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1

JIS Definition Identified More Malaysian Adults with Metabolic Syndrome Compared to the NCEP-ATP III and IDF Criteria  

PubMed Central

Metabolic syndrome (MetS) is a steering force for the cardiovascular diseases epidemic in Asia. This study aimed to compare the prevalence of MetS in Malaysian adults using NCEP-ATP III, IDF, and JIS definitions, identify the demographic factors associated with MetS, and determine the level of agreement between these definitions. The analytic sample consisted of 8,836 adults aged ?30 years recruited at baseline in 2007–2011 from the Cardiovascular Risk Prevention Study (CRisPS), an ongoing, prospective cohort study involving 18 urban and 22 rural communities in Malaysia. JIS definition gave the highest overall prevalence (43.4%) compared to NCEP-ATP III (26.5%) and IDF (37.4%), P < 0.001. Indians had significantly higher age-adjusted prevalence compared to other ethnic groups across all MetS definitions (30.1% by NCEP-ATP III, 50.8% by IDF, and 56.5% by JIS). The likelihood of having MetS amongst the rural and urban populations was similar across all definitions. A high level of agreement between the IDF and JIS was observed (Kappa index = 0.867), while there was a lower level of agreement between the IDF and NCEP-ATP III (Kappa index = 0.580). JIS definition identified more Malaysian adults with MetS and therefore should be recommended as the preferred diagnostic criterion.

Daher, Aqil Mohammad; Noor Khan Nor-Ashikin, Mohamed; Mat-Nasir, Nafiza; Keat Ng, Kien; Ambigga, Krishnapillai S.; Ariffin, Farnaza; Yasin Mazapuspavina, Md; Abdul-Razak, Suraya; Abdul-Hamid, Hasidah; Abd-Majid, Fadhlina; Abu-Bakar, Najmin; Nawawi, Hapizah; Yusoff, Khalid

2013-01-01

2

Metabolic syndrome in urban Asian Indian adults—a population study using modified ATP III criteria  

Microsoft Academic Search

Aims\\/hypothesis: To determine the prevalence of the Metabolic syndrome (MetS) using modified ATP III criteria in urban Asian Indian adults. Methods: 475 subjects (age 20–75 years) from a population data base were studied for the MetS using ATP III criteria but with a modified waist circumference (WC) appropriate for Indians. Presence of?3 of the following; raised WC (Men?90 cm, Women?85

A. Ramachandran; C. Snehalatha; K. Satyavani; S. Sivasankari; V. Vijay

2003-01-01

3

Journey in guidelines for lipid management: From adult treatment panel (ATP)-I to ATP-III and what to expect in ATP-IV  

PubMed Central

Adult Treatment Panel (ATP), an expert panel to supervise cholesterol management was set up under the aegis of National Cholesterol Education Program (NCEP) in 1985. Since then NCEP-ATP has been revising and framing guidelines to enable clinician to deliver better treatment to cardiovascular patients and to educate general people. As a result, considerable reduction in cardiovascular related deaths has been observed in recent times. All three ATP guidelines viz. ATP-I, ATP-II and ATP-III have targeted low density lipoprotein as their primary goal. The ATP-III guideline was updated in the light of evidences from 5-major clinical trials and was released in 2004. It added therapeutic lifestyle changes, concept of risk equivalents, Framingham CHD-risk score non-high density lipoprotein cholesterol (non-HDL-C) as secondary target and gave strong emphasis on metabolic risk factors. The earlier treat-to-target paradigm faced fierce criticism from clinicians across the globe because of insufficient proof of safety and benefits of treating patients with respect to an individual's low density lipoprotein (LDL) level. Further, demonstration of non-HDL-C and total cholesterol/HDL-C ratio as strong predictors of overall cardiovascular risk foresees new guidelines. A tailored-treatment approach was suggested instead of LDL-C target based treatment approach which was soundly based on direct clinical trials evidences and proposes treatment based on individual's overall 5- to 10-year cardiovascular risk irrespective of LDL-C level, leading to lower number of people on high dose/s of statins. Recent report of the Cholesterol Treatment Trialist's Collaborators meta-analysis strongly supported primary prevention of LDL with statins in low risk individuals and showed that its benefits completely outweighed its known hazards. Markers other than LDL-C like apolipoprotein B, non-HDL-C and total cholesterol/HDL-C ratio would take precedence in the risk assessment and strong emphasis would be given on tailored-treatment approach in the upcoming ATP-IV guideline.

Talwalkar, P. G.; Sreenivas, C. G.; Gulati, Ashish; Baxi, Hemang

2013-01-01

4

Journey in guidelines for lipid management: From adult treatment panel (ATP)-I to ATP-III and what to expect in ATP-IV.  

PubMed

Adult Treatment Panel (ATP), an expert panel to supervise cholesterol management was set up under the aegis of National Cholesterol Education Program (NCEP) in 1985. Since then NCEP-ATP has been revising and framing guidelines to enable clinician to deliver better treatment to cardiovascular patients and to educate general people. As a result, considerable reduction in cardiovascular related deaths has been observed in recent times. All three ATP guidelines viz. ATP-I, ATP-II and ATP-III have targeted low density lipoprotein as their primary goal. The ATP-III guideline was updated in the light of evidences from 5-major clinical trials and was released in 2004. It added therapeutic lifestyle changes, concept of risk equivalents, Framingham CHD-risk score non-high density lipoprotein cholesterol (non-HDL-C) as secondary target and gave strong emphasis on metabolic risk factors. The earlier treat-to-target paradigm faced fierce criticism from clinicians across the globe because of insufficient proof of safety and benefits of treating patients with respect to an individual's low density lipoprotein (LDL) level. Further, demonstration of non-HDL-C and total cholesterol/HDL-C ratio as strong predictors of overall cardiovascular risk foresees new guidelines. A tailored-treatment approach was suggested instead of LDL-C target based treatment approach which was soundly based on direct clinical trials evidences and proposes treatment based on individual's overall 5- to 10-year cardiovascular risk irrespective of LDL-C level, leading to lower number of people on high dose/s of statins. Recent report of the Cholesterol Treatment Trialist's Collaborators meta-analysis strongly supported primary prevention of LDL with statins in low risk individuals and showed that its benefits completely outweighed its known hazards. Markers other than LDL-C like apolipoprotein B, non-HDL-C and total cholesterol/HDL-C ratio would take precedence in the risk assessment and strong emphasis would be given on tailored-treatment approach in the upcoming ATP-IV guideline. PMID:23961478

Talwalkar, P G; Sreenivas, C G; Gulati, Ashish; Baxi, Hemang

2013-07-01

5

A sex caused inconsistency in DSM-III-R: the definition of mental disorder and the definition of paraphilias.  

PubMed

The DSM-III-R definition of mental disorder is inconsistent with the DSM-III-R definition of paraphilias. The former requires the suffering or increased risk of suffering some harm while the latter allows that deviance, by itself, is sufficient to classify a behavioral syndrome as a paraphilia. This inconsistency is particularly clear when examining the DSM-III-R account of a specific paraphilia, Transvestic Fetishism. The author defends the DSM-III-R definition of mental disorder and argues that the DSM-III-R definition of paraphilias should be changed. He recommends that the diagnostic criteria for specific paraphilias, particularly that for Transvestic Fetishism, be changed to make them consistent with the DSM-III-R definition of mental disorder. PMID:1588242

Gert, B

1992-04-01

6

Inhibition of the Fe(III)-Catalyzed Dopamine Oxidation by ATP and Its Relevance to Oxidative Stress in Parkinson's Disease.  

PubMed

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic cells, which implicates a role of dopamine (DA) in the etiology of PD. A possible DA degradation pathway is the Fe(III)-catalyzed oxidation of DA by oxygen, which produces neuronal toxins as side products. We investigated how ATP, an abundant and ubiquitous molecule in cellular milieu, affects the catalytic oxidation reaction of dopamine. For the first time, a unique, highly stable DA-Fe(III)-ATP ternary complex was formed and characterized in vitro. ATP as a ligand shifts the catecholate-Fe(III) ligand metal charge transfer (LMCT) band to a longer wavelength and the redox potentials of both DA and the Fe(III) center in the ternary complex. Remarkably, the additional ligation by ATP was found to significantly reverse the catalytic effect of the Fe(III) center on the DA oxidation. The reversal is attributed to the full occupation of the Fe(III) coordination sites by ATP and DA, which blocks O2 from accessing the Fe(III) center and its further reaction with DA. The biological relevance of this complex is strongly implicated by the identification of the ternary complex in the substantia nigra of rat brain and its attenuation of cytotoxicity of the Fe(III)-DA complex. Since ATP deficiency accompanies PD and neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) induced PD, deficiency of ATP and the resultant impairment toward the inhibition of the Fe(III)-catalyzed DA oxidation may contribute to the pathogenesis of PD. Our finding provides new insight into the pathways of DA oxidation and its relationship with synaptic activity. PMID:23823941

Jiang, Dianlu; Shi, Shuyun; Zhang, Lin; Liu, Lin; Ding, Bingrong; Zhao, Bingqing; Yagnik, Gargey; Zhou, Feimeng

2013-07-17

7

The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) prevalence of the metabolic syndrome in a Chinese population  

Microsoft Academic Search

To assess the prevalence of the metabolic syndrome disease cluster in the Hong Kong Chinese population we applied the US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) guidelines. This was present if ?3 of the following conditions were present: Hypertension (?130\\/85mmHg); fasting plasma glucose was ?6.1mmol\\/L; fasting plasma triglycerides ?1.69mmol\\/L; fasting HDL-cholesterol <1.04 or <1.29mmol in

G. Neil Thomas; Sai-Yin Ho; Edward D. Janus; Karen S. L. Lam; Anthony J. Hedley; Tai Hing Lam

2005-01-01

8

Compensatory upregulation of respiratory chain complexes III and IV in isolated deficiency of ATP synthase due to TMEM70 mutation.  

PubMed

Early onset mitochondrial encephalo-cardiomyopathy due to isolated deficiency of ATP synthase is frequently caused by mutations in TMEM70 gene encoding enzyme-specific ancillary factor. Diminished ATP synthase results in low ATP production, elevated mitochondrial membrane potential and increased ROS production. To test whether the patient cells may react to metabolic disbalance by changes in oxidative phosphorylation system, we performed a quantitative analysis of respiratory chain complexes and intramitochondrial proteases involved in their turnover. SDS- and BN-PAGE Western blot analysis of fibroblasts from 10 patients with TMEM70 317-2A>G homozygous mutation showed a significant 82-89% decrease of ATP synthase and 50-162% increase of respiratory chain complex IV and 22-53% increase of complex III. The content of Lon protease, paraplegin and prohibitins 1 and 2 was not significantly changed. Whole genome expression profiling revealed a generalized upregulation of transcriptional activity, but did not show any consistent changes in mRNA levels of structural subunits, specific assembly factors of respiratory chain complexes, or in regulatory genes of mitochondrial biogenesis which would parallel the protein data. The mtDNA content in patient cells was also not changed. The results indicate involvement of posttranscriptional events in the adaptive regulation of mitochondrial biogenesis that allows for the compensatory increase of respiratory chain complexes III and IV in response to deficiency of ATP synthase. PMID:22433607

Havlí?ková Karbanová, Vendula; Cížková Vrbacká, Alena; Hejzlarová, Kate?ina; N?sková, Hana; Stránecký, Viktor; Potocká, Andrea; Kmoch, Stanislav; Houšt?k, Josef

2012-03-10

9

Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis.  

PubMed

Disturbed endochondral ossification in X-linked hypophosphatemia indicates an involvement of P(i) in chondrogenesis. We studied the role of the sodium-dependent P(i) cotransporters (NPT), which are a widely recognized regulator of cellular P(i) homeostasis, and the downstream events in chondrogenesis using Hyp mice, the murine homolog of human X-linked hypophosphatemia. Hyp mice showed reduced apoptosis and mineralization in hypertrophic cartilage. Hyp chondrocytes in culture displayed decreased apoptosis and mineralization compared with WT chondrocytes, whereas glycosaminoglycan synthesis, an early event in chondrogenesis, was not altered. Expression of the type III NPT Pit-1 and P(i) uptake were diminished, and intracellular ATP levels were also reduced in parallel with decreased caspase-9 and caspase-3 activity in Hyp chondrocytes. The competitive NPT inhibitor phosphonoformic acid and ATP synthesis inhibitor 3-bromopyruvate disturbed endochondral ossification with reduced apoptosis in vivo and suppressed apoptosis and mineralization in conjunction with reduced P(i) uptake and ATP synthesis in WT chondrocytes. Overexpression of Pit-1 in Hyp chondrocytes reversed P(i) uptake and ATP synthesis and restored apoptosis and mineralization. Our results suggest that cellular ATP synthesis consequent to P(i) uptake via Pit-1 plays an important role in chondrocyte apoptosis and mineralization, and that chondrogenesis is ATP-dependent. PMID:21075853

Sugita, Atsushi; Kawai, Shinji; Hayashibara, Tetsuyuki; Amano, Atsuo; Ooshima, Takashi; Michigami, Toshimi; Yoshikawa, Hideki; Yoneda, Toshiyuki

2010-11-12

10

Iron(III)hydroxamate transport of Escherichia coli K12: Single amino acid replacements at potential ATP-binding sites inactivate the FhuC protein  

Microsoft Academic Search

The mechanism of iron(III)hydroxamate transport appears to be of the periplasmic binding protein dependent transport (PBT) kind which is energized by ATP hydrolysis. The FhuC protein contains two domains typical of ATP-binding proteins. Lysine in domain I was replaced by glutamine and glutamate, and aspartate in domain II by asparagine and glutamate, resulting in FhuC derivatives which no longer transported

Karin Becker; Wolfgang Köster; Volkmar Braun

1990-01-01

11

National Cholesterol Education Program Adult Treatment Panel III Versus International Diabetic Federation Definition of Metabolic Syndrome, Which One is Associated with Diabetes Mellitus and Coronary Artery Disease?  

PubMed Central

Background: A cluster of risk factors for cardiovascular diseases and type 2 diabetes mellitus, which occur together more often than by chance alone, have been known as the metabolic syndrome. Various definitions have been proposed by different organizations over the past decade. This study was designed to evaluate a new definition of the metabolic syndrome for the prediction of diabetes mellitus among the Iranian population. Methods: This study was carried out in an urban population, aged 20 to 74 years, from Yazd, a city in the center of Iran. The study is a part of the phase I of Yazd Healthy Heart Program, that is, a community-based intervention study for the prevention of cardiovascular disease. The significance level has been defined as P<0.05. Results: Prevalence of the metabolic syndrome by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria was 21.3 ± .017%, and by International Diabetes Federation (IDF) criteria it was 30.16 ± .02%. The multivariate analysis showed that the most important relevant factors of diabetes mellitus were: Increased age and metabolic syndrome by both definitions of NCEP and IDF criteria, and also, the most important relevant factors of stable angina were: Increased age, male sex, and metabolic syndrome by only IDF definitions, but the NCEP definition of the metabolic syndrome cannot predict diabetes mellitus independent of age and sex. Conclusion: This study showed that increased age and metabolic syndrome are the most important relevant factors for diabetes mellitus, especially by using the IDF criteria for definition of the metabolic syndrome.

Rezaianzadeh, Abbas; Namayandeh, Seyedeh-Mahdieh; Sadr, Seyed-Mahmood

2012-01-01

12

Spermatogonia of rainbow trout: III. In vitro study of the proliferative response to extracellular ATP and adenosine.  

PubMed

Unlike in higher vertebrates, in fish it is not known whether the nerve supply of the testis can influence testicular functions or not. In addition to neurotransmitters, nerve terminals may release ATP and adenosine in the extracellular medium. On the assumption that these molecules might be released by fibers innervating the teleost testis, it is possible that they participate in the control of testicular function and, maybe, in the control of spermatogonia (Go) proliferation. This study addresses this issue. We have investigated the ability for extracellular ATP and adenosine to influence the in vitro incorporation, either basal or GTH-, IGF-I- and suramin-stimulated, of 3H-thymidine (3H-Tdr) by trout Go. Mixed suspensions of somatic and germ cells prepared from testes, which were immature or spermatogenetic, were cultured usually for 4.5 days in the presence or not of the tested molecules; 3H-Tdr was added during the last day in culture. In our cell culture conditions, 25 to 250 microM adenosine, ATP, ADP, and AMP stimulated the 3H-Tdr incorporation by Go from prespermatogenetic testes and from testes starting spermatogenesis, in a dose-dependent way. The effect of these molecules decreased when the testes were more advanced in spermatogenesis and it became inhibiting when the testes were in mid-spermatogenesis. Five'-N-ethylcarboxamidoadenosine (NECA) was as potent as adenosine in stimulating or inhibiting 3H-Tdr incorporation, while R-N6-(2-phenylisopropyl)adenosine (R-PIA) always had a marked inhibiting effect. Adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS; 25-200 microM), a non-hydrolysable analogue of ATP, which had no effect on Go from prespermatogenetic testes (collected October-February) and from testes in advanced spermatogenesis, stimulated 3H-Tdr incorporation by Go from testes at the beginning of spermatogenesis very efficiently. The order of potency of the different ATP analogues was as follows: ATPgammaS > ATP congruent with alpha,beta-methylene-ATP > UTP > 2-methylthio-ATP. These data suggest that A2 adenosine receptors and P2 receptors would be present on unidentified testicular cells. The stimulating effect of adenosine/ATP was additive with that of either GTH-I or IGF-I or suramin when the cells were from testes at the beginning of spermatogenesis, but adenosine suppressed their effect when the cells were from testes in mid-spermatogenesis. In conclusion, our results suggest that in the trout extracellular adenosine and ATP are able to influence the in vitro proliferation of Go, and are potential candidates for mediating the possible influence of the nervous system on the induction, speeding up, then slowing down of spermatogenesis. PMID:10398420

Loir, M

1999-08-01

13

In vitro study of accuracy of cervical pedicle screw insertion using an electronic conductivity device (ATPS part III)  

Microsoft Academic Search

Reconstruction of the highly unstable, anteriorly decompressed cervical spine poses biomechanical challenges to current stabilization\\u000a strategies, including circumferential instrumented fusion, to prevent failure. To avoid secondary posterior surgery, particularly\\u000a in the elderly population, while increasing primary construct rigidity of anterior-only reconstructions, the authors introduced\\u000a the concept of anterior transpedicular screw (ATPS) fixation and plating. We demonstrated its morphological feasibility, its

Heiko Koller; Wolfgang Hitzl; Frank Acosta; Mark Tauber; Juliane Zenner; Herbert Resch; Yasutsugu Yukawa; Oliver Meier; Rene Schmidt; Michael Mayer

2009-01-01

14

Metabolic syndrome according to different definitions in a rapidly developing country of the African region  

Microsoft Academic Search

AIMS: We examined, in a country of the African region, i) the prevalence of the metabolic syndrome (MetS) according to three definitions (ATP, WHO and IDF); ii) the distribution of the MetS criteria; iii) the level of agreement between these three definitions and iv) we also examined these issues upon exclusion of people with diabetes. METHODS: We conducted an examination

Clara Kelliny; Julita William; Walter Riesen; Fred Paccaud; Pascal Bovet

2008-01-01

15

Prevalence of Metabolic Syndrome among Malaysians using the International Diabetes Federation, National Cholesterol Education Program and Modified World Health Organization Definitions  

Microsoft Academic Search

The World Health Organization (WHO), National Cholesterol Education Program Adults Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) have proposed different criteria to diagnose metabolic syndrome (MetS). However, there is no single definition to accurately diagnose MetS. The objective of this study is to estimate the prevalence of MetS using WHO, NCEP ATP III and IDF in

Bee Ying Tan; Haresh Kumar Kantilal; Rajbans Singh

16

Complexation of bisphosphonates with Ytterbium(III): Application of phosphate and ATP detection assay based on Yb3+-pyrocatechol violet  

PubMed Central

The coordination chemistry of bisphosphonates with Yb3+ was investigated to evaluate the potential of the UV-Vis based detection method using the Yb3+-pyrocatechol complexation reaction as a sensor for bisphosphonates. The complexation chemistry of Yb3+ with phosphate and ATP analogs was previously described (E. Gaidamauskas et al J. Biol. Inorg. Chem. 13 (2008) 1291-1299), and we here study the complexation chemistry of bisphosphonates in this system. The spectrophotometric assay yields direct evidence for formation of a 4:3 metal to ligand complex at neutral pH. Direct evidence for Yb3+ : methylenebis(phosphonate) complexes with 1:1 and 1:2 stoichiometry was also obtained by potentiometry at acidic and basic pH. Direct evidence for complex formation was obtained using 1H NMR spectroscopy although the stoichiometry was not accessed at neutral pH. Our results suggest that the spectroscopic observation of the YbPV complex can be used to conveniently measure concentrations of bisphosphonates down to 2-3 ?M .

Gaidamauskas, Ernestas; Parker, Helen; Kashemirov, Boris A.; Holder, Alvin A.; Saejueng, Kanokkarn; McKenna, Charles E.; Crans, Debbie C.

2009-01-01

17

Complexation of bisphosphonates with ytterbium(III): application of phosphate and ATP detection assay based on Yb(3+)-pyrocatechol violet.  

