondrocytes in apoptosis fashion. Hydrogen peroxide (H2O2), higher expression following acute damage in OA patients, has been shown to be up-regulated during apoptosis in a bulk of experimental models. This study was aimed to explore the mechanism of H2O2-induced rabbit chondrocytes apoptosis. Articular cartilage was biopsied from the joints of 6 weeks old New Zealand rabbits. Cell Counting Kit (CCK-8) assay was used to assess the inhibitory effect of H2O2 on cell viability. H2O2 treatment induced a remarkable reduction of cell viability. We used flow cytometry to assess the form of cell death with Annexin-V/PI double staining, and found that H2O2 treatment induced apoptosis in a dose-and time-dependent manner. Exposure of chondrocytes to 1.5 mM of H2O2 for 2 h induced a burst apoptosis that can be alleviated by N-acetyl cysteine (NAC) pretreatment, an anti-oxidant amino-acid derivative. Loss of mitochondria membrane potential (??m) was evaluated using confocal microscopy imaging and flow cytometry (FCM). H2O2 treatment induced a marked reduction of ??m, and the abrupt disappearance of ??m occurred within 5 minutes. These results indicate that H2O2 induces a rapid apoptosis via a mitochondrial pathway in rabbit chondrocytes.

Zhuang, Cai-ping; Liang, Qian; Wang, Xiao-ping; Chen, Tong-sheng

2012-03-01

414

A Translocated Bacterial Protein Protects Vascular Endothelial Cells from Apoptosis  

PubMed Central

The modulation of host cell apoptosis by bacterial pathogens is of critical importance for the outcome of the infection process. The capacity of Bartonella henselae and B. quintana to cause vascular tumor formation in immunocompromised patients is linked to the inhibition of vascular endothelial cell (EC) apoptosis. Here, we show that translocation of BepA, a type IV secretion (T4S) substrate, is necessary and sufficient to inhibit EC apoptosis. Ectopic expression in ECs allowed mapping of the anti-apoptotic activity of BepA to the Bep intracellular delivery domain, which, as part of the signal for T4S, is conserved in other T4S substrates. The anti-apoptotic activity appeared to be limited to BepA orthologs of B. henselae and B. quintana and correlated with (i) protein localization to the host cell plasma membrane, (ii) elevated levels of intracellular cyclic adenosine monophosphate (cAMP), and (iii) increased expression of cAMP-responsive genes. The pharmacological elevation of cAMP levels protected ECs from apoptosis, indicating that BepA mediates anti-apoptosis by heightening cAMP levels by a plasma membrane–associated mechanism. Finally, we demonstrate that BepA mediates protection of ECs against apoptosis triggered by cytotoxic T lymphocytes, suggesting a physiological context in which the anti-apoptotic activity of BepA contributes to tumor formation in the chronically infected vascular endothelium. PMID:17121462

Schmid, Michael C; Scheidegger, Florine; Dehio, Michaela; Balmelle-Devaux, Nadege; Schulein, Ralf; Guye, Patrick; Chennakesava, Cuddapah S; Biedermann, Barbara; Dehio, Christoph

2006-01-01

415

Overexpression of ornithine decarboxylase suppresses thapsigargin-induced apoptosis.  

PubMed

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca(2+) ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspase-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and down-stream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway. PMID:20814750

Hsieh, Wei-Chung; Hsu, Pei-Chen; Liao, Ya-Fan; Young, Shu-Ting; Wang, Zeng-Wei; Lin, Chih-Li; Tsay, Gregory J; Lee, Huei; Hung, Hui-Chih; Liu, Guang-Yaw

2010-10-01

416

Apoptosis induced by adenosine in human leukemia HL-60 cells.  