PubMed

The coordination chemistry of bisphosphonates with Yb(3+) was investigated to evaluate the potential of the UV-vis based detection method using the Yb(3+)-pyrocatechol complexation reaction as a sensor for bisphosphonates. The complexation chemistry of Yb(3+) with phosphate and ATP analogs was previously described (E. Gaidamauskas, K. Saejueng, A.A. Holder, S. Bharuah, B.A. Kashemirov, D.C. Crans, C.E. McKenna, J. Biol. Inorg. Chem. 13 (2008) 1291-1299), and we here studied the complexation chemistry of bisphosphonates in this system. The spectrophotometric assay yields direct evidence for formation of a 4:3 metal to ligand complex at neutral pH. Direct evidence for Yb(3+):methylenebis(phosphonate) complexes with 1:1 and 1:2 stoichiometry was also obtained by potentiometry at acidic and basic pH. Direct evidence for complex formation was obtained using (1)H NMR spectroscopy although the stoichiometry was not accessed at neutral pH. Our results suggest that the spectroscopic observation of the YbPV complex can be used to conveniently measure concentrations of bisphosphonates down to 2-3 microM. PMID:19850352

Gaidamauskas, Ernestas; Parker, Helen; Kashemirov, Boris A; Holder, Alvin A; Saejueng, Kanokkarn; McKenna, Charles E; Crans, Debbie C

2009-09-20

18

15 CFR 295.2 - Definitions.  

Code of Federal Regulations, 2013 CFR

...Definitions. (a) For the purposes of the ATP, the term award means Federal financial...include salaries of personnel working on the ATP project and associated reasonable fringe...equipment required specifically for the ATP project, and travel associated with...

2013-01-01

19

15 CFR 295.2 - Definitions.  

Code of Federal Regulations, 2012 CFR

...Definitions. (a) For the purposes of the ATP, the term award means Federal financial...include salaries of personnel working on the ATP project and associated reasonable fringe...equipment required specifically for the ATP project, and travel associated with...

2012-01-01

20

Mark III LOCA-Related Hydrodynamic Load Definition. Generic Technical Activity B-10.  

National Technical Information Service (NTIS)

This report provides a discussion of LOCA-related suppression pool hydrodynamic loads in boiling water reactor (BWR) facilities with the Mark III pressure-suppression containment design. On the basis of certain large-scale tests conducted between 1973 and...

M. B. Fields J. A. Kudrick

1984-01-01

21

Understanding radio polarimetry. III. Interpreting the IAU/IEEE definitions of the Stokes parameters.  

NASA Astrophysics Data System (ADS)

In two companion papers (Paper I, Hamaker et al. 1996; Paper II, Sault et al. 1996), a new theory of radio-interferometric polarimetry and its application to the calibration of interferometer arrays are presented. To complete our study of radio polarimetry, we examine here the definition of the Stokes parameters adopted by Commission 40 of the IAU (1974) and the way this definition works out in the mathematical equations. Using the formalism of Paper I, we give a simplified derivation of the frequently-cited `black-box' formula originally derived by Morris et al. (1964). We show that their original version is in error in the sign of Stokes V, the correct sign being that given by Weiler (1973) and Thompson et al. (1986).

Hamaker, J. P.; Bregman, J. D.

1996-05-01

22

ATP utilization by yeast replication factor C. III. The ATP-binding domains of Rfc2, Rfc3, and Rfc4 are essential for DNA recognition and clamp loading.  

PubMed

The conserved lysine in the Walker A motif of the ATP-binding domain encoded by the yeast RFC1, RFC2, RFC3, and RFC4 genes was mutated to glutamic acid. Complexes of replication factor C with a N-terminal truncation (Delta2-273) of the Rfc1 subunit (RFC) containing a single mutant subunit were overproduced in Escherichia coli for biochemical analysis. All of the mutant RFC complexes were capable of interacting with PCNA. Complexes containing a rfc1-K359E mutation were similar to wild type in replication activity and ATPase activity; however, the mutant complex showed increased susceptibility to proteolysis. In contrast, complexes containing either a rfc2-K71E mutation or a rfc3-K59E mutation were severely impaired in ATPase and clamp loading activity. In addition to their defects in ATP hydrolysis, these complexes were defective for DNA binding. A mutant complex containing the rfc4-K55E mutation performed as well as a wild type complex in clamp loading, but only at very high ATP concentrations. Mutant RFC complexes containing rfc2-K71R or rfc3-K59R, carrying a conservative lysine --> arginine mutation, had much milder clamp loading defects that could be partially (rfc2-K71R) or completely (rfc3-K59R) suppressed at high ATP concentrations. PMID:11432854

Schmidt, S L; Gomes, X V; Burgers, P M

2001-06-29

23

Functional dyspepsia--symptoms, definitions and validity of the Rome III criteria.  

PubMed

Dyspepsia refers to a heterogeneous group of symptoms that are localized in the epigastric region. Typical dyspeptic symptoms include postprandial fullness, early satiation, epigastric pain and epigastric burning, but other upper gastrointestinal symptoms such as nausea, belching or abdominal bloating often occur. Functional dyspepsia is defined as the presence of dyspeptic symptoms in the absence of an organic cause that readily explains them. The Rome III consensus proposed the subdivision of functional dyspepsia into postprandial distress syndrome (PDS), characterized by postprandial fullness and early satiation, and epigastric pain syndrome (EPS), characterized by epigastric pain or burning. Epidemiological studies in the USA and Europe confirmed the presence of both subgroups, with good separation between EPS and PDS. By contrast, other studies have found major overlap between EPS and PDS in patients with functional dyspepsia in specialist care centres in Europe and Asia. Preliminary pathophysiological studies suggest that PDS might be characterized by a higher prevalence of impaired gastric accommodation than EPS and raised duodenal eosinophil counts. Whether different treatment approaches are needed for EPS and PDS is currently unclear; only acotiamide, a new drug for the treatment of functional dyspepsia, has been found to be efficacious in PDS but not in EPS. Further randomized controlled trials testing treatment response by subgroup are urgently needed. PMID:23399526

Tack, Jan; Talley, Nicholas J

2013-02-12

24

Feasibility of endoscopic mucosal resection as salvage treatment for patients with local failure after definitive chemoradiotherapy for stage IB, II, and III esophageal squamous cell cancer.  

PubMed

Local failure after definitive chemoradiotherapy (CRT) for stage IB, II, and III esophageal cancer is one of the causes of poor outcome. Endoscopic mucosal resection (EMR) is an effective treatment for superficial esophageal cancer. However, its feasibility as a salvage treatment for local recurrent or residual tumors after definitive CRT for stage IB, II, and III esophageal cancer remains unclear. Between January 2000 and February 2008, 274 patients with stage IB, II, and III esophageal squamous cell cancer excluding T4 received definitive CRT at the National Cancer Center Hospital, Japan. Of these patients, nine patients with local recurrence after achieving complete response and two patients with residual tumor underwent salvage EMR. The technique of salvage EMR involved a strip biopsy method. We retrospectively reviewed the 11 patients (13 lesions). Characteristics of all 11 patients were as follows: median age of 69 (range: 45-78); male/female: 10/1; baseline clinical stage (Union for International Cancer Control 7th) IB/IIA/IIB/III: 1/3/7/0. The depth of resected tumor was limited to the mucosal layer in seven lesions and submucosal in six lesions. En bloc resection was performed on six lesions (46%). The vertical margin was free of cancer cells in 11 lesions (84.6%). No major complications, such as hemorrhage requiring blood transfusion and perforation, were experienced. At a median follow-up period of 38.9 months (range: 5.3-94 months) after salvage EMR, no recurrence was detected in six patients (54%). Local recurrence was detected in five patients (27%). Of these patients, two had lung metastasis simultaneously, and one was also detected lung metastasis 2 months after the detection of local recurrence. The 5-year survival rate after salvage EMR was 41.6%. Salvage EMR is a feasible treatment option for local recurrent or residual lesions after definitive chemotherapy and/or radiotherapy for stage IB, II, and III esophageal squamous cell cancer. PMID:23442160

Makazu, M; Kato, K; Takisawa, H; Yoshinaga, S; Oda, I; Saito, Y; Mayahara, H; Ito, Y; Itami, J; Hamaguchi, T; Yamada, Y; Shimada, Y

2013-02-26

25

Stages III and IV Squamous Cell Carcinoma of the Mouth: Three-Year Experience with Superselective Intraarterial Chemotherapy Using Cisplatin Prior to Definitive Treatment  

Microsoft Academic Search

Purpose: This study was designed to assess the 3-year experience with superselective intraarterial chemotherapy prior to definitive treatment for stages III and IV squamous cell carcinomas of the mouth. Methods: Twenty-two patients prospectively received superselective intraarterial chemotherapy using relatively low-dose cisplatin via a transfemoral approach. The locations of the tumors were the tongue (n= 12), gingiva (n= 5), buccal mucosa

Toshinori Hirai; Yukunori Korogi; Satoshi Hamatake; Ryuichi Nishimura; Yuji Baba; Mutsumasa Takahashi; Yasuyoshi Uji; Akira Taen

1999-01-01

26

Opening of the mitoK ATP channel and decoupling of mitochondrial complex II and III contribute to the suppression of myocardial reperfusion hyperoxygenation  

Microsoft Academic Search

Diazoxide, a mitochondrial ATP-sensitive potassium (mitoKATP) channel opener, protects the heart from ischemia–reperfusion injury. Diazoxide also inhibits mitochondrial complex II-dependent\\u000a respiration in addition to its preconditioning effect. However, there are no prior studies of the role of diazoxide on post-ischemic\\u000a myocardial oxygenation. In the current study, we determined the effect of diazoxide on the suppression of post-ischemic myocardial\\u000a tissue hyperoxygenation

Bin Liu; Xuehai Zhu; Chwen-Lih Chen; Keli Hu; Harold M. Swartz; Yeong-Renn Chen; Guanglong He

2010-01-01

27

Making ATP  

PubMed Central

We present a mesoscopic model for ATP synthesis by F1Fo ATPase. The model combines the existing experimental knowledge of the F1 enzyme into a consistent mathematical model that illuminates how the stages in synthesis are related to the protein structure. For example, the model illuminates how specific interactions between the ?, ?, and ?3?3 subunits couple the Fo motor to events at the catalytic sites. The model also elucidates the origin of ADP inhibition of F1 in its hydrolysis mode. The methodology we develop for constructing the structure-based model should prove useful in modeling other protein motors.

Xing, Jianhua; Liao, Jung-Chi; Oster, George

2005-01-01

28

The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy  

SciTech Connect

Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC patients treated with definitive radiotherapy are distinct from those observed in patients who undergo surgical resection. The ultimate efficacy of radiation in locally advanced NSCLC is dependent on the intrinsic biology of the tumor.

Fernandes, Annemarie T. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Xanthopoulos, Eric [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Evans, Tracey; Stevenson, James; Langer, Corey [Department of Medical Oncology, University of Pennsylvania, Philadelphia, PA (United States); Kucharczuk, John C. [Department of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA (United States); Lin, Lilie; Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

2012-05-01

29

Stages III and IV squamous cell carcinoma of the mouth: Three-year experience with superselective intraarterial chemotherapy using cisplatin prior to definitive treatment  

Microsoft Academic Search

Purpose: This study was designed to assess the 3-year experience with superselective intraarterial chemotherapy prior to definitive\\u000a treatment for stages III and IV squamous cell carcinomas of the mouth.\\u000a \\u000a \\u000a Methods: Twenty-two patients prospectively received superselective intraarterial chemotherapy using relatively low-dose cisplatin\\u000a via a transfemoral approach. The locations of the tumors were the tongue (n=12), gingiva (n=5), buccal mucosa (n=2), hard

Toshinori Hirai; Yukunori Korogi; Satoshi Hamatake; Ryuichi Nishimura; Yuji Baba; Mutsumasa Takahashi; Yasuyoshi Uji; Akira Taen

1999-01-01

30

Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma—long-term results of phase III RTOG 85–31  

Microsoft Academic Search

Purpose: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). Methods and Materials: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy

Miljenko V.. Pilepich; Kathryn Winter; Colleen A. Lawton; Robert E. Krisch; Harvey B. Wolkov; Benjamin Movsas; Eugen B. Hug; Sucha O. Asbell; David Grignon

2005-01-01

31

Cx43 hemichannels are permeable to ATP  

PubMed Central

Astrocytes are electrically non-excitable cells that communicate by means of Ca2+ signaling. Long-distance intercellular Ca2+ waves are initiated by release of ATP and activation of purinergic receptors on nearby cells. Previous studies have implicated connexin 43 (Cx43) in ATP release, but definitive proof that ATP exits through Cx43 hemichannels does not exist. Here we show that ATP anions can permeate through Cx43 hemichannels using several alternative approaches. First, openings of Cx43 hemichannels were detected in both cell-attached and inside-out patch recordings in C6 cells expressing Cx43, but not in C6 cells expressing Cx43-eGFP (enhanced green fluorescent protein) or a C-terminus truncation mutant of Cx43. Second, Cx43 hemichannel openings were inhibited by three structurally different gap-junction channel blockers, but not by the P2X7 blocker Brilliant blue G. Third, bioluminescence imaging of ATP combined with single channel recording in the inside-out patch configuration showed that ATP efflux coincided with channel openings and was absent when the Cx43 hemichannel was closed. Fourth, ion replacement experiments confirmed that Cx43 hemichannels are permeable to ATP. In sum, these observations provide the first direct evidence for efflux of ATP through Cx43 hemichannels. Furthermore, a putative Cx43 hemichannel with characteristics identical to the Cx43 hemichannel in C6 cells was identified in the membrane of hippocampal astrocytes in acutely prepared slices.

Kang, Jian; Kang, Ning; Lovatt, Ditte; Torres, Arnulfo; Zhao, Zhuo; Lin, Jane; Nedergaard, Maiken

2013-01-01

32

Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma-long-term results of phase III RTOG 85-31  

SciTech Connect

Purpose: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). Methods and Materials: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression. Results: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm. Conclusion: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.

Pilepich, Miljenko V. [University of California, Los Angeles, School of Medicine, Los Angeles, CA (United States)]. E-mail: mpilepich@mednet.ucla.edu; Winter, Kathryn [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Lawton, Colleen A. [Medical College of Wisconsin, Milwaukee, WI (United States); Krisch, Robert E. [University of Pennsylvania, Philadelphia, PA (United States); Wolkov, Harvey B. [Radiology Associates of Sacramento, Sacramento, CA (United States); Movsas, Benjamin [Fox Chase Cancer Center, Philadelphia, PA (United States); Hug, Eugen B. [Dartmouth Hitchcock Medical Center, Lebanon, NH (United States); Asbell, Sucha O. [Albert Einstein Medical Center, Philadelphia, PA (United States); Grignon, David [Wayne State University, Detroit, MI (United States)

2005-04-01

33

ATP synthesis and storage.  

PubMed

Since 1929, when it was discovered that ATP is a substrate for muscle contraction, the knowledge about this purine nucleotide has been greatly expanded. Many aspects of cell metabolism revolve around ATP production and consumption. It is important to understand the concepts of glucose and oxygen consumption in aerobic and anaerobic life and to link bioenergetics with the vast amount of reactions occurring within cells. ATP is universally seen as the energy exchange factor that connects anabolism and catabolism but also fuels processes such as motile contraction, phosphorylations, and active transport. It is also a signalling molecule in the purinergic signalling mechanisms. In this review, we will discuss all the main mechanisms of ATP production linked to ADP phosphorylation as well the regulation of these mechanisms during stress conditions and in connection with calcium signalling events. Recent advances regarding ATP storage and its special significance for purinergic signalling will also be reviewed. PMID:22528680

Bonora, Massimo; Patergnani, Simone; Rimessi, Alessandro; De Marchi, Elena; Suski, Jan M; Bononi, Angela; Giorgi, Carlotta; Marchi, Saverio; Missiroli, Sonia; Poletti, Federica; Wieckowski, Mariusz R; Pinton, Paolo

2012-04-12

34

Stages III and IV Squamous Cell Carcinoma of the Mouth: Three-Year Experience with Superselective Intraarterial Chemotherapy Using Cisplatin Prior to Definitive Treatment  

SciTech Connect

Purpose: This study was designed to assess the 3-year experience with superselective intraarterial chemotherapy prior to definitive treatment for stages III and IV squamous cell carcinomas of the mouth. Methods: Twenty-two patients prospectively received superselective intraarterial chemotherapy using relatively low-dose cisplatin via a transfemoral approach. The locations of the tumors were the tongue (n= 12), gingiva (n= 5), buccal mucosa (n= 2), hard palate (n= 1), floor of the mouth (n= 1), and lip (n= 1). After intraarterial chemotherapy, 21 patients underwent surgery (n= 14), radiation therapy (n= 6), or both (n= 1). The survival rate of 25 patients who underwent surgery with/without radiation therapy until 1992 at Kumamoto University Hospital was also evaluated as a historical control. The survival curve was calculated with the Kaplan-Meier method, and the statistical difference between survival curves was determined with the generalized Wilcoxon test. Results: The overall response rate was 95% [complete response (tumor completely resolved), 24%; partial response (tumor reduction {>=}50%), 71%]. Fifty-two intraarterial infusions were performed without any catheter-related complications. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. One patient died of renal failure from cisplatin. After a median follow-up of 20 months (range 2-41 months), the estimated 3-year survival rate for patients who underwent intraarterial chemotherapy plus surgery was 91%. The survival of the patients who underwent intraarterial chemotherapy plus surgery tended to be longer than that of the historical control. Conclusions: Early tumor reduction without delay of subsequent treatments can be obtained by intraarterial chemotherapy while minimizing complications and possibly improving survival. Further investigations of long-term survival with larger series need to be performed.

Hirai, Toshinori; Korogi, Yukunori; Hamatake, Satoshi; Nishimura, Ryuichi; Baba, Yuji; Takahashi, Mutsumasa [Department of Radiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860 (Japan); Uji, Yasuyoshi; Taen, Akira [Department of Oral and Maxillofacial Surgery, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860 (Japan)

1999-05-15

35

ATP signalling in epilepsy  

Microsoft Academic Search

This paper focuses on a role for ATP neurotransmission and gliotransmission in the pathophysiology of epileptic seizures.\\u000a ATP along with gap junctions propagates the glial calcium wave, which is an extraneuronal signalling pathway in the central\\u000a nervous system. Recently astrocyte intercellular calcium waves have been shown to underlie seizures, and conventional antiepileptic\\u000a drugs have been shown to attenuate these calcium

Ashwin Kumaria; Christos M. Tolias; Geoffrey Burnstock

2008-01-01

36

Metabolic syndrome in a sample of the 6- to 16-year-old overweight or obese pediatric population: a comparison of two definitions  

PubMed Central

Purpose The purpose of this study was to estimate the presence of metabolic syndrome (MS) in a group of children and adolescents with a body mass index (BMI) above the 85th percentile for their age and sex in Qazvin Province, Iran; to evaluate the relationship between obesity and metabolic abnormalities; and to compare two proposed definitions of MS. Patients and methods The study was conducted on 100 healthy subjects aged between 6 and 16 years (average age, 10.52 ± 2.51 years) with a high BMI for their age and sex. Fifty- eight percent of subjects were female. Physical examination including evaluation of weight, height, BMI, and blood pressure measurement was performed (“overweight” was defined as a BMI between the 85th and 95th percentiles for children of the same age and sex; “obese” was defined as a BMI over the 95th percentile for children of the same age and sex). Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and uric acid were measured after a 12-hour overnight fast. The authors used and compared two definitions of MS: the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) criteria and a modified definition by Weiss et al. Variables were compared using the Student’s t-test and chi-square and Mann-Whitney U tests, and agreement between the two definitions was analyzed using kappa values. Results The subjects had a mean BMI of 26.02 ± 4.38 and 80% had obesity. Insulin resistance was found in 81% of the study population. MS was present in ten (50%) of the overweight and 53 (66.2%) of the obese subjects using the NCEP ATP III criteria. MS was present in five (25%) of the overweight and 34 (42.5%) of the obese subjects using the definition by Weiss et al. The overall kappa value for the two definitions of MS was 0.533. There were no statistically significant differences between the two definitions of MS in participants. Conclusion The prevalence of MS in children and adolescents depends on the criteria chosen and their respective cutoff points. The NCEP ATP III criteria, the parameters of which include higher cutoff values for high-density lipoprotein cholesterol and triglycerides, detected the higher prevalence and therefore the NCEP ATP III criteria are able to diagnose a larger number of children and adolescents at metabolic risk.

Saffari, Fatemeh; Jalilolghadr, Shabnam; Esmailzadehha, Neda; Azinfar, Peyman

2012-01-01

37

A Review of the Definition and Measurement of Poverty: Volume I, Summary Review Paper; Volume II, Annotated Bibliography. The Measure of Poverty, Technical Paper III.  

ERIC Educational Resources Information Center

|This study reviews the existing literature on a series of issues associated with the defintion and measurement of poverty, and it consists of a summary report covering this research (Volume I), and an annotated bibliography (Volume II). Eleven specific issues were identified and reviewed in this study: (1) the historical definitions of poverty,…

Oster, Sharon; And Others

38

Optogenetic control of ATP release  

NASA Astrophysics Data System (ADS)

Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

2013-03-01

39

ATP7B (WND) protein  

Microsoft Academic Search

Wilson's disease is a genetic disorder of copper metabolism characterized by the excessive accumulation of this metal in the liver. The gene for Wilson's disease, designated ATP7B, encodes a copper transporting P-type ATPase expressed predominantly in the liver. Over 60 disease specific mutations of ATP7B have now been reported in patients with Wilson's disease. The gene for ATP7B is ?80

Kunihiko Terada; Michael L Schilsky; Naoyuki Miura; Toshihiro Sugiyama

1998-01-01

40

Microglia release ATP by exocytosis.  

PubMed

Microglia survey the brain environment by sensing several types of diffusible molecules, among which extracellular nucleotides released/leaked from damaged cells have central roles. Microglia sense ATP or other nucleotides by multiple P2 receptors, after which they change into several different phenotypes. However, so far, it is largely unknown whether microglia themselves release ATP and, if so, by what mechanism. Here we show that exocytosis is the mechanism by which microglia release ATP. When we stimulated microglia with ionomycin, they released ATP and the release was dependent on Ca²?, vesicular H?-ATPase, or SNAREs but independent of connexin/pannexin hemichannels. VNUT was found to be expressed in microglia and exhibited no colocalization with lysosome. We also visualized the exocytosis of ATP by a quinacrine-based fluorescent time-lapse imaging. Moreover, we found that lipopolysaccharide increased the ionomycin-induced release of ATP, which was dependent on the increase in VNUT. Taken together, our data suggested that exocytosis is the mechanism of ATP release from microglia. When activated, they would release ATP by increasing VNUT-dependent exocytotic mechanisms. PMID:23832620

Imura, Yoshio; Morizawa, Yosuke; Komatsu, Ryohei; Shibata, Keisuke; Shinozaki, Youichi; Kasai, Hirotake; Moriishi, Kohji; Moriyama, Yoshinori; Koizumi, Schuichi

2013-07-05

41

Structure of ATP-Bound Human ATP:Cobalamin Adenosyltransferase  

SciTech Connect

Mutations in the gene encoding human ATP:cobalamin adenosyltransferase (hATR) can result in the metabolic disorder known as methylmalonic aciduria (MMA). This enzyme catalyzes the final step in the conversion of cyanocobalamin (vitamin B{sub 12}) to the essential human cofactor adenosylcobalamin. Here we present the 2.5 {angstrom} crystal structure of ATP bound to hATR refined to an R{sub free} value of 25.2%. The enzyme forms a tightly associated trimer, where the monomer comprises a five-helix bundle and the active sites lie on the subunit interfaces. Only two of the three active sites within the trimer contain the bound ATP substrate, thereby providing examples of apo- and substrate-bound-active sites within the same crystal structure. Comparison of the empty and occupied sites indicates that twenty residues at the enzyme's N-terminus become ordered upon binding of ATP to form a novel ATP-binding site and an extended cleft that likely binds cobalamin. The structure explains the role of 20 invariant residues; six are involved in ATP binding, including Arg190, which hydrogen bonds to ATP atoms on both sides of the scissile bond. Ten of the hydrogen bonds are required for structural stability, and four are in positions to interact with cobalamin. The structure also reveals how the point mutations that cause MMA are deficient in these functions.

Schubert,H.; Hill, C.

2006-01-01

42

Structure of complex III with bound cytochrome c in reduced state and definition of a minimal core interface for electron transfer.  

PubMed

In cellular respiration, cytochrome c transfers electrons from cytochrome bc(1) complex (complex III) to cytochrome c oxidase by transiently binding to the membrane proteins. Here, we report the structure of isoform-1 cytochrome c bound to cytochrome bc(1) complex at 1.9 A resolution in reduced state. The dimer structure is asymmetric. Monovalent cytochrome c binding is correlated with conformational changes of the Rieske head domain and subunit QCR6p and with a higher number of interfacial water molecules bound to cytochrome c(1). Pronounced hydration and a "mobility mismatch" at the interface with disordered charged residues on the cytochrome c side are favorable for transient binding. Within the hydrophobic interface, a minimal core was identified by comparison with the novel structure of the complex with bound isoform-2 cytochrome c. Four core interactions encircle the heme cofactors surrounded by variable interactions. The core interface may be a feature to gain specificity for formation of the reactive complex. PMID:18390544

Solmaz, Sozanne R N; Hunte, Carola

2008-04-04

43

Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy  

PubMed Central

Background Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy). Methods We have studied, using monoclonal antibodies for immunohistochemistry, the Id1 and Id3 tumor epithelial expression in 17 patients with stage III-N2 non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy. Results Id1 expression is observed in 82.4% of the tumors, whereas Id3 expression is present in 41.2% of the samples. Interestingly, Id1 and Id3 expression are mutually correlated (R?=?0.579, p?=?0.015). In a subgroup analysis of patients with the most locally advanced disease (T4N2 stage), co-expression of Id1 and Id3 showed to be related with a worse overall survival (45 vs 6 months, p?=?0.002). A trend towards significance for a worse progression free survival (30 vs 1 months, p?=?0.219) and a lower response rate to the treatment (RR?=?50% vs 87.5%, p?=?0.07) were also observed. Conclusions A correlation between Id1 and Id3 protein expression is observed. Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced NSCLC treated with definitive chemoradiotherapy.

2013-01-01

44

ATP-dependent Chromatin Remodelling  

Microsoft Academic Search

Alterations of chromatin structure play an important role in gene regulation. One way of doing so involves ATP-dependent chromatin\\u000a remodelling enzymes that act as molecular machines coupling ATP-hydrolysis to structural changes of the nucleosome. Several\\u000a recent studies shed important insights into the mechanism of these factors and indicate that they couple DNA translocation\\u000a within the nucleosome to DNA loop propagation

Parul Choudhary; Patrick Varga-Weisz

45

Definitely Life but not Definitively  

Microsoft Academic Search

Although there have been attempts at a definition of life from many disciplines, none is accepted by all as definitive. Some\\u000a people believe that it is impossible to define ‘life’ adequately at the moment. We agree with this point of view on linguistic\\u000a grounds, examining the different types of definition, the contexts in which they are used and their relative

Joan D. Oliver; Randall S. Perry

2006-01-01

46

Energy transduction in ATP synthase  

NASA Astrophysics Data System (ADS)

Mitochondria, bacteria and chloroplasts use the free energy stored in transmembrane ion gradients to manufacture ATP by the action of ATP synthase. This enzyme consists of two principal domains. The asymmetric membrane-spanning Fo portion contains the proton channel, and the soluble F1 portion contains three catalytic sites which cooperate in the synthetic reactions. The flow of protons through Fo is thought to generate a torque which is transmitted to F1 by an asymmetric shaft, the coiled-coil ?-subunit. This acts as a rotating `cam' within F1, sequentially releasing ATPs from the three active sites. The free-energy difference across the inner membrane of mitochondria and bacteria is sufficient to produce three ATPs per twelve protons passing through the motor. It has been suggested that this protonmotive force biases the rotor's diffusion so that Fo constitutes a rotary motor turning the ? shaft. Here we show that biased diffusion, augmented by electrostatic forces, does indeed generate sufficient torque to account for ATP production. Moreover, the motor's reversibility - supplying torque from ATP hydrolysis in F1 converts the motor into an efficient proton pump - can also be explained by our model.

Elston, Timothy; Wang, Hongyun; Oster, George

1998-01-01

47

Extracellular ATP in plants. Visualization, localization, and analysis of physiological significance in growth and signaling.  

PubMed

Extracellular ATP (eATP) in animals is well documented and known to play an important role in cellular signaling (e.g. at the nerve synapse). The existence of eATP has been postulated in plants; however, there is no definitive experimental evidence for its presence or an explanation as to how such a polar molecule could exit the plant cell and what physiological role it may play in plant growth and development. The presence of eATP in plants (Medicago truncatula) was detected by constructing a novel reporter; i.e. fusing a cellulose-binding domain peptide to the ATP-requiring enzyme luciferase. Application of this reporter to plant roots allowed visualization of eATP in the presence of the substrate luciferin. Luciferase activity could be detected in the interstitial spaces between plant epidermal cells and predominantly at the regions of actively growing cells. The levels of eATP were closely correlated with regions of active growth and cell expansion. Pharmacological compounds known to alter cytoplasmic calcium levels revealed that ATP release is a calcium-dependent process and may occur through vesicular fusion, an important step in the polar growth of actively growing root hairs. Reactive oxygen species (ROS) activity at the root hair tip is not only essential for root hair growth, but also dependent on the cytoplasmic calcium levels. Whereas application of exogenous ATP and a chitin mixture increased ROS activity in root hairs, no changes were observed in response to adenosine, AMP, ADP, and nonhydrolyzable ATP (betagammameATP). However, application of exogenous potato (Solanum tuberosum) apyrase (ATPase) decreased ROS activity, suggesting that cytoplasmic calcium gradients and ROS activity are closely associated with eATP release. PMID:16963521

Kim, Sung-Yong; Sivaguru, Mayandi; Stacey, Gary

2006-09-08

48

Survey of ATP Applicants 2002: Portfolio of Survey Factsheets.  

National Technical Information Service (NTIS)

Contents: Applicant Satisfaction with ATP Staff; Time and Cost for ATP Proposal Preparation; ATP Proposal Debriefing: Nonawardee Views; Applicant Perceptions of the ATP Proposal Process; Applicant Views of the ATP Proposal Preparation Kit and Electronic S...

2005-01-01

49

75 FR 25294 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-High Definition...  

Federal Register 2010, 2011, 2012, 2013

...Definition Metrology and Process-2 Micron Manufacturing Under ATP Award No. 70NANB77041 Notice is hereby given that, on March...Definition Metrology and Process-2 Micron Manufacturing under ATP Award No. 70NANB7H7041 has filed written notifications...

2010-05-07

50

A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia  

PubMed Central

Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and ?,?-methylene ATP (?,?-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T2-T5) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25–4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 A?, 37 C fibers). Epicardial application of ATP (1–4 ?mol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 ?mol), ADP (2 ?mol), a P2Y agonist, and ?,?-meATP (0.5 ?mol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2?,4?-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 ?mol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2–4 ?mol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory neurites.

Longhurst, John C.

2010-01-01

51

A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.  

PubMed

Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and ?,?-methylene ATP (?,?-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 A?, 37 C fibers). Epicardial application of ATP (1-4 ?mol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 ?mol), ADP (2 ?mol), a P2Y agonist, and ?,?-meATP (0.5 ?mol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 ?mol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 ?mol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory neurites. PMID:20870803

Fu, Liang-Wu; Longhurst, John C

2010-09-24

52

43 CFR 10000.3 - Definitions.  

Code of Federal Regulations, 2012 CFR

...Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND CONSERVATION COMMISSION ORGANIZATION...FUNCTIONS § 10000.3 Definitions. Act refers to the Central Utah Project Completion Act, Titles II, III, IV, V, and VI of...

2012-10-01

53

ATP dependence of H+ secretion.  

PubMed

Cells in isolated rabbit gastric gland were made permeable to ATP by high voltage discharge across a gland suspension. In both normal (5.4 mM K+) and high K+ (108 mM) medium, this electrical shock resulted in a marked reduction in the ability of the parietal cell to produce and accumulate acid. Acid production was monitored both microscopically by acridine orange accumulation in the secretory canaliculus and by accumulation of the weak base [14C]aminopyrine. In 108 mM K+ solutions but not in 5.4 mM K+ solutions 5, mM ATP was able to restore the accumulation of these probes to control (unshocked) levels. When shocked glands had been previously stimulated by secretagogues, the aminopyrine accumulation ratio was only partly restored by ATP. Inhibition of mitochondrial respiration by cyanide, azide, or Amytal abolished acid secretion; the subsequent addition of ATP to shocked glands increased the aminopyrine accumulation ratio to 47 and resulted in an acridine orange fluorescence indistinguishable from that of histamine-stimulated, unshocked glands. We conclude that ATP can act as a substrate for H+ secretion in the parietal cell, and that perhaps no additional energy source is necessary. PMID:7372713

Berglindh, T; Dibona, D R; Pace, C S; Sachs, G

1980-05-01

54

ATP synthase in slow- and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction.  

PubMed

ATP synthase is a validated drug target for the treatment of tuberculosis, and ATP synthase inhibitors are promising candidate drugs for the treatment of infections caused by other slow-growing mycobacteria, such as Mycobacterium leprae and Mycobacterium ulcerans. ATP synthase is an essential enzyme in the energy metabolism of Mycobacterium tuberculosis; however, no biochemical data are available to characterize the role of ATP synthase in slow-growing mycobacterial strains. Here, we show that inverted membrane vesicles from the slow-growing model strain Mycobacterium bovis BCG are active in ATP synthesis, but ATP synthase displays no detectable ATP hydrolysis activity and does not set up a proton-motive force (PMF) using ATP as a substrate. Treatment with methanol as well as PMF activation unmasked the ATP hydrolysis activity, indicating that the intrinsic subunit ? and inhibitory ADP are responsible for the suppression of hydrolytic activity. These results suggest that the enzyme is needed for the synthesis of ATP, not for the maintenance of the PMF. For the development of new antimycobacterial drugs acting on ATP synthase, screening for ATP synthesis inhibitors, but not for ATP hydrolysis blockers, can be regarded as a promising strategy. PMID:21039782

Haagsma, Anna C; Driessen, Nicole N; Hahn, Marc-Manuel; Lill, Holger; Bald, Dirk

2010-10-07

55

'Domino' systems biology and the 'A' of ATP.  

PubMed

We develop a strategic 'domino' approach that starts with one key feature of cell function and the main process providing for it, and then adds additional processes and components only as necessary to explain provoked experimental observations. The approach is here applied to the energy metabolism of yeast in a glucose limited chemostat, subjected to a sudden increase in glucose. The puzzles addressed include (i) the lack of increase in adenosine triphosphate (ATP) upon glucose addition, (ii) the lack of increase in adenosine diphosphate (ADP) when ATP is hydrolyzed, and (iii) the rapid disappearance of the 'A' (adenine) moiety of ATP. Neither the incorporation of nucleotides into new biomass, nor steady de novo synthesis of adenosine monophosphate (AMP) explains. Cycling of the 'A' moiety accelerates when the cell's energy state is endangered, another essential domino among the seven required for understanding of the experimental observations. This new domino analysis shows how strategic experimental design and observations in tandem with theory and modeling may identify and resolve important paradoxes. It also highlights the hitherto unexpected role of the 'A' component of ATP. PMID:23031542

Verma, Malkhey; Zakhartsev, Maksim; Reuss, Matthias; Westerhoff, Hans V

2012-09-29

56

Actin Polymerization and ATP Hydrolysis  

NASA Astrophysics Data System (ADS)

F-actin is the major component of muscle thin filaments and, more generally, of the microfilaments of the dynamic, multifunctional cytoskeletal systems of nonmuscle eukaryotic cells. Polymeric F-actin is formed by reversible noncovalent self-association of monomeric G-actin. To understand the dynamics of microfilament systems in cells, the dynamics of polymerization of pure actin must be understood. The following model has emerged from recent work. During the polymerization process, adenosine 5'-triphosphate (ATP) that is bound to G-actin is hydrolyzed to adenosine 5'-diphosphate (ADP) that is bound to F-actin. The hydrolysis reaction occurs on the F-actin subsequent to the polymerization reaction in two steps: cleavage of ATP followed by the slower release of inorganic phosphate (Pi). As a result, at high rates of filament growth a transient cap of ATP-actin subunits exists at the ends of elongating filaments, and at steady state a stabilizing cap of ADP \\cdot Pi-actin subunits exists at the barbed ends of filaments. Cleavage of ATP results in a highly stable filament with bound ADP \\cdot Pi, and release of Pi destabilizes the filament. Thus these two steps of the hydrolytic reaction provide potential mechanisms for regulating the monomer-polymer transition.

Korn, Edward D.; Carlier, Marie-France; Pantaloni, Dominique

1987-10-01

57

Anthraniloyl ATP, a fluorescent analog of ATP, as a substrate for dynein ATPase and flagellar motility.  

PubMed

We synthesized an anthraniloyl ATP (ant-ATP), which has a fluorescent anthraniloyl moiety at the OH group of ribose, to elucidate the mechanism of flagellar bend formation and its propagation in relation to the mechanochemical cycle of dynein ATPase. This fluorescent analog of ATP was efficiently hydrolyzed by 21 S dynein from sea urchin sperm flagella with Km = 7.6 microM, whereas the Km was 12 microM when ATP was used as the substrate. Similar Vmax values were obtained with both ATP and ant-ATP. Inhibition of the hydrolysis of ant-ATP by vanadate was a little smaller than that with ATP. Photosensitized cleavage of 21 S dynein heavy chains in the presence of ant-ATP and vanadate was also a little less efficient than that in the presence of ATP and vanadate. Ant-ATP also induced the disintegration of the trypsin-treated axoneme and the motility of demembranated sperm in a manner similar to ATP. When ATP was used as a substrate for the demembranated sperm, the apparent Michaelis constant for beat frequency (Km f) was 0.22 mM and the maximum frequency (fmax) was 36 Hz, whereas Km f) was 0.14 mM and fmax was 20 Hz for ant-ATP. Thus ant-ATP could be an efficient fluorescent analog of ATP for studying dynein ATPase and the mechanisms of flagellar motility. PMID:2528327

Inaba, K; Okuno, M; Mohri, H

1989-10-01

58

Caveola ATP synthase mediates ATP release in vascular endothelial cells exposed to shear stress  

Microsoft Academic Search

Endothelial cells (ECs) release ATP in response to shear stress, a mechanical force generated by blood flow, and the ATP released modulates EC functions through activation of purinoceptors. The molecular mechanism of the shear-stress-induced ATP release, however, has not been fully understood. In this study, we have demonstrated that cell-surface ATP synthase is involved in shear stress-induced ATP release. Immunofluorescence

K. Yamamoto; S. Obi; N. Shimizu; S. Kumagaya; J. Ando

2007-01-01

59

Initiation of Purinergic Signaling by Exocytosis of ATP-containing Vesicles in Liver Epithelium*  

PubMed Central

Extracellular ATP represents an important autocrine/paracrine signaling molecule within the liver. The mechanisms responsible for ATP release are unknown, and alternative pathways have been proposed, including either conductive ATP movement through channels or exocytosis of ATP-enriched vesicles, although direct evidence from liver cells has been lacking. Utilizing dynamic imaging modalities (confocal and total internal reflection fluorescence microscopy and luminescence detection utilizing a high sensitivity CCD camera) at different scales, including confluent cell populations, single cells, and the intracellular submembrane space, we have demonstrated in a model liver cell line that (i) ATP release is not uniform but reflects point source release by a defined subset of cells; (ii) ATP within cells is localized to discrete zones of high intensity that are ?1 ?m in diameter, suggesting a vesicular localization; (iii) these vesicles originate from a bafilomycin A1-sensitive pool, are depleted by hypotonic exposure, and are not rapidly replenished from recycling of endocytic vesicles; and (iv) exocytosis of vesicles in response to cell volume changes depends upon a complex series of signaling events that requires intact microtubules as well as phosphoinositide 3-kinase and protein kinase C. Collectively, these findings are most consistent with an essential role for exocytosis in regulated release of ATP and initiation of purinergic signaling in liver cells.

Feranchak, Andrew P.; Lewis, Matthew A.; Kresge, Charles; Sathe, Meghana; Bugde, Abhijit; Luby-Phelps, Kate; Antich, Peter P.; Fitz, J. Gregory

2010-01-01

60

ORIGINAL RESEARCH—EJACULATORY DISORDERS Changing Paradigms from a Historical DSM-III and DSM-IV View Toward an Evidence-Based Definition of Premature Ejaculation. Part I—Validity of DSM-IV-TR  

Microsoft Academic Search

Background. In former days, information obtained from randomized well-controlled clinical trials and epidemio- logical studies on premature ejaculation (PE) was not available, thereby hampering the efforts of the consecutive DSM Work Groups on Sexual Disorders to formulate an evidence-based definition of PE. The current DSM-IV- TR definition of PE is still nonevidence based. In addition, the requirement that persistent self-perceived

Marcel D. Waldinger; Dave H. Schweitzer

61

Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part II--proposals for DSM-V and ICD11  

Microsoft Academic Search

In the Diagnostic and Statistical Manual of Mental Disorders (DSM), a descriptive definition for\\u000apremature ejaculation (PE) that was based on historical assumptions has been accepted.\\u000aAim. To formulate a new functional definition of PE in the DSM.\\u000aMethods. A “syndrome” approach instead of a “complaint” approach is applied and evidence-based data from\\u000aepidemiological and clinical studies are used.\\u000aResults.

Marcel D. Waldinger; Dave H. Schweitzer

2006-01-01

62

Rho-family GTPases modulate Ca(2+) -dependent ATP release from astrocytes.  