PubMed

Among several nucleosides and nucleotides, which showed strong inhibition of growth of HL-60 cells, only adenosine (Ado) specifically induced typical apoptotic death of the cells, accompanying double-strand cleavage of DNA into nucleosomal size fragments, and subsequent apoptotic body formation. A marked enhancement of endogenous poly(ADP-ribosyl)ation activity in the cell was detected at a relatively early stage of cell death, whereas other nucleosides and nucleotides tested were ineffective on poly(ADP-ribosyl)ation activity, suggesting that the enzyme activation is closely related to apoptosis. The observed Ado effect was not mediated by Ado receptors, in contrast to the Ado-induced apoptotic death of thymocytes, judging from the facts that all of the receptor agonists tested did not substitute for Ado and that a receptor antagonist did not inhibit the effect of Ado. Ado transport into the cell seemed to be essential for the induction of apoptosis, since an inhibitor of Ado transport (dipyridamole) strongly suppressed apoptosis. Cytochalasin B blocked Ado-induced apoptotic body formation without affecting activation of endogenous poly(ADP-ribosyl)ation activity in the cell. Thus, the process of apoptosis in HL-60 cells induced by Ado seems to be separated into at least two steps, an initial step of DNA degradation and a following morphological change. While the adenine moiety of Ado was essential for its apoptosis-inducing activity, the sugar was replaceable, and various analogs with modified sugar were inducers of apoptosis, although they were less efficient than Ado. PMID:8020596

Tanaka, Y; Yoshihara, K; Tsuyuki, M; Kamiya, T

1994-07-01

417

Noxa couples lysosomal membrane permeabilization and apoptosis during oxidative stress.  

PubMed

The exact roles of lysosomal membrane permeabilization (LMP) in oxidative stress-triggered apoptosis are not completely understood. Here, we first studied the temporal relation between LMP and mitochondrial outer membrane permeabilization (MOMP) during the initial stage of apoptosis caused by the oxidative stress inducer H2O2. Despite its essential role in mediating apoptosis, the expression of the BH3-only Bcl-2 protein Noxa was dispensable for LMP. In contrast, MOMP was dependent on Noxa expression and occurred downstream of LMP. When lysosomal membranes were stabilized by the iron-chelating agent desferrioxamine, H2O2-induced increase in DNA damage, Noxa expression, and subsequent apoptosis were abolished by the inhibition of LMP. Importantly, LMP-induced Noxa expression increase was mediated by p53 and seems to be a unique feature of apoptosis caused by oxidative stress. Finally, exogenous iron loading recapitulated the effects of H2O2 on the expression of BH3-only Bcl-2 proteins. Overall, these data reveal a Noxa-mediated signaling pathway that couples LMP with MOMP and ultimate apoptosis during oxidative stress. PMID:23770082

Eno, Colins O; Zhao, Guoping; Venkatanarayan, Avinashnarayan; Wang, Bing; Flores, Elsa R; Li, Chi

2013-12-01

418

FAQ IRB questions (includes SPE  

Cancer.gov

The most recent Investigator’s Brochure (IB) will provide a good estimate of known adverse event inci-dence (see the FAQ on how to receive an IB), and some CAEPRs (included in the protocol docu-ment) do, too.

419

Cord Blood Stem Cell-Mediated Induction of Apoptosis in Glioma Downregulates X-Linked Inhibitor of Apoptosis Protein (XIAP)  

Microsoft Academic Search

BackgroundXIAP (X-linked inhibitor of apoptosis protein) is one of the most important members of the apoptosis inhibitor family. XIAP is upregulated in various malignancies, including human glioblastoma. It promotes invasion, metastasis, growth and survival of malignant cells. We hypothesized that downregulation of XIAP by human umbilical cord blood mesenchymal stem cells (hUCBSC) in glioma cells would cause them to undergo

Venkata Ramesh Dasari; Kiran Kumar Velpula; Kiranpreet Kaur; Daniel Fassett; Jeffrey D. Klopfenstein; Dzung H. Dinh; Meena Gujrati; Jasti S. Rao; Roger Chammas

2010-01-01

420

Resistance to fas-induced apoptosis in cells from human atherosclerotic lesions: elevated Bcl-XL inhibits apoptosis and caspase activation  

Microsoft Academic Search

The inappropriate survival of cells in the neointima contributes to atherosclerotic plaque progression, while apoptosis in the fibrous cap of lesions contributes to myocardial infarction and stroke. Prior genomic-scale transcript profiling of human carotid artery plaque cells with known sensitivity or resistance to fas-induced apoptosis identified candidate genes involved in lesion cell apoptosis. Retroviral overexpression indicated that several candidate factors

Zhaoqing Yang; Dmitry Gagarin; Ali Ramezani; Robert G. Hawley; Timothy A. McCaffrey

2007-01-01