PubMed

Previously, we reported that activation of G protein-coupled receptors (GPCR) in 1321N1 human astrocytoma cells elicits a rapid release of ATP that is partially dependent on a G(q)/phophospholipase C (PLC)/Ca(2+) mobilization signaling cascade. In this study we assessed the role of Rho-family GTPase signaling as an additional pathway for the regulation of ATP release in response to activation of protease-activated receptor-1 (PAR1), lysophosphatidic acid receptor (LPAR), and M3-muscarinic (M3R) GPCRs. Thrombin (or other PAR1 peptide agonists), LPA, and carbachol triggered quantitatively similar Ca(2+) mobilization responses, but only thrombin and LPA caused rapid accumulation of active GTP-bound Rho. The ability to elicit Rho activation correlated with the markedly higher efficacy of thrombin and LPA, relative to carbachol, as ATP secretagogues. Clostridium difficile toxin B and Clostridium botulinum C3 exoenzyme, which inhibit Rho-GTPases, attenuated the thrombin- and LPA-stimulated ATP release but did not decrease carbachol-stimulated release. Thus the ability of certain G(q)-coupled receptors to additionally stimulate Rho-GTPases acts to strongly potentiate a Ca(2+)-activated ATP release pathway. However, pharmacological inhibition of Rho kinase I/II or myosin light chain kinase did not attenuate ATP release. PAR1-induced ATP release was also reduced twofold by brefeldin treatment suggesting the possible mobilization of Golgi-derived, ATP-containing secretory vesicles. ATP release was also markedly repressed by the gap junction channel inhibitor carbenoxolone in the absence of any obvious thrombin-induced change in membrane permeability indicative of hemichannel gating. PMID:18495810

Blum, Andrew E; Joseph, Sheldon M; Przybylski, Ronald J; Dubyak, George R

2008-05-21

63

Rho-family GTPases modulate Ca2+-dependent ATP release from astrocytes  

PubMed Central

Previously, we reported that activation of G protein-coupled receptors (GPCR) in 1321N1 human astrocytoma cells elicits a rapid release of ATP that is partially dependent on a Gq/phophospholipase C (PLC)/Ca2+ mobilization signaling cascade. In this study we assessed the role of Rho-family GTPase signaling as an additional pathway for the regulation of ATP release in response to activation of protease-activated receptor-1 (PAR1), lysophosphatidic acid receptor (LPAR), and M3-muscarinic (M3R) GPCRs. Thrombin (or other PAR1 peptide agonists), LPA, and carbachol triggered quantitatively similar Ca2+ mobilization responses, but only thrombin and LPA caused rapid accumulation of active GTP-bound Rho. The ability to elicit Rho activation correlated with the markedly higher efficacy of thrombin and LPA, relative to carbachol, as ATP secretagogues. Clostridium difficile toxin B and Clostridium botulinum C3 exoenzyme, which inhibit Rho-GTPases, attenuated the thrombin- and LPA-stimulated ATP release but did not decrease carbachol-stimulated release. Thus the ability of certain Gq-coupled receptors to additionally stimulate Rho-GTPases acts to strongly potentiate a Ca2+-activated ATP release pathway. However, pharmacological inhibition of Rho kinase I/II or myosin light chain kinase did not attenuate ATP release. PAR1-induced ATP release was also reduced twofold by brefeldin treatment suggesting the possible mobilization of Golgi-derived, ATP-containing secretory vesicles. ATP release was also markedly repressed by the gap junction channel inhibitor carbenoxolone in the absence of any obvious thrombin-induced change in membrane permeability indicative of hemichannel gating.

Blum, Andrew E.; Joseph, Sheldon M.; Przybylski, Ronald J.; Dubyak, George R.

2008-01-01

64

ATP interaction with the open state of the K(ATP) channel.  

PubMed Central

The mechanism of ATP-sensitive potassium (K(ATP)) channel closure by ATP is unclear, and various kinetic models in which ATP binds to open or to closed states have previously been presented. Effects of phosphatidylinositol bisphosphate (PIP2) and multiple Kir6.2 mutations on ATP inhibition and open probability in the absence of ATP are explainable in kinetic models where ATP stabilizes a closed state and interaction with an open state is not required. Evidence that ATP can in fact interact with the open state of the channel is presented here. The mutant Kir6.2[L164C] is very sensitive to Cd2+ block, but very insensitive to ATP, with no significant inhibition in 1 mM ATP. However, 1 mM ATP fully protects the channel from Cd2+ block. Allosteric kinetic models in which the channel can be in either open or closed states with or without ATP bound are considered. Such models predict a pedestal in the ATP inhibition, i.e., a maximal amount of inhibition at saturating ATP concentrations. This pedestal is predicted to occur at >50 mM ATP in the L164C mutant, but at >1 mM in the double mutant L164C/R176A. As predicted, ATP inhibits Kir6.2[L164C/R176A] to a maximum of approximately 40%, with a clear plateau beyond 2 mM. These results indicate that ATP acts as an allosteric ligand, interacting with both open and closed states of the channel.

Enkvetchakul, D; Loussouarn, G; Makhina, E; Nichols, C G

2001-01-01

65

Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium  

PubMed Central

Background ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s) by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices. Results Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, ??MeATP and Bz-ATP) and a G protein-coupled P2Y receptor agonist (UTP). Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone. Conclusions The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP release following injury could lead to progenitor cell proliferation, differentiation and regeneration. Thus, understanding mechanisms of ATP release is of paramount importance to improve our knowledge about tissue homeostasis and post-injury neuroregeneration. It will lead to development of treatments to restore loss of smell and, when transposed to the central nervous system, improve recovery following central nervous system injury.

2012-01-01

66

Stability of ATP in Antarctic mineral soils  

Microsoft Academic Search

The stability of exogenous ATP in Antarctic Ross desert soils has been assessed using bioluminescence monitoring of ATP-supplemented\\u000a samples. Under typical east Antarctic dry valley summer conditions (?3 to +15°C), exogenous ATP was degraded with a half-life\\u000a of between 0.5 and 30 h. The rate of degradation was affected, in order of significance, by soil biomass levels, temperature\\u000a and water content.

Don A. Cowan; Ana Casanueva

2007-01-01

67

ATP synthase: motoring to the finish line.  

PubMed

Protonmotive force produced by the electron transport chain is harnessed by the rotary molecular nanomotor ATP synthase to generate ATP. In this issue of Cell, Adachi et al. (2007), in a dazzling display of technical sophistication, now disentangle the coupling between the mechanical force generated by rotation of the ATP synthase subunits and the chemical reactions that occur simultaneously at the enzyme's three catalytic sites. PMID:17662937

Senior, Alan E

2007-07-27

68

EP2 receptors mediate airway relaxation to substance P, ATP, and PGE2.  

PubMed

Substance P (SP) and ATP evoke transient, epithelium-dependent relaxation of constricted mouse tracheal smooth muscle. Relaxation to either SP or ATP is blocked by indomethacin, but the specific eicosanoid(s) involved have not been definitively identified. SP and ATP are reported to release PGE2 from airway epithelium in other species, suggesting PGE2 as a likely mediator in epithelium-dependent airway relaxation. Using mice homozygous for a gene-targeted deletion of the EP2 receptor [EP2(-/-)], one of the PGE2 receptors, we tested the hypothesis that PGE2 is the primary mediator of relaxation to SP or ATP. Relaxation in response to SP or ATP was significantly reduced in tracheas from EP2(-/-) mice. There were no differences between EP2(-/-) and wild-type tracheas in their physical dimensions, contraction to ACh, or relaxation to isoproterenol, thus ruling out any general alterations of smooth muscle function. There were also no differences between EP2(-/-) and wild-type tracheas in basal or stimulated PGE2 production. Exogenous PGE2 produced significantly less relaxation in EP2(-/-) tracheas compared with the wild type. Taken together, this experimental evidence supports the following two conclusions: EP2 receptors are of primary importance in airway relaxation to PGE2 and relaxation to SP or ATP is mediated through PGE2 acting on EP2 receptors. PMID:11435222

Fortner, C N; Breyer, R M; Paul, R J

2001-08-01

69

How ATP Inhibits the Open KATP Channel  

PubMed Central

ATP-sensitive potassium (KATP) channels are composed of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits. Binding of ATP to Kir6.2 leads to inhibition of channel activity. Because there are four subunits and thus four ATP-binding sites, four binding events are possible. ATP binds to both the open and closed states of the channel and produces a decrease in the mean open time, a reduction in the mean burst duration, and an increase in the frequency and duration of the interburst closed states. Here, we investigate the mechanism of interaction of ATP with the open state of the channel by analyzing the single-channel kinetics of concatenated Kir6.2 tetramers containing from zero to four mutated Kir6.2 subunits that possess an impaired ATP-binding site. We show that the ATP-dependent decrease in the mean burst duration is well described by a Monod-Wyman-Changeux model in which channel closing is produced by all four subunits acting in a single concerted step. The data are inconsistent with a Hodgkin-Huxley model (four independent steps) or a dimer model (two independent dimers). When the channel is open, ATP binds to a single ATP-binding site with a dissociation constant of 300 ?M.

Craig, Tim J.; Ashcroft, Frances M.; Proks, Peter

2008-01-01

70

Conformational dynamics of ATP/Mg:ATP in motor proteins via data mining and molecular simulation  

NASA Astrophysics Data System (ADS)

The conformational diversity of ATP/Mg:ATP in motor proteins was investigated using molecular dynamics and data mining. Adenosine triphosphate (ATP) conformations were found to be constrained mostly by inter cavity motifs in the motor proteins. It is demonstrated that ATP favors extended conformations in the tight pockets of motor proteins such as F1-ATPase and actin whereas compact structures are favored in motor proteins such as RNA polymerase and DNA helicase. The incorporation of Mg2+ leads to increased flexibility of ATP molecules. The differences in the conformational dynamics of ATP/Mg:ATP in various motor proteins was quantified by the radius of gyration. The relationship between the simulation results and those obtained by data mining of motor proteins available in the protein data bank is analyzed. The data mining analysis of motor proteins supports the conformational diversity of the phosphate group of ATP obtained computationally.

Bojovschi, A.; Liu, Ming S.; Sadus, Richard J.

2012-08-01

71

Expression in Mouse Kidney of Membrane Copper Transporters Atp7a and Atp7b  

Microsoft Academic Search

Copper is essential for activity of many enzymes, but is toxic in excess. Several copper proteins are required for copper homeostasis. ATP7A and ATP7B are genes encoding membrane copper transporters. ATP7A, defective in Menkes disease (MNK), is expressed in many tissues involved primarily in copper uptake from dietary sources. ATP7B, defective in Wilson disease (WND), is essential for copper excretion.

Steven D. P. Moore; Diane W. Cox

2002-01-01

72

Antithrombin III, Human (Thrombate III)  

Center for Biologics Evaluation and Research (CBER)

... are significant safety risks involved with the use of Thrombate III for hemostasis, particularly involving the interaction of Thrombate III and heparin. ... More results from www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/complianceactivities

73

Light-driven production of ATP catalysed by F0F1-ATP synthase in an artificial photosynthetic membrane  

NASA Astrophysics Data System (ADS)

Energy-transducing membranes of living organisms couple spontaneous to non-spontaneous processes through the intermediacy of protonmotive force (p.m.f.) - an imbalance in electrochemical potential of protons across the membrane. In most organisms, p.m.f. is generated by redox reactions that are either photochemically driven, such as those in photosynthetic reaction centres, or intrinsically spontaneous, such as those of oxidative phosphorylation in mitochondria. Transmembrane proteins (such as the cytochromes and complexes I, III and IV in the electron-transport chain in the inner mitochondrial membrane) couple the redox reactions to proton translocation, thereby conserving a fraction of the redox chemical potential as p.m.f. Many transducer proteins couple p.m.f. to the performance of biochemical work, such as biochemical synthesis and mechanical and transport processes. Recently, an artificial photosynthetic membrane was reported in which a photocyclic process was used to transport protons across a liposomal membrane, resulting in acidification of the liposome's internal volume. If significant p.m.f. is generated in this system, then incorporating an appropriate transducer into the liposomal bilayer should make it possible to drive a non-spontaneous chemical process. Here we report the incorporation of FOF1-ATP synthase into liposomes containing the components of the proton-pumping photocycle. Irradiation of this artificial membrane with visible light results in the uncoupler- and inhibitor-sensitive synthesis of adenosine triphosphate (ATP) against an ATP chemical potential of ~12kcalmol-1, with a quantum yield of more than 7%. This system mimics the process by which photosynthetic bacteria convert light energy into ATP chemical potential.

Steinberg-Yfrach, Gali; Rigaud, Jean-Louis; Durantini, Edgardo N.; Moore, Ana L.; Gust, Devens; Moore, Thomas A.

1998-04-01

74

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).  

National Technical Information Service (NTIS)

The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) presents the National Cholesterol Education Program's (NCEP's) updated recommendations for cholesterol...

2002-01-01

75

ATP2B4/A0114  

NSDL National Science Digital Library

Plasma membrane calcium-transporting ATPase 4 (ATP2B4), also known as A0114, is a multi-pass membrane protein, which catalyzes the hydrolysis of adenosine triphosphate (ATP) coupled with the transport of calcium out of the cell.

2009-04-14

76

A unified, long-term, high-latitude stratospheric aerosol and cloud database using SAM II, SAGE II, and POAM II\\/III data: Algorithm description, database definition, and climatology  

Microsoft Academic Search

A 22 year, high-latitude, stratospheric aerosol and cloud database has been formed in a “unified” manner by combining the Stratospheric Aerosol Measurement (SAM) II, Stratospheric Aerosol and Gas Measurement (SAGE) II, Polar Ozone and Aerosol Measurement (POAM) II, and POAM III 1 ?m aerosol extinction profiles. The database is “unified” in that it embodies similar aerosol extinction measurements, uses a

Michael Fromm; Jerome Alfred; Michael Pitts

2003-01-01

77

A unified, long-term, high-latitude stratospheric aerosol and cloud database using SAM II, SAGE II, and POAM II\\/III data: Algorithm description, database definition, and climatology  

Microsoft Academic Search

A 22 year, high-latitude, stratospheric aerosol and cloud database has been formed in a ``unified'' manner by combining the Stratospheric Aerosol Measurement (SAM) II, Stratospheric Aerosol and Gas Measurement (SAGE) II, Polar Ozone and Aerosol Measurement (POAM) II, and POAM III 1 mum aerosol extinction profiles. The database is ``unified'' in that it embodies similar aerosol extinction measurements, uses a

Michael Fromm; Jerome Alfred; Michael Pitts

2003-01-01

78

Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part I--validity of DSM-IV-TR  

Microsoft Academic Search

In former days, information obtained from randomized well-controlled clinical trials and epidemiological\\u000astudies on premature ejaculation (PE) was not available, thereby hampering the efforts of the consecutive\\u000aDSM Work Groups on Sexual Disorders to formulate an evidence-based definition of PE. The current DSM-IVTR\\u000adefinition of PE is still nonevidence based. In addition, the requirement that persistent self-perceived PE,\\u000adistress, and

Marcel D. Waldinger; Dave H. Schweitzer

2006-01-01

79

Structural organization of mitochondrial ATP synthase.  

PubMed

Specific modules and subcomplexes like F(1) and F(0)-parts, F(1)-c subcomplexes, peripheral and central stalks, and the rotor part comprising a ring of c-subunits with attached subunits gamma, delta, and epsilon can be identified in yeast and mammalian ATP synthase. Four subunits, alpha(3)beta(3), OSCP, and h, seem to form a structural entity at the extramembranous rotor/stator interface (gamma/alpha(3)beta(3)) to hold and stabilize the rotor in the holo-enzyme. The intramembranous rotor/stator interface (c-ring/a-subunit) must be dynamic to guarantee unhindered rotation. Unexpectedly, a c(10)a-assembly could be isolated with almost quantitive yield suggesting that an intermediate step in the rotating mechanism was frozen under the conditions used. Isolation of dimeric a-subunit and (c(10))(2)a(2)-complex from dimeric ATP synthase suggested that the a-subunit stabilizes the same monomer-monomer interface that had been shown to involve also subunits e, g, b, i, and h. The natural inhibitor protein Inh1 does not favor oligomerization of yeast ATP synthase. Other candidates for the oligomerization of dimeric ATP synthase building blocks are discussed, e.g. the transporters for inorganic phosphate and ADP/ATP that had been identified as constituents of ATP synthasomes. Independent approaches are presented that support previous reports on the existence of ATP synthasomes in the mitochondrial membrane. PMID:18485888

Wittig, Ilka; Schägger, Hermann

2008-04-27

80

ATP Photosynthetic vesicles for light-driven bioprocesses  

Microsoft Academic Search

We prepared ATP photosynthetic vesicles from inside-out membranes of Escherichia coli cells that express delta-rhodopsin (a novel light-driven H+ transporter) and TF0F1-ATP synthase (a thermo-stable ATP synthase). These vesicles showed light-dependent ATP synthesis. Furthermore, coupling the\\u000a ATP photosynthetic vesicles with an ATP-hydrolyzing hexokinase enabled light-dependent glucose consumption. The ATP photosynthetic\\u000a vesicles indicate their potential to applied to light-driven ATP-regenerating bioprocess

Kiyotaka Y. Hara; Rie Suzuki; Toshiharu Suzuki; Masasuke Yoshida; Kuniki Kino

2011-01-01

81

Inhibition of Ecto-ATPase by the P 2Purinoceptor Agonists, ATP?S, ?,?-Methylene-ATP, and AMP-PNP, in Endothelial Cells  

Microsoft Academic Search

Ecto-ATPase is a plasma membrane-bound enzyme that sequentially dephosphorylates extracellular nucleotides such as ATP. This breakdown of ATP and other nucleotides makes it difficult to characterize and classify P2purinoceptors. We have previously shown that the P2purinergic antagonists, PPADS, suramin and reactive blue, act as ecto-ATPase inhibitors in various cell lines. Here, we show that the P2purinergic agonists, ATP?S, ?,?-methylene ATP

Bing Chang Chen; Wan-Wan Lin

1997-01-01

82

Target-induced structure switching of hairpin aptamers for label-free and sensitive fluorescent detection of ATP via exonuclease-catalyzed target recycling amplification.  

PubMed

In this work, we described the development of a new label-free, simple and sensitive fluorescent ATP sensing platform based on exonuclease III (Exo III)-catalyzed target recycling (ECTR) amplification and SYBR Green I indicator. The hairpin aptamer probes underwent conformational structure switching and re-configuration in the presence of ATP, which led to catalytic cleavage of the re-configured aptamers by Exo III to release ATP and to initiate the ECTR process. Such ECTR process resulted in the digestion of a significant number of the hairpin aptamer probes, leading to much less intercalation of SYBR Green I to the hairpin stems and drastic suppression of the fluorescence emission for sensitive ATP detection down to the low nanomolar level. Due to the highly specific affinity bindings between aptamers and ATP, the developed method exhibited excellent selectivity toward ATP against other analogous molecules. Besides, our ATP sensing approach used un-modified aptamer probes and could be performed in a "mix-and-detect" fashion in homogenous solutions. All these distinct advantages of the developed method thus made it hold great potential for the development of simple and robust sensing strategies for the detection of other small molecules. PMID:23974161

Xu, Yunying; Xu, Jin; Xiang, Yun; Yuan, Ruo; Chai, Yaqin

2013-08-09

83

29 CFR 825.800 - Definitions.  

Code of Federal Regulations, 2010 CFR

... (iii) Christian Science Practitioners listed...treatment from a Christian Science practitioner, an employee...other than a Christian Science practitioner except...employee: See the definition of Teacher in this...or leave taken several days at a time spread...

2010-07-01

84

29 CFR 825.800 - Definitions.  

Code of Federal Regulations, 2010 CFR

... (iii) Christian Science Practitioners listed...treatment from a Christian Science practitioner, an employee...other than a Christian Science practitioner except...employee: See the definition of Teacher in this...or leave taken several days at a time spread...

2009-07-01

85

ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase.  

PubMed

Human ATP-citrate lyase (EC 2.3.3.8) is the cytoplasmic enzyme that catalyzes the production of acetyl-CoA from citrate, CoA and ATP. The amino-terminal portion of the enzyme, containing residues 1-817, was crystallized in the presence of tartrate, ATP and magnesium ions. The crystals diffracted to 2.3 Å resolution. The structure shows ADP-Mg(2+) bound to the domain that possesses the ATP-grasp fold. The structure demonstrates that this crystal form could be used to investigate the structures of complexes with inhibitors of ATP-citrate lyase that bind at either the citrate- or ATP-binding site. PMID:22102020

Sun, Tianjun; Hayakawa, Koto; Fraser, Marie E

2011-09-24

86

ATP determination with the Tricarb scintillation counter  

Microsoft Academic Search

Zusammenfassung Die Arbeit beschreibt eine neue Technik zur Bestimmung geringster Mengen von ATP (10–11 Mol und weniger) mit der Luciferin-Luciferase-Methode. Die dabei erzeugten Impulse werden mit einem Scintillationszähler gemessen.

E. Tal; S. Dikstein; F. G. Sulman

1964-01-01

87

Alternative proton binding mode in ATP synthases.  

PubMed

ATP synthases are rotary engines which use the energy stored in a transmembrane electrochemical gradient of protons or sodium ions to catalyze the formation of ATP by ADP and inorganic phosphate. Current models predict that protonation/deprotonation of specific amino acids of the rotating c-ring, extracting protons from one side and delivering them to the other side of the membrane, are at the core of the proton translocation mechanism of these enzymes. In this minireview, an alternative proton binding mechanism is presented, considering hydronium ion coordination as proposed earlier. Biochemical data and structural considerations provide evidence for two different proton binding modes in the c-ring of H+-translocating ATP synthases. Recent investigations in several other proton translocating membrane proteins suggest, that hydronium ion coordination by proteins might display a general principle which was so far underestimated in ATP synthases. PMID:17965925

von Ballmoos, Christoph

2007-12-01

88

ATP1A1/A0340  

NSDL National Science Digital Library

Sodium/potassium-transporting ATPase alpha-1 subunit (ATP1A1, also known as A0340) is an isoform of the catalytic subunit of the three subunit cation transporting pump, sodium/potassium-transporting ATPase.

2009-04-14

89

Reinterpreting the action of ATP analogs on K(ATP) channels.  

PubMed

Neuroendocrine-type K(ATP) channels, (SUR1/Kir6.2)4, couple the transmembrane flux of K(+), and thus membrane potential, with cellular metabolism in various cell types including insulin-secreting ?-cells. Mutant channels with reduced activity are a cause of congenital hyperinsulinism, whereas hyperactive channels are a cause of neonatal diabetes. A current regulatory model proposes that ATP hydrolysis is required to switch SUR1 into post-hydrolytic conformations able to antagonize the inhibitory action of nucleotide binding at the Kir6.2 pore, thus coupling enzymatic and channel activities. Alterations in SUR1 ATPase activity are proposed to contribute to neonatal diabetes and type 2 diabetes risk. The regulatory model is partly based on the reduced ability of ATP analogs such as adenosine 5'-(?,?-imino)triphosphate (AMP-PNP) and adenosine 5'-O-(thiotriphosphate) (ATP?S) to stimulate channel activity, presumably by reducing hydrolysis. This study uses a substitution at the catalytic glutamate, SUR(1E1507Q), with a significantly increased affinity for ATP, to probe the action of these ATP analogs on conformational switching. ATP?S, a slowly hydrolyzable analog, switches SUR1 conformations, albeit with reduced affinity. Nonhydrolyzable AMP-PNP and adenosine 5'-(?,?-methylenetriphosphate) (AMP-PCP) alone fail to switch SUR1, but do reverse ATP-induced switching. AMP-PCP displaces 8-azido-[(32)P]ATP from the noncanonical NBD1 of SUR1. This is consistent with structural data on an asymmetric bacterial ABC protein that shows that AMP-PNP binds selectively to the noncanonical NBD to prevent conformational switching. The results imply that MgAMP-PNP and MgAMP-PCP (AMP-PxP) fail to activate K(ATP) channels because they do not support NBD dimerization and conformational switching, rather than by limiting enzymatic activity. PMID:23665564

Ortiz, David; Gossack, Lindsay; Quast, Ulrich; Bryan, Joseph

2013-05-12

90

Biological availability of aluminum in commercial ATP  

Microsoft Academic Search

Aluminum is a contaminant of commercial ATP. We have used the fluorescent chelation agent morin to define the conditions of solution pH and incubation period under which this contaminating aluminum was biologically available. The biological significance of our model ligand morin was tested in media in which the morin was replaced with the A?P(25–35) peptide. Aluminum-contaminated ATP was shown to

Christopher Exley; J. Derek Birchall

1996-01-01

91

Mitochondrial ATP synthase: architecture, function and pathology  

Microsoft Academic Search

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to\\u000a phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and

An I. Jonckheere; Jan A. M. Smeitink; Richard J. T. Rodenburg

92

ATP citrate lyase in cholinergic nerve endings  

Microsoft Academic Search

The activity of ATP-citrate lyase in homogenates of five selected rat brain regions varied from 2.93 to 6.90 nmol\\/min\\/mg of protein in the following order: cerebellum 3), synaptosomal (B) and synaptoplasmic (Bs) fractions from the different regions (r=0.92–0.99). These data indicate that activity of ATP-citrate lyase in cholinergic neurons is several times higher than that present in glial and noncholinergic

A. Szutowicz; M. Stcepie?; H. Bielarczyk; J. Kabata; W. Lysiak

1982-01-01

93

An ATP signalling pathway in plant cells: extracellular ATP triggers programmed cell death in Populus euphratica.  

PubMed

We elucidated the extracellular ATP (eATP) signalling cascade active in programmed cell death (PCD) using cell cultures of Populus euphratica. Millimolar amounts of eATP induced a dose- and time-dependent reduction in viability, and the agonist-treated cells displayed hallmark features of PCD. eATP caused an elevation of cytosolic Ca(2+) levels, resulting in Ca(2+) uptake by the mitochondria and subsequent H(2) O(2) accumulation. P.?euphratica exhibited an increased mitochondrial transmembrane potential, and cytochrome c was released without opening of the permeability transition pore over the period of ATP stimulation. Moreover, the eATP-induced increase of intracellular ATP, essential for the activation of caspase-like proteases and subsequent PCD, was found to be related to increased mitochondrial transmembrane potential. NO is implicated as a downstream component of the cytosolic Ca(2+) concentration but plays a negligible role in eATP-stimulated cell death. We speculate that ATP binds purinoceptors in the plasma membrane, leading to the induction of downstream intermediate signals, as the proposed sequence of events in PCD signalling was terminated by the animal P2 receptor antagonist suramin. PMID:22070751

Sun, Jian; Zhang, Chun-Lan; Deng, Shu-Rong; Lu, Cun-Fu; Shen, Xin; Zhou, Xiao-Yang; Zheng, Xiao-Jiang; Hu, Zan-Min; Chen, Shao-Liang

2011-12-06

94

Mussel and mammalian ATP synthase share the same bioenergetic cost of ATP.  

PubMed

The molecular mechanism by which the membrane-embedded FO sector of the mitochondrial ATP synthase translocates protons, thus dissipating the transmembrane protonmotive force and leading to ATP synthesis, involves the neutralization of the carboxylate residues of the c-ring. Carboxylates are thought to constitute the binding sites for ion translocation. In order to cast light on this mechanism, we exploited N,N'-dicyclohexylcarbodiimide, which covalently binds to FO c-ring carboxylates, and ionophores which selectively modulate the transmembrane electric (??) and chemical (?pH) gradients such as valinomycin, nigericin and dinitrophenol. ATP hydrolysis was evaluated in mitochondrial preparations and/or inside-out submitochondrial particles from mussel and mammalian tissues under different experimental conditions. The experiments pointed out striking similarities between mussel and mammalian mitochondrial ATP synthase. Our results support the hypothesis that the ATP synthase of Mytilus galloprovincialis induces intersubunit torque generation and translocates H(+) by coordinating the hydronium ion (H3O(+)) in the ion binding site of FO. Our results are consistent with the hypothesis that in mussel mitochondria the main component of the electrochemical gradient driving proton flux and ATP synthesis is ??. Therefore, mussel FO probably contains a small c-ring, which implies a low bioenergetic cost of making ATP as in mammals. These features which make mussel mitochondria as efficient in ATP production as mammalian ones may be especially advantageous in facultative aerobic species which intermittently exploit mitochondrial respiration to generate ATP. PMID:23456170

Nesci, Salvatore; Ventrella, Vittoria; Trombetti, Fabiana; Pirini, Maurizio; Pagliarani, Alessandra

2013-03-01

95

ATP synthase is necessary for microcin H47 antibiotic action.  

PubMed

Microcin H47 is a gene-encoded peptide antibiotic produced by a natural Escherichia coli strain isolated in Uruguay. In order to identify cellular components necessary for its antibiotic action, microcin H47-resistant mutants isolated in this work, as well as previously described mutants affected in membrane proteins, were analyzed. These studies indicated that (i) receptor outer membrane proteins for ferric-catechol siderophores would be involved in microcin-specific binding to the cell surface, (ii) the TonB pathway is needed for microcin H47 uptake, and (iii) the presence of the ATP synthase complex is necessary for microcin action. The possibility that this last structure contains the antibiotic target is discussed. PMID:11600367

Trujillo, M; Rodríguez, E; Laviña, M

2001-11-01

96

Storage and Release of ATP from Astrocytes in Culture  

Microsoft Academic Search

ATP is released from astrocytes and is involved in the propagation of calcium waves among them. Neuronal ATP secretion is quantal and calcium-dependent, but it has been suggested that ATP release from astrocytes may not be vesicular. Here we report that, besides the described basal ATP release facilitated by exposure to calcium-free medium, astrocytes release purine under conditions of elevated

Silvia Coco; Federico Calegari; Elena Pravettoni; Davide Pozzi; Elena Taverna; Patrizia Rosa; Michela Matteoli; Claudia Verderio

2003-01-01

97

Physiological levels of ATP negatively regulate proteasome function  

Microsoft Academic Search

Intracellular protein degradation by the ubiquitin-proteasome system is ATP dependent, and the optimal ATP concentration to activate proteasome function in vitro is ?100 ?M. Intracellular ATP levels are generally in the low millimolar range, but ATP at a level within this range was shown to inhibit proteasome peptidase activities in vitro. Here, we report new evidence that supports a hypothesis

Hongbiao Huang; Xiaoyan Zhang; Shujue Li; Ningning Liu; Wen Lian; Emily McDowell; Ping Zhou; Canguo Zhao; Haiping Guo; Change Zhang; Changshan Yang; Guangmei Wen; Xiaoxian Dong; Li Lu; Ningfang Ma; Weihua Dong; Q. Ping Dou; Xuejun Wang; Jinbao Liu

2010-01-01

98

Monitoring ATP release from individual cells with a biosensor  

Microsoft Academic Search

Adenosine triphosphate (ATP) is a neurotransmitter\\/neuromodulator in both central and peripheral nervous systems. Particularly\\u000a in the taste bud, a peripheral taste organ, ATP serves as an afferent neurotransmitter. To examine the mechanism that mediates\\u000a ATP secretion in taste cells, we elaborated an approach for monitoring ATP in an extracellular medium by employing a biosensor,\\u000a that is, cells responsive to ATP.

R. A. Romanov; A. A. Khokhlov; M. F. Bystrova; O. A. Rogachevskaja; Yu. E. Yatzenko; S. S. Kolesnikov

2007-01-01

99

C-Terminal mutations in the chloroplast ATP synthase gamma subunit impair ATP synthesis and stimulate ATP hydrolysis.  

PubMed

Two highly conserved amino acid residues, an arginine and a glutamine, located near the C-terminal end of the gamma subunit, form a "catch" by hydrogen bonding with residues in an anionic loop on one of the three catalytic beta subunits of the bovine mitochondrial F1-ATPase [Abrahams, J. P., Leslie, A. G., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628]. The catch is considered to play a critical role in the binding change mechanism whereby binding of ATP to one catalytic site releases the catch and induces a partial rotation of the gamma subunit. This role is supported by the observation that mutation of the equivalent arginine and glutamine residues in the Escherichia coli F1 gamma subunit drastically reduced all ATP-dependent catalytic activities of the enzyme [Greene, M. D., and Frasch, W. D. (2003) J. Biol. Chem. 278, 5194-5198]. In this study, we show that simultaneous substitution of the equivalent residues in the chloroplast F1 gamma subunit, arginine 304 and glutamine 305, with alanine decreased the level of proton-coupled ATP synthesis by more than 80%. Both the Mg2+-dependent and Ca2+-dependent ATP hydrolysis activities increased by more than 3-fold as a result of these mutations; however, the sulfite-stimulated activity decreased by more than 60%. The Mg2+-dependent, but not the Ca2+-dependent, ATPase activity of the double mutant was insensitive to inhibition by the phytotoxic inhibitor tentoxin, indicating selective loss of catalytic cooperativity in the presence of Mg2+ ions. The results indicate that the catch residues are required for efficient proton coupling and for activation of multisite catalysis when MgATP is the substrate. The catch is not, however, required for CaATP-driven multisite catalysis or, therefore, for rotation of the gamma subunit. PMID:18092810

He, Feng; Samra, Hardeep S; Johnson, Eric A; Degner, Nicholas R; McCarty, Richard E; Richter, Mark L

2007-12-20

100

ATP-driven stepwise rotation of FoF1-ATP synthase  

PubMed Central

FoF1-ATP synthase (FoF1) is a motor enzyme that couples ATP synthesis/hydrolysis with a transmembrane proton translocation. F1, a water-soluble ATPase portion of FoF1, rotates by repeating ATP-waiting dwell, 80° substep rotation, catalytic dwell, and 40°-substep rotation. Compared with F1, rotation of FoF1 has yet been poorly understood, and, here, we analyzed ATP-driven rotations of FoF1. Rotation was probed with an 80-nm bead attached to the ring of c subunits in the immobilized FoF1 and recorded with a submillisecond fast camera. The rotation rates at various ATP concentrations obeyed the curve defined by a Km of ?30 ?M and a Vmax of ?350 revolutions per second (at 37°C). At low ATP, ATP-waiting dwell was seen and the kon-ATP was estimated to be 3.6 × 107 M-1·s-1. At high ATP, fast, poorly defined stepwise motions were observed that probably reflect the catalytic dwells. When a slowly hydrolyzable substrate, adenosine 5?-[?-thio]triphosphate, was used, the catalytic dwells consisting of two events were seen more clearly at the angular position of ?80°. The rotational behavior of FoF1 resembles that of F1. This finding indicates that “friction” in Fo motor is negligible during the ATP-driven rotation. Tributyltin chloride, a specific inhibitor of proton translocation, slowed the rotation rate by 96%. However, dwells at clearly defined angular positions were not observed under these conditions, indicating that inhibition by tributyltin chloride is complex.

Ueno, Hiroshi; Suzuki, Toshiharu; Kinosita, Kazuhiko; Yoshida, Masasuke

2005-01-01

101

Torque Generation and Utilization in Motor Enzyme F0F1-ATP Synthase  

PubMed Central

ATP synthase (F0F1) is made of two motors, a proton-driven motor (F0) and an ATP-driven motor (F1), connected by a common rotary shaft, and catalyzes proton flow-driven ATP synthesis and ATP-driven proton pumping. In F1, the central ? subunit rotates inside the ?3?3 ring. Here we report structural features of F1 responsible for torque generation and the catalytic ability of the low-torque F0F1. (i) Deletion of one or two turns in the ?-helix in the C-terminal domain of catalytic ? subunit at the rotor/stator contact region generates mutant F1s, termed F1(1/2)s, that rotate with about half of the normal torque. This helix would support the helix-loop-helix structure acting as a solid “pushrod” to push the rotor ? subunit, but the short helix in F1(1/2)s would fail to accomplish this task. (ii) Three different half-torque F0F1(1/2)s were purified and reconstituted into proteoliposomes. They carry out ATP-driven proton pumping and build up the same small transmembrane ?pH, indicating that the final ?pH is directly related to the amount of torque. (iii) The half-torque F0F1(1/2)s can catalyze ATP synthesis, although slowly. The rate of synthesis varies widely among the three F0F1(1/2)s, which suggests that the rate reflects subtle conformational variations of individual mutants.

Usukura, Eiji; Suzuki, Toshiharu; Furuike, Shou; Soga, Naoki; Saita, Ei-ichiro; Hisabori, Toru; Kinosita, Kazuhiko; Yoshida, Masasuke

2012-01-01

102

Dynein ATPase pathway: ATP analogs and regulation by phosphorylation  

SciTech Connect

Three biochemical aspects of 22S dynein from Tetrahymena cilia have been investigated: its ATP binding polypeptides and the manner in which they bind ATP, its AMPPNP-induced dissociation from microtubules, and its phosphorylation. We have attempted to identify the polypeptides of dynein that bind ATP, i.e., the active site polypeptides, with the photoaffinity ATP analog 8-N{sub 3}ATP. The 8-N{sub 3}ATP has been shown to bind to dyneins active sites and in a manner similar to that of ATP. Upon irradiation, (2-{sup 3}H)8-N{sub 3}ATP covalently labels the three heavy chains, i.e., heads, which is detected by autoradiography of SDS PAG's. Thus, the three heads are considered to be the three active sites of dynein. AMPPNP is a nonhydrolyzable ATP analog which we have assayed for the ability to induce dynein dissociation from microtubules.

Chilcote, T.J.

1988-01-01

103

Clinical definitions of melioidosis.  

PubMed

Clinical definitions of melioidosis and inhalation-acquired melioidosis (Burkholderia pseudomallei infection) are described together with the evidence used to develop these definitions. Such definitions support accurate public health reporting, preparedness planning for deliberate B. pseudomallei release, design of experimental models, and categorization of naturally acquired melioidosis. PMID:23468355

Cheng, Allen C; Currie, Bart J; Dance, David A B; Funnell, Simon G P; Limmathurotsakul, Direk; Simpson, Andrew J H; Peacock, Sharon J

2013-03-01

104

A large conformational change in the putative ATP pyrophosphatase PF0828 induced by ATP binding  

PubMed Central

ATP pyrophosphatases (ATP PPases) are widely distributed in archaea and eukaryotes. They share an HUP domain at the N-terminus with a conserved PP-­motif that interacts with the phosphates of ATP. The PF0828 protein from Pyrococcus furiosus is a member of the ATP PPase superfamily and it also has a 100-residue C-terminal extension that contains a strictly conserved EGG(E/D)xE(T/S) motif, which has been named the EGT-motif. Here, crystal structures of PF0828 alone and in complex with ATP or AMP are reported. The HUP domain contains a central five-stranded ?-sheet that is surrounded by four helices, as in other related structures. The C-terminal extension forms a separate domain, named the EGT domain, which makes tight interactions with the HUP domain, bringing the EGT-motif near to the PP-motif and defining the putative active site of PF0828. Both motifs interact with the phosphate groups of ATP. A loop in the HUP domain undergoes a large conformational change to recognize the adenine base of ATP. In solution and in the crystal PF0828 is a dimer formed by the side-by-side arrangement of the HUP domains of the two monomers. The putative active site is located far from the dimer interface.

Forouhar, Farhad; Saadat, Nabila; Hussain, Munif; Seetharaman, Jayaraman; Lee, Insun; Janjua, Haleema; Xiao, Rong; Shastry, Ritu; Acton, Thomas B.; Montelione, Gaetano T.; Tong, Liang

2011-01-01

105

Microglial migration mediated by ATP-induced ATP release from lysosomes  

PubMed Central

Microglia are highly motile cells that act as the main form of active immune defense in the central nervous system. Attracted by factors released from damaged cells, microglia are recruited towards the damaged or infected site, where they are involved in degenerative and regenerative responses and phagocytotic clearance of cell debris. ATP release from damaged neural tissues has been suggested to mediate the rapid extension of microglial process towards the site of injury. However, the mechanisms of the long-range migration of microglia remain to be clarified. Here, we found that lysosomes in microglia contain abundant ATP and exhibit Ca2+-dependent exocytosis in response to various stimuli. By establishing an efficient in vitro chemotaxis assay, we demonstrated that endogenously-released ATP from microglia triggered by local microinjection of ATP?S is critical for the long-range chemotaxis of microglia, a response that was significantly inhibited in microglia treated with an agent inducing lysosome osmodialysis or in cells derived from mice deficient in Rab 27a (ashen mice), a small GTPase required for the trafficking and exocytosis of secretory lysosomes. These results suggest that microglia respond to extracellular ATP by releasing ATP themselves through lysosomal exocytosis, thereby providing a positive feedback mechanism to generate a long-range extracellular signal for attracting distant microglia to migrate towards and accumulate at the site of injury.

Dou, Ying; Wu, Hang-jun; Li, Hui-quan; Qin, Song; Wang, Yin-er; Li, Jing; Lou, Hui-fang; Chen, Zhong; Li, Xiao-ming; Luo, Qing-ming; Duan, Shumin

2012-01-01

106

Local detection of mechanically induced ATP release from bone cells with ATP microbiosensors.  

PubMed

The mechanically induced release of adenosine-5'-triphosphate (ATP) from osteoblastic cells (MC3T3-E1) was measured in real time. A stretching device integrated into scanning electrochemical microscopy was developed to apply controlled mechanical strain to MC3T3-E1 cells. For ATP secretion, a stepwise yet uniform mechanical stress was imposed onto MC3T3-E1 cells. The ATP biosensors were positioned at a distance of approximately 30-40 ?m above the cell surface. Calibration functions were recorded prior to the cell measurements and revealed a linear response up to 40 ?M with a sensitivity of 1-5pA/?M ATP. Stretching MC3T3-E1 cells up to 21% resulted in a concentration of 30.57±4.82 ?M of extracellular ATP (N=12) detected above the cell surface. As a control experiment, nifedipine, a L-type voltage sensitive calcium channel (L-VSCC) inhibitor was applied, which blocks Ca(2+)entry from the outer medium into the cell. Inhibition resulted in a significantly smaller amount of released ATP, i.e., 7.08±1.93 ?M ATP (N=10). Further control experiments with glucose microbiosensors did not yield significant changes of the baseline current (N=8). PMID:23384767

Hecht, Elena; Liedert, Astrid; Ignatius, Anita; Mizaikoff, Boris; Kranz, Christine

2013-01-11

107

Density functional calculations of ATP systems. 1. Crystalline ATP hydrates and related molecules.  

PubMed

Adenosine 5'-triphosphate (ATP) is an essential energy carrier in mammalian and other cells, and its hydrolysis to the diphosphate (ADP) in the presence of metal cations (e.g., Mg(2+) or Ca(2+)) is one of the most prevalent biochemical reactions. We describe here density functional (DF) calculations on closely related systems and compare the results with other calculations and available experimental data: Na(H2O)n +, Mg(H2O)n 2+, and Ca(H2O)n 2+ clusters (n = 1, 4-7), the crystalline pyrophosphates Mg(2)P(2)O(7).6H2O and alpha-CaNa(2)P(2)O(7).4H2O, and crystalline Na(2)ATP.3H2O. The last of these comprises asymmetric units of ATP dimers (monomers A and B) in a double-protonated state H(2)(ATP)(2-). The calculated structures agree well with available measurements and provide additional information, including the location of the H atoms. Analysis of the dipole moments of individual ATP monomers and their dimers shows that the crystal comprises blocks of opposing dipoles. Replacing one Na+ ion with Mg2+ or Ca2+ results in a significant elongation of the terminal bridging P-O bond. The calculations provide benchmarks for the use of DF methods in ATP systems and are used in the companion paper to study the hydrolysis of ATP at the active site of the protein actin. PMID:16610914

Akola, J; Jones, R O

2006-04-20

108

Welding III.  

ERIC Educational Resources Information Center

|Instructional objectives and performance requirements are outlined in this course guide for Welding III, an advanced course in arc welding offered at the Community College of Allegheny County to provide students with the proficiency necessary for industrial certification. The course objectives, which are outlined first, specify that students will…

Allegheny County Community Coll., Pittsburgh, PA.

109

Snapshots of the maltose transporter during ATP hydrolysis  

PubMed Central

ATP-binding cassette transporters are powered by ATP, but the mechanism by which these transporters hydrolyze ATP is unclear. In this study, four crystal structures of the full-length wild-type maltose transporter, stabilized by adenosine 5?-(?,?-imido)triphosphate or ADP in conjunction with phosphate analogs , , or , were determined to 2.2- to 2.4-? resolution. These structures led to the assignment of two enzymatic states during ATP hydrolysis and demonstrate specific functional roles of highly conserved residues in the nucleotide-binding domain, suggesting that ATP-binding cassette transporters catalyze ATP hydrolysis via a general base mechanism.

Oldham, Michael L.; Chen, Jue

2011-01-01

110

Polynucleotide phosphorylase and mitochondrial ATP synthase mediate reduction of arsenate to the more toxic arsenite by forming arsenylated analogues of ADP and ATP.  

PubMed

We have demonstrated that phosphorolytic-arsenolytic enzymes can promote reduction of arsenate (AsV) into the more toxic arsenite (AsIII) because they convert AsV into an arsenylated product in which the arsenic is more reducible by glutathione (GSH) or other thiols to AsIII than in inorganic AsV. We have also shown that mitochondria can rapidly reduce AsV in a process requiring intact oxidative phosphorylation and intramitochondrial GSH. Thus, these organelles might reduce AsV because mitochondrial ATP synthase, using AsV instead of phosphate, arsenylates ADP to ADP-AsV, which in turn is readily reduced by GSH. To test this hypothesis, we first examined whether the RNA-cleaving enzyme polynucleotide phosphorylase (PNPase), which can split poly-adenylate (poly-A) by arsenolysis into units of AMP-AsV (a homologue of ADP-AsV), could also promote reduction of AsV to AsIII in presence of thiols. Indeed, bacterial PNPase markedly facilitated formation of AsIII when incubated with poly-A, AsV, and GSH. PNPase-mediated AsV reduction depended on arsenolysis of poly-A and presence of a thiol. PNPase can also form AMP-AsV from ADP and AsV (termed arsenolysis of ADP). In presence of GSH, this reaction also facilitated AsV reduction in proportion to AMP-AsV production. Although various thiols did not influence the arsenolytic yield of AMP-AsV, they differentially promoted the PNPase-mediated reduction of AsV, with GSH being the most effective. Circumstantial evidence indicated that AMP-AsV formed by PNPase is more reducible to AsIII by GSH than inorganic AsV. Then, we demonstrated that AsV reduction by isolated mitochondria was markedly inhibited by an ADP analogue that enters mitochondria but is not phosphorylated or arsenylated. Furthermore, inhibitors of the export of ATP or ADP-AsV from the mitochondria diminished the increment in AsV reduction caused by adding GSH externally to these organelles whose intramitochondrial GSH had been depleted. Thus, whereas PNPase promotes reduction of AsV by incorporating it into AMP-AsV, the mitochondrial ATP synthase facilitates AsV reduction by forming ADP-AsV; then GSH can easily reduce these arsenylated nucleotides to AsIII. PMID:20457661

Németi, Balázs; Regonesi, Maria Elena; Tortora, Paolo; Gregus, Zoltán

2010-05-10

111

Chloroplast F0F1 ATP Synthase Imaged by Atomic Force Microscopy  

PubMed

The F0F1 ATP synthase of chloroplasts was imaged using atomic force microscopy (AFM) in contact mode under physiological conditions. Chloroplast (CF0F1) ATP synthases were reconstituted into liposomes. Liposomes were adsorbed on a mica surface where they spread and formed lipid bilayers containing CF0F1 ATP synthases which could be imaged. From these reconstituted CF0F1 ATP synthases, the CF1 part could be removed either by application of a chemical denaturant or less efficiently by mechanical stripping with the AFM tip. Embedded in the lipid bilayer were seen ring-like structures with a central dimple with outer diameters of 20 +/- 3 nm (chemical denaturant) and ca. 7 nm (mechanical stripping), respectively. Ring-like structures were also observed in a protein-free lipid bilayer. These had diameters of 30 +/- 5 nm and could be clearly distinguished from the structures observed after mechanical stripping. Hence, the ring-like structures observed after mechanical stripping might represent the intrinsic membrane domain CF0 or the oligomer of its subunit III. In addition, isolated CF1 adsorbed directly onto the mica surface was imaged. In accordance with the size known from electron microscopy, a diameter of 13 +/- 4 nm was measured. PMID:9245754

Neff; Tripathi; Middendorf; Stahlberg; Butt; Bamberg; Dencher

1997-07-01

112

Electric field driven torque in ATP synthase.  

PubMed

FO-ATP synthase (FO) is a rotary motor that converts potential energy from ions, usually protons, moving from high- to low-potential sides of a membrane into torque and rotary motion. Here we propose a mechanism whereby electric fields emanating from the proton entry and exit channels act on asymmetric charge distributions in the c-ring, due to protonated and deprotonated sites, and drive it to rotate. The model predicts a scaling between time-averaged torque and proton motive force, which can be hindered by mutations that adversely affect the channels. The torque created by the c-ring of FO drives the ?-subunit to rotate within the ATP-producing complex (F1) overcoming, with the aid of thermal fluctuations, an opposing torque that rises and falls with angular position. Using the analogy with thermal Brownian motion of a particle in a tilted washboard potential, we compute ATP production rates vs. proton motive force. The latter shows a minimum, needed to drive ATP production, which scales inversely with the number of proton binding sites on the c-ring. PMID:24040370

Miller, John H; Rajapakshe, Kimal I; Infante, Hans L; Claycomb, James R

2013-09-10

113

Extracellular ATP signaling and homeostasis in plant cells  

PubMed Central

Extracellular ATP (eATP) is now recognized as an important signaling agent in plant growth and defense response to environmental stimuli. eATP has dual functions in plant cell signaling, which is largely dependent on its concentration in the extracellular matrix (ECM). A lethal level of eATP (extremely low or high) causes cell death, whereas a moderate level of eATP benefits plant growth and development. Ecto-apyrases (Nucleoside Triphosphate-Diphosphohydrolase) help control the eATP concentrations in the ECM, and thus contributing to the mediation of plant growth and defense response upon environmental stress. In this review, we summarize eATP signaling in plants and highlight the correlation between eATP homeostasis control and programmed cell death.

Sun, Jian; Zhang, Chunlan; Zhang, Xuan; Deng, Shurong; Zhao, Rui; Shen, Xin; Chen, Shaoliang

2012-01-01

114

Findings from Advanced Technology Program's (ATP's) Survey of Joint Ventures.  

National Technical Information Service (NTIS)

The Advanced Technology Program (ATP) conducted a survey of all joint ventures that received an ATP award between 1991 and 2001. The survey was conducted to understand the motivations and impacts of joint venture collaborations. The findings show that the...

A. Wang J. O'Brien K. McTigue S. Shipp

2006-01-01

115

Endogenous ATP potentiates only vasopressin secretion from neurohypophysial terminals  

Microsoft Academic Search

Exogenous ATP induces inward currents and causes the release of arginine-vasopressin (AVP) from isolated neurohypophysial terminals (NHT); both effects are inhibited by the P2X2 and P2X3 antagonists, suramin and PPADS. Here we examined the role of endogenous ATP in the neurohypophysis. Stimulation of NHT caused the release of both AVP and ATP. ATP induced a potentiation in the stimulated release

Thomas K. Knott; Hector G. Marrero; Edward E. Custer; Jose R. Lemos

2008-01-01

116

Therapeutic Targeting of ATP7B in Ovarian Carcinoma  

Microsoft Academic Search

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.\\u000aEXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A

Lingegowda S Mangala; Vesna Zuzel; Rosemarie Schmandt; Erik S Leshane; Jyotsna B Halder; Guillermo N Armaiz-Pena; Whitney A Spannuth; Takemi Tanaka; Mian M K Shahzad; Yvonne G Lin; Alpa M Nick; Christopher G Danes; Jeong-Won Lee; Nicholas B Jennings; Pablo E Vivas-Mejia; Judith K Wolf; Robert L Coleman; Zahid H Siddik; Gabriel Lopez-Berestein; Svetlana Lutsenko; Anil K Sood

2009-01-01

117

ATP synthesis: the world's smallest wind-up toy.  

PubMed

ATP synthase contains two rotary motors coupled back-to-back: the protonmotive force-driven motor F0 pushes the ATP-driven motor F1 in reverse, causing it to synthesize ATP. Half of this process has now been reproduced in vitro, using tiny magnets instead of F0 to drive the reverse rotation of a single F1 molecule. PMID:15916941

Berry, Richard M

2005-05-24

118

Physiological levels of ATP Negatively Regulate Proteasome Function  

PubMed Central

Intracellular protein degradation by the ubiquitin-proteasome system is ATP-dependent and the optimal ATP concentration to activate proteasome function in vitro is ~100 ?M. Intracellular ATP levels are generally in the low millimolar range but ATP at a level within this range was shown to inhibit proteasome peptidase activities in vitro. Here we report new evidence that supports a hypothesis that intracellular ATP at the physiological levels bidirectionally regulates 26S proteasome proteolytic function in the cell. First, we confirmed that ATP exerted bidirectional regulation on the 26S proteasome in vitro, with the optimal ATP concentration (between 50–100 ?M) stimulating proteasome chymotrypsin-like activities. Second, we found that manipulating intracellular ATP levels also led to bidirectional changes in the levels of proteasome-specific protein substrates in cultured cells. Finally, measures to increase intracellular ATP enhanced, while decreasing intracellular ATP attenuated, the ability of proteasome inhibition to induce cell death. These data strongly suggest that endogenous ATP within the physiological concentration range can exert a negative impact on proteasome activities, allowing the cell to rapidly up-regulate proteasome activity upon ATP reduction under stress conditions.

Huang, Hongbiao; Zhang, Xiaoyan; Li, Shujue; Liu, Ningning; Lian, Wen; McDowell, Emily; Zhou, Ping; Zhao, Canguo; Guo, Haiping; Zhang, Change; Yang, Changshan; Wen, Guangmei; Dong, Xiaoxian; Lu, Li; Ma, Ningfang; Dong, Weihua; Dou, Q. Ping; Wang, Xuejun; Liu, Jinbao

2010-01-01

119

Bioanalytical Applications of Real-Time ATP Imaging via Bioluminescence.  

National Technical Information Service (NTIS)

The research discussed within involves the development of novel applications of real-time imaging of adenosine 5'-triphosphate (ATP). ATP was detected via bioluminescence and the firefly luciferase-catalyzed reaction of ATP and luciferin. The use of a mic...

J. A. Gruenhagen

2003-01-01

120

Renal Cell-to-Cell Communication via Extracellular ATP  

NSDL National Science Digital Library

In the kidney, macula densa cells communicate with the mesangial cell-afferent arteriolar smooth muscle cell complex through ATP signaling. This signaling process involves release of ATP across the macula densa basolateral membrane through a maxi anion channel and the interaction of ATP with purinergic P2 receptors.

MD Peter Komlosi (University of Alabama at Birmingham Departments of Medicine and Physiology, Division of Nephrology); Attila Fintha (University of Alabama Departments of Medicine and Physiology, Division of Nephrology); PhD P. Darwin Bell (University of Alabama Departments of Medicine and Physiology, Division of Nephrology)

2005-04-01

121

Evidence for Nuclear Control of the Expression of the atpA and atpB Chloroplast Genes in Chlamydomonas  

Microsoft Academic Search

We analyzed three nuclear mutants of Chlamydomonas reinhardtii altered in the expression of the chloroplast genes atpA or atpB coding for the a or p subunit of the chloroplast ATP synthase. These mutants revealed the existence of three nuclear products controlling the expression of the two chloroplast genes: the first one acts on the translation of the atpA transcript, and

Dominique Drapier; Jacqueline Girard-Bascou; FrancisAndre Wollman

1992-01-01

122

Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue  

Microsoft Academic Search

BACKGROUND: ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry

Virginia Ip; Johnson J Liu; Julian FB Mercer; Mark J McKeage

2010-01-01

123

High-definition television  

SciTech Connect

According to this report, high-definition television is the next generation in video technology. By increasing the number of scanning lines from 525 to over 1,000 high-definition television transmits an image that is wider than and twice as sharp as current television. This fact sheet contains information on 14 applications of high- definition television. Defense, medical, space exploration, and other uses are discussed. The report also presents the opinions of key industry officials on the effect that a high- definition television standard would have on potential applications of this technology.

Not Available

1990-01-01

124

Molecular analysis of Wilson patients: direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis.  

PubMed

ATP7B mutations result in Cu storage in the liver and brain in Wilson disease (WD). Atox1 and COMMD1 were found to interact with ATP7B and involved in copper transport in the hepatocyte. To understand the molecular etiology of WD, we analyzed ATP7B, Atox1 and COMMD1 genes. Direct sequencing of (i) ATP7B gene was performed in 112 WD patients to identify the spectrum of disease-causing mutations in the French population, (ii) Atox1 gene was performed to study the known polymorphism 5'UTR-99T>C in 78 WD patients with two ATP7B mutations and (iii) COMMD1 gene was performed to detect the nucleotide change c.492GAT>GAC. MLPA (Multiplex Ligation-dependent Probe Amplification) analysis was performed in WD patients presenting only one ATP7B mutation. Among our 112 WD unrelated patients, 83 different ATP7B gene mutations were identified, 27 of which were novel. Two ATP7B mutations were identified in 98 WD cases, and one mutation was identified in 14 cases. In two of these 14 WD patients, we identified the deletion of exon 4 of the ATP7B gene by MLPA technique. In 78 selected patients of the cohort with two mutations in ATP7B, we have examined genotype-phenotype correlation between the detected changes in Atox1 and COMMD1 genes, and the presentation of the WD patients. Based on the data of this study, no major role can be attributed to Atox1 and COMMD in the pathophysiology or clinical variation of WD. PMID:22677543

Bost, Muriel; Piguet-Lacroix, Guénaelle; Parant, François; Wilson, C M R

2012-06-05

125

Potentiation of cytokine induction of group IIA phospholipase A2 in rat mesangial cells by ATP and adenosine via the A2A adenosine receptor  

PubMed Central

In rat mesangial cells extracellular nucleotides were found to increase arachidonic acid release by a cytosolic phospholipase A2 through the P2Y2 purinergic receptor. In this study we investigated the effects of ATP and UTP on interleukin-1? (IL-1?)-induced mRNA expression and activity of group IIA phospholipase A2 (sPLA2-IIA) in rat mesangial cells. Treatment of cells for 24?h with extracellular ATP potentiated IL-1?-stimulated sPLA2-IIA induction, whereas UTP had no effect. We obtained the following evidence that the P2Y2 receptor is not involved in the potentiation of sPLA2-IIA induction: (i) ATP-?-S had no enhancing effect; (ii) suramin, a P2 receptor antagonist, did not inhibit ATP-mediated potentiation; (iii) inhibition of degradation of extracellular nucleotides by the 5?-ectonucleotidase inhibitor AOPCP did not enhance sPLA2-IIA induction and (iv) adenosine deaminase treatment completely abolished the ATP-mediated potentiation of sPLA2-IIA induction. In contrast, treatment of mesangial cells with adenosine or the A2A receptor agonist CGS 21680 mimicked the effects of ATP in enhancing IL-1?-stimulated sPLA2-IIA induction, whereas the specific A2A receptor antagonist ZM 241385 completely abolished the potentiating effect of ATP or adenosine. The protein kinase A inhibitor Rp-8-Br-cyclic AMPS dose-dependently inhibited the enhancing effect of ATP or adenosine indicating the participation of an adenosine receptor-mediated cyclic AMP-dependent signalling pathway. These data indicate that ATP mediates proinflammatory long-term effects in rat mesangial cells via its degradation product adenosine through the A2A receptor resulting in potentiation of sPLA2-IIA induction.

Scholz-Pedretti, Kirsten; Pfeilschifter, Josef; Kaszkin, Marietta

2001-01-01

126

A New Type of Na+-Driven ATP Synthase Membrane Rotor with a Two-Carboxylate Ion-Coupling Motif  

PubMed Central

The anaerobic bacterium Fusobacterium nucleatum uses glutamate decarboxylation to generate a transmembrane gradient of Na+. Here, we demonstrate that this ion-motive force is directly coupled to ATP synthesis, via an F1Fo-ATP synthase with a novel Na+ recognition motif, shared by other human pathogens. Molecular modeling and free-energy simulations of the rotary element of the enzyme, the c-ring, indicate Na+ specificity in physiological settings. Consistently, activity measurements showed Na+ stimulation of the enzyme, either membrane-embedded or isolated, and ATP synthesis was sensitive to the Na+ ionophore monensin. Furthermore, Na+ has a protective effect against inhibitors targeting the ion-binding sites, both in the complete ATP synthase and the isolated c-ring. Definitive evidence of Na+ coupling is provided by two identical crystal structures of the c11 ring, solved by X-ray crystallography at 2.2 and 2.6 Å resolution, at pH 5.3 and 8.7, respectively. Na+ ions occupy all binding sites, each coordinated by four amino acids and a water molecule. Intriguingly, two carboxylates instead of one mediate ion binding. Simulations and experiments demonstrate that this motif implies that a proton is concurrently bound to all sites, although Na+ alone drives the rotary mechanism. The structure thus reveals a new mode of ion coupling in ATP synthases and provides a basis for drug-design efforts against this opportunistic pathogen.

Schulz, Sarah; Iglesias-Cans, Marina; Krah, Alexander; Yildiz, Ozkan; Leone, Vanessa; Matthies, Doreen; Cook, Gregory M.

2013-01-01

127

Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5) P?.  

PubMed

Transient receptor potential vanilloid 6 (TRPV6) channels play an important role in Ca(2+) absorption in the intestines. Both phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] and cytoplasmic ATP have been proposed to be important for maintaining TRPV6 activity. To evaluate whether PtdIns(4,5)P(2) and ATP affect channel activity directly or indirectly, we have used a dual approach, examining channel activity in excised patches and planar lipid bilayers. In excised inside-out patch-clamp measurements, ATP reactivated the human TRPV6 channels after current rundown only in the presence of Mg(2+). The effect of MgATP was inhibited by 3 structurally different compounds that inhibit type III phosphatidylinositol 4-kinases (PI4Ks). PtdIns(4,5)P(2) also activated TRPV6 in excised patches, while its precursor PtdIns(4)P had only minimal effect. These data demonstrate that MgATP provides substrate for lipid kinases, allowing the resynthesis of PtdIns(4,5)P(2). To determine whether PtdIns(4,5)P(2) is a direct activator of TRPV6, we purified and reconstituted the channel protein in planar lipid bilayers. The reconstituted channel showed high activity in the presence of PtdIns(4,5)P(2), while PtdIns(4)P induced only minimal activity. Our data establish PtdIns(4,5)P(2) as a direct activator of TRPV6 and demonstrate that intracellular ATP regulates the channel indirectly as a substrate for type III PI4Ks. PMID:21810903

Zakharian, Eleonora; Cao, Chike; Rohacs, Tibor

2011-08-02

128

Therapeutic lifestyle change and Adult Treatment Panel III: evidence then and now.  

PubMed

The Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III) has an extensive section on nonpharmacologic therapy for those with abnormal blood lipids. ATP III focused on the high-saturated fat atherogenic diet, obesity, and sedentary lifestyle and recommended a program of therapeutic lifestyle change (TLC). This review discusses several issues, including 1) why ATP III changed from the Step I and Step II diets to TLC; 2) the benefits of keeping trans fatty acid intake low and the addition of viscous fiber and plant stanol/sterol esters to reduce low-density lipoprotein cholesterol beyond that seen with the Step II diet; 3) the de-emphasis on total fat and a sharper focus on the kinds of fat ingested in the new guidelines; 4) the endorsement of regular physical activity and weight loss as important first steps in reversing the unwanted metabolic effects of the metabolic syndrome; and 5) the emphasis of health-promoting aspects of the diet that include, among other things, fish and omega-3 fatty acids. At all stages of TLC, ATP III encourages the referral to registered dietitians or other qualified nutritionists for medical nutrition therapy. TLC and the ATP III guidelines should provide guidance to practitioners who wish to get low-density lipoprotein cholesterol to goal (whether or not drugs are used), prevent or treat the metabolic syndrome, and improve the overall health of the patient. PMID:12361490

Stone, Neil J; Van Horn, Linda

2002-11-01

129

7 CFR 3300.4 - Definitions.  

Code of Federal Regulations, 2013 CFR

...EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION...Street, SW., Washington, DC 20250. ATP means the Agreement on the International...Equipment to be Used for Such Carriage (ATP), and the annexes and appendices...

2013-01-01

130

7 CFR 3300.4 - Definitions.  

Code of Federal Regulations, 2010 CFR

...EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION...Street, SW., Washington, DC 20250. ATP means the Agreement on the International...Equipment to be Used for Such Carriage (ATP), and the annexes and appendices...

2009-01-01

131

7 CFR 3300.4 - Definitions.  

Code of Federal Regulations, 2010 CFR

...EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION...Street, SW., Washington, DC 20250. ATP means the Agreement on the International...Equipment to be Used for Such Carriage (ATP), and the annexes and appendices...

2010-01-01

132

Luminescense Determination of Cellular ATP in Cow's Milk for Mastitis Screening (Luminesnsbestamning av Cellular ATP i Komjolk for Screening Juverinflammation).  

National Technical Information Service (NTIS)

For the purpose of determining the possibility of using cellular ATP in cow's milk as a fast diagnostic test for mastitis conditions for such analysis were studied by means of the ATP-specific firefly luciferase. A simplified method of extracting ATP from...

T. Olsson K. Sandstedt O. Holmberg A. Thore

1980-01-01

133

Clostridium pasteurianum F1Fo ATP Synthase: Operon, Composition, and Some Properties  

Microsoft Academic Search

The atp operon encoding F1Fo ATP synthase in the fermentative obligate anaerobic bacterium Clostridium pasteurianum was sequenced. It consisted of nine genes arranged in the order atpI(i), atpB(a), atpE(c), atpF(b), atpH(), atpA(), atpG(), atpD(), and atpC(), which was identical to that found in many bacteria. Reverse transcription-PCR confirmed the presence of the transcripts of all nine genes. The amount of

Amaresh Das; Lars G. Ljungdahl

2003-01-01

134

ATP synthase: activating versus catalytic proton transfer.  

PubMed

ATP synthase (F-ATPase) of chloroplasts, CF0CF1, is both activated and driven by transmembrane protonmotive force. We dichotomized between activating and driving proton transfer by specific inhibitors, tentoxin and venturicidin. Thylakoids membranes were submitted to voltage steps (by flashing light) superimposed to a steady pH-difference. Transient proton intake, transfer and release by CF0CF1 was monitored by spectroscopic probes. Both activities, activation and catalysis, required all three partial reactions of the proton, however, activating proton transfer rose first (monophasically, tau 1/2 approximately 15 ms) followed by another phase of equal magnitude with a time lag of about 15 ms. Both types of consecutive proton transfer reactions contribute free energy for ATP synthesis. PMID:7828724

Groth, G; Junge, W

1995-01-23

135

The mitochondrial K(ATP) channel--fact or fiction?  

PubMed

The mitochondrial ATP-dependent K(+) channel (mitoK(ATP)) is widely considered by many to play a central role in cardioprotection by ischemic and pharmacological preconditioning and by ischemic postconditioning. Nevertheless, several laboratories have questioned the existence of mitoK(ATP). This article summarizes the evidence for and against and addresses two key questions: How strong is the evidence for the presence of a K(ATP) channel in mitochondria? Are the pharmacological agents used to modulate mitoK(ATP) activity sufficiently specific to allow the role of these channels in cardioprotection to be established? PMID:22240339

Garlid, Keith D; Halestrap, Andrew P

2012-01-02

136

ATP-dependent human RISC assembly pathways  

Microsoft Academic Search

The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA–mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1–4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here

Mayuko Yoda; Tomoko Kawamata; Zain Paroo; Xuecheng Ye; Shintaro Iwasaki; Qinghua Liu; Yukihide Tomari

2009-01-01

137

Continuous Measurements of ATP Secretion in Vivo  

Microsoft Academic Search

Blood was withdrawn continuously from femoral veins of anesthetized rabbits at a rate of 0.07 ml\\/min. Sodium citrate was pumped into the blood to prevent coagulation, and luciferin-luciferase reagent was added to permit the continuous detection of extracellular ATP. Subsequently, the red blood cells were lysed and the platelet count was recorded continuously. Injection of platelet activating factor or collagen

J. Bryan Smith; Sandra E. Burke; Allan M. Lefer; Arthur Freilich

1984-01-01

138

Yeast ADP/ATP Carrier Isoform 2  

PubMed Central

The mitochondrial ADP/ATP carrier, or Ancp, is a member of the mitochondrial carrier family responsible for exchanging ADP and ATP across the mitochondrial inner membrane. ADP/ATP transport involves Ancp switching between two conformational states. These can be analyzed using specific inhibitors, carboxyatractyloside (CATR) and bongkrekic acid (BA). The high resolution three-dimensional structure of bovine Anc1p (bAnc1p), as a CATR-carrier complex, has been solved. However, because the structure of the BA-carrier complex has not yet been determined, the detailed mechanism of transport remains unknown. Recently, sample processing for hydrogen/deuterium exchange experiments coupled to mass spectrometry was improved, providing novel insights into bAnc1p conformational transitions due to inhibitor binding. In this work we performed both hydrogen/deuterium exchange-mass spectrometry experiments and genetic manipulations. Because these are very difficult to apply with bovine Anc1p, we used Saccharomyces cerevisiae Anc isoform 2 (ScAnc2p). Significant differences in solvent accessibility were observed throughout the amino acid sequence for ScAnc2p complexed to either CATR or BA. Interestingly, in detergent solution, the conformational dynamics of ScAnc2p were dissimilar to those of bAnc1p, in particular for the upper half of the cavity, toward the intermembrane space, and the m2 loop, which is thought to be easily accessible to the solvent from the matrix in bAnc1p. Our study then focused on the methionyl residues of the Ancp signature sequence, RRRMMM. All our results indicate that the methionine cluster is involved in the ADP/ATP transport mechanism and confirm that the Ancp cavity is a highly dynamic structure.

Clemencon, Benjamin; Rey, Martial; Trezeguet, Veronique; Forest, Eric; Pelosi, Ludovic

2011-01-01

139

Sphingomyelinase Treatment Induces ATP-independent Endocytosis  

PubMed Central

ATP hydrolysis has been regarded as a general requirement for internalization processes in mammalian cells. We found, however, that treatment of ATP-depleted macrophages and fibroblasts with exogenous sphingomyelinase (SMase) rapidly induces formation of numerous vesicles that pinch off from the plasma membrane; the process is complete within 10 min after adding SMase. By electron microscopy, the SMase-induced vesicles are ?400 nm in diameter and lack discernible coats. 15–30% of plasma membrane is internalized by SMase treatment, and there is no detectable enrichment of either clathrin or caveolin in these vesicles. When ATP is restored to the cells, the SMase-induced vesicles are able to deliver fluid-phase markers to late endosomes/lysosomes and return recycling receptors, such as transferrin receptors, back to the plasma membrane. We speculate that hydrolysis of sphingomyelin on the plasma membrane causes inward curvature and subsequent fusion to form sealed vesicles. Many cell types express a SMase that can be secreted or delivered to endosomes and lysosomes. The hydrolysis of sphingomyelin by these enzymes is activated by several signaling pathways, and this may lead to formation of vesicles by the process described here.

Zha, Xiaohui; Pierini, Lynda M.; Leopold, Philip L.; Skiba, Paul J.; Tabas, Ira; Maxfield, Frederick R.

1998-01-01

140

Proteomic Analysis of Extracellular ATP-Regulated Proteins Identifies ATP Synthase ?-Subunit as a Novel Plant Cell Death Regulator*  

PubMed Central

Extracellular ATP is an important signal molecule required to cue plant growth and developmental programs, interactions with other organisms, and responses to environmental stimuli. The molecular targets mediating the physiological effects of extracellular ATP in plants have not yet been identified. We developed a well characterized experimental system that depletes Arabidopsis cell suspension culture extracellular ATP via treatment with the cell death-inducing mycotoxin fumonisin B1. This provided a platform for protein profile comparison between extracellular ATP-depleted cells and fumonisin B1-treated cells replenished with exogenous ATP, thus enabling the identification of proteins regulated by extracellular ATP signaling. Using two-dimensional difference in-gel electrophoresis and matrix-assisted laser desorption-time of flight MS analysis of microsomal membrane and total soluble protein fractions, we identified 26 distinct proteins whose gene expression is controlled by the level of extracellular ATP. An additional 48 proteins that responded to fumonisin B1 were unaffected by extracellular ATP levels, confirming that this mycotoxin has physiological effects on Arabidopsis that are independent of its ability to trigger extracellular ATP depletion. Molecular chaperones, cellular redox control enzymes, glycolytic enzymes, and components of the cellular protein degradation machinery were among the extracellular ATP-responsive proteins. A major category of proteins highly regulated by extracellular ATP were components of ATP metabolism enzymes. We selected one of these, the mitochondrial ATP synthase ?-subunit, for further analysis using reverse genetics. Plants in which the gene for this protein was knocked out by insertion of a transfer-DNA sequence became resistant to fumonisin B1-induced cell death. Therefore, in addition to its function in mitochondrial oxidative phosphorylation, our study defines a new role for ATP synthase ?-subunit as a pro-cell death protein. More significantly, this protein is a novel target for extracellular ATP in its function as a key negative regulator of plant cell death.

Chivasa, Stephen; Tome, Daniel F. A.; Hamilton, John M.; Slabas, Antoni R.

2011-01-01

141

Seclusion: Definitional interpretations  

Microsoft Academic Search

Seclusion of psychiatric patients means different things to different people and different organizations. Without a clear definitional framework misunderstanding can occur and comparative analyses are made difficult. In an attempt to establish universal themes 166 international articles and books on seclusion were reviewed and their definitional interpretations evaluated. The results highlight a wide disparity between studies and there is little

Tom Mason

1992-01-01

142

TEDS Report Definitions.  

National Technical Information Service (NTIS)

This report provides definitions for terms used in The TEDS Report, which presents findings from the Treatment Episode Data Set (TEDS). These definitions will also be available on the OAS website. In the future, The TEDS Report will refer readers to this ...

2008-01-01

143

Inland Wetland Definitions  

Microsoft Academic Search

This work is the result of a year-long study of the definitions of inland wetlands in which definitions from geology, hydrogeology, hydrology, pedology, biology, systems ecology, sociology, economics, political sciences, public health and law were considered. Of these, geology, hydrogeology, hydrology, biology, systems ecology and economics are discussed in detail in this report and used in writing a final theoretical

Michael W Lefor; William C Kennard

1977-01-01

144

Mycobacterium tuberculosis universal stress protein Rv2623 regulates bacillary growth by ATP-Binding: requirement for establishing chronic persistent infection.  

PubMed

Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i) M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii) Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii) Rv2623 binds ATP; and iv) the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection. PMID:19478878

Drumm, Joshua E; Mi, Kaixia; Bilder, Patrick; Sun, Meihao; Lim, Jihyeon; Bielefeldt-Ohmann, Helle; Basaraba, Randall; So, Melvin; Zhu, Guofeng; Tufariello, Joann M; Izzo, Angelo A; Orme, Ian M; Almo, Steve C; Leyh, Thomas S; Chan, John

2009-05-29

145

Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP-Binding: Requirement for Establishing Chronic Persistent Infection  

PubMed Central

Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosis universal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-Å-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i) M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii) Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii) Rv2623 binds ATP; and iv) the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

Bilder, Patrick; Sun, Meihao; Lim, Jihyeon; Bielefeldt-Ohmann, Helle; Basaraba, Randall; So, Melvin; Zhu, Guofeng; Tufariello, JoAnn M.; Izzo, Angelo A.; Orme, Ian M.; Almo, Steve C.; Leyh, Thomas S.; Chan, John

2009-01-01

146

Release of ATP induced by hypertonic solutions in Xenopus oocytes  

PubMed Central

ATP mediates intercellular communication. Mechanical stress and changes in cell volume induce ATP release from various cell types, both secretory and non-secretory. In the present study, we stressed Xenopus oocytes with a hypertonic solution enriched in mannitol (300 mm). We measured simultaneously ATP release and ionic currents from a single oocyte. A decrease in cell volume, the activation of an inward current and ATP release were coincident. We found two components of ATP release: the first was associated with granule or vesicle exocytosis, because it was inhibited by tetanus neurotoxin, and the second was related to the inward current. A single exponential described the correlation between ATP release and the hypertonic-activated current. Gadolinium ions, which block mechanically activated ionic channels, inhibited the ATP release and the inward current but did not affect the decrease in volume. Oocytes expressing CFTR (cystic fibrosis transmembrane regulator) released ATP under hypertonic shock, but ATP release was significantly inhibited in the first component: that related to granule exocytosis. Since the ATP measured is the balance between ATP release and ATP degradation by ecto-enzymes, we measured the nucleoside triphosphate diphosphohydrolase (NTPDase) activity of the oocyte surface during osmotic stress, as the calcium-dependent hydrolysis of ATP, which was inhibited by more than 50 % in hypertonic conditions. The best-characterized membrane protein showing NTPDase activity is CD39. Oocytes injected with an antisense oligonucleotide complementary to CD39 mRNA released less ATP and showed a lower amplitude in the inward current than those oocytes injected with water.

Aleu, Jordi; Martin-Satue, Mireia; Navarro, Piedad; de Lara, Ivanna Perez; Bahima, Laia; Marsal, Jordi; Solsona, Carles

2003-01-01

147

Calcium binding to the subunit c of E. coli ATP-synthase and possible functional implications in energy coupling  

Microsoft Academic Search

The 8-kDa subunit c of theE. coli F0 ATP-synthase proton channel was tested for Ca++ binding activity using a45Ca++ ligand blot assay after transferring the protein from SDS-PAGE gels onto polyvinyl difluoride membranes. The purified subunit c binds45Ca++ strongly with Ca++ binding properties very similar to those of the 8-kDa CF0 subunit III of choloroplast thylakoid membranes. The N-terminal f-Met

Stanislav D. Zakharov; Xia Li; Taya P. Red'ko; Richard A. Dilley

1996-01-01

148

Kinetic mechanism of the dimeric ATP sulfurylase from plants  

PubMed Central

In plants, sulfur must be obtained from the environment and assimilated into usable forms for metabolism. ATP sulfurylase catalyses the thermodynamically unfavourable formation of a mixed phosphosulfate anhydride in APS (adenosine 5?-phosphosulfate) from ATP and sulfate as the first committed step of sulfur assimilation in plants. In contrast to the multi-functional, allosterically regulated ATP sulfurylases from bacteria, fungi and mammals, the plant enzyme functions as a mono-functional, non-allosteric homodimer. Owing to these differences, here we examine the kinetic mechanism of soybean ATP sulfurylase [GmATPS1 (Glycine max (soybean) ATP sulfurylase isoform 1)]. For the forward reaction (APS synthesis), initial velocity methods indicate a single-displacement mechanism. Dead-end inhibition studies with chlorate showed competitive inhibition versus sulfate and non-competitive inhibition versus APS. Initial velocity studies of the reverse reaction (ATP synthesis) demonstrate a sequential mechanism with global fitting analysis suggesting an ordered binding of substrates. ITC (isothermal titration calorimetry) showed tight binding of APS to GmATPS1. In contrast, binding of PPi (pyrophosphate) to GmATPS1 was not detected, although titration of the E•APS complex with PPi in the absence of magnesium displayed ternary complex formation. These results suggest a kinetic mechanism in which ATP and APS are the first substrates bound in the forward and reverse reactions, respectively.

Ravilious, Geoffrey E.; Herrmann, Jonathan; Goo Lee, Soon; Westfall, Corey S.; Jez, Joseph M.

2013-01-01

149

Mitochondria as ATP consumers: Cellular treason in anoxia  

PubMed Central

In anoxia, mitochondria change from being ATP producers to potentially powerful ATP consumers. This change occurs, because the mitochondrial F1F0-ATPase begins to hydrolyze ATP to avoid the collapse of the proton motive force. Species that can survive prolonged periods of O2 lack must limit such ATP use; otherwise, this process would dominate glycolytic metabolism and threaten ATP delivery to essential ATP-consuming processes of the cell (e.g., ion-motive ATPases). There are two ways to limit ATP hydrolysis by the F1F0-ATPase, namely (i) reduction of the proton conductance of the mitochondrial inner membrane and (ii) inhibition of the enzyme. We assessed these two possibilities by using intact mitochondria isolated from the skeletal muscle of anoxia-tolerant frogs. Our results show that proton conductance is unaltered between normoxia and anoxia. However, ATP use by the F1F0-ATPase is limited in anoxia by a profound inhibition of the enzyme. Even so, ATP use by the F1F0-ATPase might account for ?9% of the ATP turnover in anoxic frog skeletal muscle.

St-Pierre, Julie; Brand, Martin D.; Boutilier, Robert G.

2000-01-01

150

Coupled ATP and potassium efflux from intercalated cells  

PubMed Central

Increased flow in the distal nephron induces K secretion through the large-conductance, calcium-activated K channel (BK), which is primarily expressed in intercalated cells (IC). Since flow also increases ATP release from IC, we hypothesized that purinergic signaling has a role in shear stress (?; 10 dynes/cm2) -induced, BK-dependent, K efflux. We found that 10 ?M ATP led to increased IC Ca concentration, which was significantly reduced in the presence of the P2 receptor blocker suramin or calcium-free buffer. ATP also produced BK-dependent K efflux, and IC volume decrease. Suramin inhibited ?-induced K efflux, suggesting that K efflux is at least partially dependent on purinergic signaling. BK-?4 small interfering (si) RNA, but not nontarget siRNA, decreased ATP secretion and both ATP-dependent and ?-induced K efflux. Similarly, carbenoxolone (25 ?M), which blocks connexins, putative ATP pathways, blocked ?-induced K efflux and ATP secretion. Compared with BK-?4?/? mice, wild-type mice with high distal flows exhibited significantly more urinary ATP excretion. These data demonstrate coupled electrochemical efflux between K and ATP as part of the mechanism for ?-induced ATP release in IC.

Holtzclaw, J. David; Cornelius, Ryan J.; Hatcher, Lori I.

2011-01-01

151

Kinetic mechanism of the dimeric ATP sulfurylase from plants.  

PubMed

In plants, sulfur must be obtained from the environment and assimilated into usable forms for metabolism. ATP sulfurylase catalyses the thermodynamically unfavourable formation of a mixed phosphosulfate anhydride in APS (adenosine 5'-phosphosulfate) from ATP and sulfate as the first committed step of sulfur assimilation in plants. In contrast to the multi-functional, allosterically regulated ATP sulfurylases from bacteria, fungi and mammals, the plant enzyme functions as a mono-functional, non-allosteric homodimer. Owing to these differences, here we examine the kinetic mechanism of soybean ATP sulfurylase [GmATPS1 (Glycine max (soybean) ATP sulfurylase isoform 1)]. For the forward reaction (APS synthesis), initial velocity methods indicate a single-displacement mechanism. Dead-end inhibition studies with chlorate showed competitive inhibition versus sulfate and non-competitive inhibition versus APS. Initial velocity studies of the reverse reaction (ATP synthesis) demonstrate a sequential mechanism with global fitting analysis suggesting an ordered binding of substrates. ITC (isothermal titration calorimetry) showed tight binding of APS to GmATPS1. In contrast, binding of PPi (pyrophosphate) to GmATPS1 was not detected, although titration of the E•APS complex with PPi in the absence of magnesium displayed ternary complex formation. These results suggest a kinetic mechanism in which ATP and APS are the first substrates bound in the forward and reverse reactions, respectively. PMID:23789618

Ravilious, Geoffrey E; Herrmann, Jonathan; Goo Lee, Soon; Westfall, Corey S; Jez, Joseph M

2013-07-25

152

Does hepatic ATP depletion impair glycine conjugation in vivo?  

PubMed

Conjugation with glycine, a reaction important in the elimination of carboxylic acids (e.g. benzoic and salicylic acids), takes place in hepatic mitochondria and uses ATP, coenzyme A, and glycine. Although normal ATP supply does not limit glycine conjugation in vivo (Gregus, Z., et al., Drug Metab. Dispos. 20, 234, 1992), ATP deficiency may impair it. This hypothesis was tested by examining the effect of ATP depletors (oligomycin, fructose, and ethionine) on glycine conjugation and elimination of benzoic acid in rats. Pretreatment with the mitochondrial ATP synthesis inhibitor oligomycin (0.5-2 mg/kg, intraportally) decreased glycine conjugation of benzoic acid markedly and in a dose-dependent manner, as indicated by the delayed elimination of benzoate and delayed appearance of benzoylglycine in blood. Oligomycin also dramatically diminished urinary excretion of benzoylglycine, because it inhibited not only formation of benzoylglycine from benzoate, but also the renal transport of benzoylglycine. Treatment with fructose (a consumer of both cytosolic and mitochondrial ATP) or ethionine (a consumer of cytosolic ATP) depleted hepatic ATP from approximately 2.5 micromol/g to levels comparable with those observed after administration of 1 mg/kg oligomycin (approximately 1.2 micromol/g). Despite this, elimination of benzoate and formation of benzoylglycine were decreased less by fructose than by oligomycin and only negligibly by ethionine. ATP depletors did not influence hepatic glycine levels, and only oligomycin lowered coenzyme A levels in liver. However, the oligomycin-induced decline of hepatic coenzyme A levels was delayed, contrary to impairment of glycine conjugation, which was almost immediate. In summary, impairment of benzoylglycine formation by ATP depletors apparently correlates with their capacity to diminish ATP levels in hepatic mitochondria (i.e. at the site of glycine conjugation). These observations suggest that limited availability of mitochondrial (but not cytosolic) ATP reduces glycine conjugation capacity. Therefore, mitochondrium toxic agents and pathological mitochondrial injuries acting in liver may compromise glycine conjugation by decreasing ATP supply. PMID:8971141

Gregus, Z; Fekete, T; Halászi, E; Klaassen, C D

1996-12-01

153

ATP-dependent interaction of the cytosolic domains of the inwardly rectifying K+ channel Kir6.2 revealed by fluorescence resonance energy transfer  

PubMed Central

ATP-sensitive K+ (KATP) channels play important roles in the regulation of membrane excitability in many cell types. ATP inhibits channel activity by binding to a specific site formed by the N and C termini of the pore-forming subunit, Kir6.2, but the structural changes associated with this interaction remain unclear. Here, we use fluorescence resonance energy transfer (FRET) to study the ATP-dependent interaction between the N and C termini of Kir6.2 using a construct bearing fused cyan and yellow fluorescent proteins (ECFP-Kir6.2-EYFP). When expressed in human embryonic kidney cells, ECFP-Kir6.2-EYFP/SUR1 channels displayed FRET that was augmented by agonist stimulation and diminished by metabolic poisoning. Addition of ATP to permeabilized cells or isolated plasma membrane sheets increased FRET. FRET changes were abolished by Kir6.2 mutations that altered ATP-dependent channel closure and channel gating. In the wild-type channel, the ATP concentrations, which increased FRET (EC50 = 1.36 mM), were significantly higher than those causing channel inhibition (IC50 = 0.29 mM). Demonstrating the existence of intermolecular interactions, a dimeric construct comprising two molecules of Kir6.2 linked head-to-tail (ECFP-Kir6.2-Kir6.2-EYFP) displayed less FRET than the monomer in the absence of nucleotide but still exhibited ATP-dependent FRET increases (EC50 = 1.52 mM) and channel inhibition. We conclude that binding of ATP to Kir6.2, (i) alters the interaction between the N- and C-terminal domains, (ii) probably involves both intrasubunit and intersubunit interactions, (iii) reflects ligand binding not channel gating, and (iv) occurs in intact cells when subplasmalemmal [ATP] changes in the millimolar range.

Tsuboi, Takashi; Lippiat, Jonathan D.; Ashcroft, Frances M.; Rutter, Guy A.

2004-01-01

154

A study of spinach chloroplast ATP synthase  

Microsoft Academic Search

New heterobifunctional photoaffinity cross-linking reagents, 6-maleimido-N-(4-benzoylphenyl)hexanamide, 12-maleimido-N-(4-benzoylphenyl) dodecanamide, and 12-(¹⁴C)maleimido-N-(4-benzoylphenyl) dodecanamide, have been synthesized to investigate the mechanism of ATP hydrolysis by the soluble portion of the DSA, chloroplast coupling factor one (CFâ). The cross-linkers prevent major movements of the γ polypeptide with respect to the α and β polypeptides, but permit some flexibility in the enzyme structure. When â¼50%

Musier-Forsyth

1989-01-01

155

Definition of the Mesoscale  

NSDL National Science Digital Library

This module provides a working definition of mesoscale meteorology. The module briefly touches on many topics crucial to forecasting mesoscale weather phenomena, such as non-hydrostatic processes, the importance of terrain, NWP model resolution, and impact on sensible weather.

Spangler, Tim

1999-05-01

156

1 Purpose and Definitions  

Center for Food Safety and Applied Nutrition (CFSAN)

Text Version... This Code establishes definitions; sets standards for ... (b) A FOOD ingredient that contains protein derived from a ... (1) Any domesticated bird (chickens ... More results from www.fda.gov/downloads/food/guidanceregulation

157

Genomic definition of species  

SciTech Connect

The subject of this paper is the definition of species based on the assumption that genome is the fundamental level for the origin and maintenance of biological diversity. For this view to be logically consistent it is necessary to assume the existence and operation of the new law which we call genome law. For this reason the genome law is included in the explanation of species phenomenon presented here even if its precise formulation and elaboration are left for the future. The intellectual underpinnings of this definition can be traced to Goldschmidt. We wish to explore some philosophical aspects of the definition of species in terms of the genome. The point of proposing the definition on these grounds is that any real advance in evolutionary theory has to be correct in both its philosophy and its science.

Crkvenjakov, R.; Drmanac, R.

1991-07-01

158

Evidence for Nuclear Control of the Expression of the atpA and atpB Chloroplast Genes in Chlamydomonas.  

PubMed Central

We analyzed three nuclear mutants of Chlamydomonas reinhardtii altered in the expression of the chloroplast genes atpA or atpB coding for the [alpha] or [beta] subunit of the chloroplast ATP synthase. These mutants revealed the existence of three nuclear products controlling the expression of the two chloroplast genes: the first one acts on the translation of the atpA transcript, and the two others act specifically on the stability of either the atpB or the atpA mRNAs. The nuclear mutation responsible for the decreased stability of the atpB mRNA prevented translation of the corresponding polypeptide. In contrast, the mutation responsible for the decreased stability of the atpA mRNA had limited effect on the translation of the [alpha] subunit, thereby allowing its accumulation and assembly in an active ATP synthase. Although acting originally on the expression of only one of the two main coupling factor 1 subunits, the three mutations caused a change in the translation rate of the other subunit, as viewed in 5-min pulse labeling experiments. This is indicative of a concerted expression of the [alpha] and [beta] subunits at an early post-translational step, or during translation, that may be critical for the assembly of the chloroplast ATP synthase.

Drapier, D; Girard-Bascou, J; Wollman, FA

1992-01-01

159

Are rod outer segment ATP-ase and ATP-synthase activity expression of the same protein?  

PubMed

Vertebrate retinal rod outer segments (OS) consist of a stack of disks surrounded by the plasma membrane, where phototransduction takes place. Energetic metabolism in rod OS remains obscure. Literature described a so-called Mg(2+)-dependent ATPase activity, while our previous results demonstrated the presence of oxidative phosphorylation (OXPHOS) in OS, sustained by an ATP synthetic activity. Here we propose that the OS ATPase and ATP synthase are the expression of the same protein, i.e., of F1Fo-ATP synthase. Imaging on bovine retinal sections showed that some OXPHOS proteins are expressed in the OS. Biochemical data on bovine purified rod OS, characterized for purity, show an ATP synthase activity, inhibited by classical F1Fo-ATP synthase inhibitors. Moreover, OS possess a pH-dependent ATP hydrolysis, inhibited by pH values below 7, suggestive of the functioning of the inhibitor of F1 (IF1) protein. WB confirmed the presence of IF1 in OS, substantiating the expression of F1Fo ATP synthase in OS. Data suggest that the OS F1Fo ATP synthase is able to hydrolyze or synthesize ATP, depending on in vitro or in vivo conditions and that the role of IF1 would be pivotal in the prevention of the reversal of ATP synthase in OS, for example during hypoxia, granting photoreceptor survival. PMID:23568658

Calzia, Daniela; Candiani, Simona; Garbarino, Greta; Caicci, Federico; Ravera, Silvia; Bruschi, Maurizio; Manni, Lucia; Morelli, Alessandro; Traverso, Carlo Enrico; Candiano, Giovanni; Tacchetti, Carlo; Panfoli, Isabella

2013-04-09

160

Life without definitions  

Microsoft Academic Search

The question ‘what is life?’ has long been a source of philosophical debate and in recent years has taken on increasing scientific\\u000a importance. The most popular approach among both philosophers and scientists for answering this question is to provide a “definition”\\u000a of life. In this article I explore a variety of different definitional approaches, both traditional and non-traditional, that\\u000a have

Carol E. Cleland

161

Snapshots of the maltose transporter during ATP hydrolysis  

SciTech Connect

ATP-binding cassette transporters are powered by ATP, but the mechanism by which these transporters hydrolyze ATP is unclear. In this study, four crystal structures of the full-length wild-type maltose transporter, stabilized by adenosine 5{prime}-({beta},{gamma}-imido)triphosphate or ADP in conjunction with phosphate analogs BeF{sub 3}{sup -}, VO{sub 4}{sup 3-}, or AlF{sub 4}{sup -}, were determined to 2.2- to 2.4-{angstrom} resolution. These structures led to the assignment of two enzymatic states during ATP hydrolysis and demonstrate specific functional roles of highly conserved residues in the nucleotide-binding domain, suggesting that ATP-binding cassette transporters catalyze ATP hydrolysis via a general base mechanism.

Oldham, Michael L.; Chen, Jue (Purdue)

2011-12-05

162

Luminometric single step urea assay using ATP-hydrolyzing urease  

Microsoft Academic Search

An automatic enzyme kinetic luminometric method for determination of small quantities of urea in biological fluids and in microdialysates is presented. The method is based on the ATP-hydrolyzing urease reaction (urea amidohydrolase (ATP-hydrolyzing); EC 3.5.1.45), moni- tored by a luciferin-luciferase ATP reaction. The assay range is 100 pmol to 50 nmol with a detection limit of 5 mmol\\/L in the

Birgitta Naslund; Lars Stahle; Arne Lundin; Bjorn Anderstam; Peter Arner; Jonas Bergstrom

163

ATP7B detoxifies silver in ciliated airway epithelial cells  

SciTech Connect

Silver is a centuries-old antibiotic agent currently used to treat infected burns. The sensitivity of a wide range of drug-resistant microorganisms to silver killing suggests that it may be useful for treating refractory lung infections. Toward this goal, we previously developed a methylated caffeine silver acetate compound, SCC1, that exhibits broad-spectrum antimicrobial activity against clinical strains of bacteria in vitro and when nebulized to lungs in mouse infection models. Preclinical testing of high concentrations of SCC1 in primary culture mouse tracheal epithelial cells (mTEC) showed selective ciliated cell death. Ciliated cell death was induced by both silver- and copper-containing compounds but not by the methylated caffeine portion of SCC1. We hypothesized that copper transporting P-type ATPases, ATP7A and ATP7B, play a role in silver detoxification in the airway. In mTEC, ATP7A was expressed in non-ciliated cells, whereas ATP7B was expressed only in ciliated cells. The exposure of mTEC to SCC1 induced the trafficking of ATP7B, but not ATP7A, suggesting the presence of a cell-specific silver uptake and detoxification mechanisms. Indeed, the expression of the copper uptake protein CTR1 was also restricted to ciliated cells. A role of ATP7B in silver detoxification was further substantiated when treatment of SCC1 significantly increased cell death in ATP7B shRNA-treated HepG2 cells. In addition, mTEC from ATP7B{sup -/-} mice showed enhanced loss of ciliated cells compared to wild type. These studies are the first to demonstrate a cell type-specific expression of the Ag{sup +}/Cu{sup +} transporters ATP7A, ATP7B, and CTR1 in airway epithelial cells and a role for ATP7B in detoxification of these metals in the lung.

Ibricevic, Aida, E-mail: aidaibricevic@hotmail.co [Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States); Brody, Steven L., E-mail: sbrody@dom.wustl.ed [Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States); Youngs, Wiley J., E-mail: youngs@uakron.ed [Department of Chemistry, University of Akron, Akron, OH 44325 (United States); Cannon, Carolyn L., E-mail: carolyn.cannon@utsouthwestern.ed [Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110 (United States)

2010-03-15

164

Synaptic Co-Release of ATP and GABA  

Microsoft Academic Search

\\u000a Over the last 30 years, adenosine 5’-triphosphate (ATP) has been clearly established as a cotransmitter with noradrenaline\\u000a and acetylcholine in the peripheral nervous system. More recently, ATP was also identified as a cotransmitter in the central\\u000a nervous system. In neuronal cultures from postnatal rat spinal cord dorsal horn or embryonic chick and postnatal mouse lateral\\u000a hypothalamus, ATP was surprisingly found

S. Hugel; Y. H. Jo; R. Schlichter

165

Therapeutic Targeting of ATP7B in Ovarian Carcinoma  

PubMed Central

Purpose Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. Experimental Design Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). Results ATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC50 levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH2-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis. Conclusion These data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance.

Mangala, Lingegowda S.; Zuzel, Vesna; Schmandt, Rosemarie; Leshane, Erik S.; Halder, Jyotsna B.; Armaiz-Pena, Guillermo N.; Spannuth, Whitney A.; Tanaka, Takemi; Shahzad, Mian M.K.; Lin, Yvonne G.; Nick, Alpa M.; Danes, Christopher G.; Lee, Jeong-Won; Jennings, Nicholas B.; Vivas-Mejia, Pablo E.; Wolf, Judith K.; Coleman, Robert L.; Siddik, Zahid H.; Lopez-Berestein, Gabriel; Lutsenko, Svetlana; Sood, Anil K.

2009-01-01

166

From ATP to Timed Graphs and Hybrid Systems  

Microsoft Academic Search

The paper presents results of ongoing work aiming at the unification of some behavioraldescription formalisms for timed systems.We propose for the algebra of timed processes ATP a very general semantics in terms ofa time domain.It is then shown how ATP can be translated into a variant of timed graphs. This resultallows the application of existing model-checking techniques to ATP.Finally, we

Xavier Nicollin; Joseph Sifakis; Sergio Yovine

1993-01-01

167

ATP7B detoxifies silver in ciliated airway epithelial cells  

PubMed Central

Silver is a centuries old antibiotic agent currently used to treat infected burns. The sensitivity of a wide range of drug-resistant microorganisms to silver killing suggests that it may be useful for treating refractory lung infections. Toward this goal, we previously developed a methylated caffeine silver acetate compound, SCC1, that exhibits broad-spectrum antimicrobial activity against clinical strains of bacteria in vitro and when nebulized to lungs in mouse infection models. Preclinical testing of high concentrations of SCC1 in primary culture mouse tracheal epithelial cells (mTEC) showed selective ciliated cell death. Ciliated cell death was induced by both silver- and copper-containing compounds, but not by the methylated caffeine portion of SCC1. We hypothesized that copper transporting P-type ATPases, ATP7A and ATP7B, play a role in silver detoxification in the airway. In mTEC, ATP7A was expressed in non-ciliated cells, whereas ATP7B was expressed only in ciliated cells. The exposure of mTEC to SCC1 induced the trafficking of ATP7B, but not ATP7A, suggesting the presence of a cell-specific silver uptake and detoxification mechanisms. Indeed, the expression of the copper uptake protein CTR1 was also restricted to ciliated cells. A role of ATP7B in silver detoxification was further substantiated when treatment of SCC1 significantly increased cell death in ATP7B shRNA treated HepG2 cells. Additionally, mTEC from ATP7B-/- mice showed enhanced loss of ciliated cells compared to wild type. These studies are the first to demonstrate a cell-type specific expression of the Ag+/Cu+ transporters ATP7A, ATP7B and CTR1 in airway epithelial cells, and a role for ATP7B in detoxification of these metals in the lung.

Ibricevic, Aida; Brody, Steven L.; Youngs, Wiley J.; Cannon, Carolyn L.

2010-01-01

168

ATP7A gene addition to the choroid plexus results in long-term rescue of the lethal copper transport defect in a Menkes disease mouse model.  

PubMed

Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous copper injections) is not entirely effective in the majority of affected individuals. The mottled-brindled (mo-br) mouse recapitulates the Menkes phenotype, including abnormal copper transport to the brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age. We documented that mo-br mice on C57BL/6 background were not rescued by peripheral copper administration, and used this model to evaluate brain-directed therapies. Neonatal mo-br mice received lateral ventricle injections of either adeno-associated virus serotype 5 (AAV5) harboring a reduced-size human ATP7A (rsATP7A) complementary DNA (cDNA), copper chloride, or both. AAV5-rsATP7A showed selective transduction of choroid plexus epithelia and AAV5-rsATP7A plus copper combination treatment rescued mo-br mice; 86% survived to weaning (21 days), median survival increased to 43 days, 37% lived beyond 100 days, and 22% survived to the study end point (300 days). This synergistic treatment effect correlated with increased brain copper levels, enhanced activity of dopamine-?-hydroxylase, a copper-dependent enzyme, and correction of brain pathology. Our findings provide the first definitive evidence that gene therapy may have clinical utility in the treatment of Menkes disease. PMID:21878905

Donsante, Anthony; Yi, Ling; Zerfas, Patricia M; Brinster, Lauren R; Sullivan, Patricia; Goldstein, David S; Prohaska, Joseph; Centeno, Jose A; Rushing, Elisabeth; Kaler, Stephen G

2011-08-30

169

ATP-independent contractile proteins from plants  

NASA Astrophysics Data System (ADS)

Emerging technologies are creating increasing interest in smart materials that may serve as actuators in micro- and nanodevices. Mechanically active polymers currently studied include a variety of materials. ATP-driven motor proteins, the actuators of living cells, possess promising characteristics, but their dependence on strictly defined chemical environments can be disadvantagous. Natural proteins that deform reversibly by entropic mechanisms might serve as models for artificial contractile polypeptides with useful functionality, but they are rare. Protein bodies from sieve elements of higher plants provide a novel example. sieve elements form microfluidics systems for pressure-driven transport of photo-assimilates throughout the plant. Unique protein bodies in the sieve elements of legumes act as cellular stopcocks, by undergoing a Ca2+-dependent conformational switch in which they plug the sieve element. In living cells, this reaction is probably controlled by Ca2+-transporters in the cell membrane. Here we report the rapid, reversible, anisotropic and ATP-independent contractility in these protein bodies in vitro. Considering the unique biological function of the legume 'crystalloid' protein bodies and their contractile properties, we suggest to give them the distinctive name forisome ('gate-body'; from the Latin foris, the wing of a gate).

Knoblauch, Michael; Noll, Gundula A.; Müller, Torsten; Prüfer, Dirk; Schneider-Hüther, Ingrid; Scharner, Dörte; van Bel, Aart J. E.; Peters, Winfried S.

2003-09-01

170

Release kinetics of ATP in cells exposed to nonionic detergents.  

PubMed

We have previously shown that the protein binding of intracellular ATP could be examined by monitoring the ATP release kinetics from Triton X-100 and Brij 58 nonionic detergent permeabilized cells. We have now analysed the protein binding of ATP in an isotonic medium using intact and partially ATP depleted Brij 58 treated human erythrocytes. The effects of Triton X-100 below the critical micelle concentration (CMC) was studied in normal and tumorous tissue culture cells and human red blood cells. Our results showed that the protein association of ATP was altered in the partially ATP depleted erythrocytes. Below the CMC value, but above a critical level Triton X-100 treatment was effective in mobilizing the intracellular ATP in both cell types. The ATP release curves were sigmoidal and an 'all or none' type of response was observed, especially in erythrocytes. The use of Triton X-100 (less than CMC) delays the detergent-induced cell decomposition time thus providing a new approach to investigating the physical state of intracellular ATP. PMID:1746315

Köszegi, T

171

Lanthanide(III) complexes of bis-semicarbazone and bis-imine-substituted phenanthroline ligands: solid-state structures, photophysical properties, and anion sensing.  

PubMed

Phenanthroline-based hexadentate ligands L(1) and L(2) bearing two achiral semicarbazone or two chiral imine moieties as well as the respective mononuclear complexes incorporating various lanthanide ions, such as La(III), Eu(III), Tb(III), Lu(III), and Y(III) metal ions, were synthesized, and the crystal structures of [ML(1)Cl(3)] (M=La(III), Eu(III), Tb(III), Lu(III), or Y(III)) complexes were determined. Solvent or water molecules act as coligands for the rare-earth metals in addition to halide anions. The big Ln(III) ion exhibits a coordination number (CN) of 10, whereas the corresponding Eu(III), Tb(III), Lu(III), and Y(III) centers with smaller ionic radii show CN=9. Complexes of L(2), namely [ML(2)Cl(3)] (M=Eu(III), Tb(III), Lu(III), or Y(III)) ions could also be prepared. Only the complex of Eu(III) showed red luminescence, whereas all the others were nonluminescent. The emission properties of the Eu derivative can be applied as a photophysical signal for sensing various anions. The addition of phosphate anions leads to a unique change in the luminescence behavior. As a case study, the quenching behavior of adenosine-5'-triphosphate (ATP) was investigated at physiological pH value in an aqueous solvent. A specificity of the sensor for ATP relative to adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) was found. (31)P NMR spectroscopic studies revealed the formation of a [EuL(2)(ATP)] coordination species. PMID:23150237

Nadella, Sandeep; Selvakumar, Paulraj M; Suresh, Eringathodi; Subramanian, Palani S; Albrecht, Markus; Giese, Michael; Fröhlich, Roland

2012-11-13

172

Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5)P2  

PubMed Central

Transient receptor potential vanilloid 6 (TRPV6) channels play an important role in Ca2+ absorption in the intestines. Both phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] and cytoplasmic ATP have been proposed to be important for maintaining TRPV6 activity. To evaluate whether PtdIns(4,5)P2 and ATP affect channel activity directly or indirectly, we have used a dual approach, examining channel activity in excised patches and planar lipid bilayers. In excised inside-out patch-clamp measurements, ATP reactivated the human TRPV6 channels after current rundown only in the presence of Mg2+. The effect of MgATP was inhibited by 3 structurally different compounds that inhibit type III phosphatidylinositol 4-kinases (PI4Ks). PtdIns(4,5)P2 also activated TRPV6 in excised patches, while its precursor PtdIns(4)P had only minimal effect. These data demonstrate that MgATP provides substrate for lipid kinases, allowing the resynthesis of PtdIns(4,5)P2. To determine whether PtdIns(4,5)P2 is a direct activator of TRPV6, we purified and reconstituted the channel protein in planar lipid bilayers. The reconstituted channel showed high activity in the presence of PtdIns(4,5)P2, while PtdIns(4)P induced only minimal activity. Our data establish PtdIns(4,5)P2 as a direct activator of TRPV6 and demonstrate that intracellular ATP regulates the channel indirectly as a substrate for type III PI4Ks.—Zakharian, E., Cao, C., Rohacs, T. Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5)P2.

Zakharian, Eleonora; Cao, Chike; Rohacs, Tibor

2011-01-01

173

Calcium Regulation of Tension Redevelopment Kinetics with 2-Deoxy-ATP or Low [ATP] in Rabbit Skeletal Muscle  

Microsoft Academic Search

The correlation of acto-myosin ATPase rate with tension redevelopment kinetics (ktr) was determined during Ca+2-activated contractions of demembranated rabbit psoas muscle fibers; the ATPase rate was either increased or decreased relative to control by substitution of ATP (5.0mM) with 2-deoxy-ATP (dATP) (5.0mM) or by lowering [ATP] to 0.5mM, respectively. The activation dependence of ktr and unloaded shortening velocity (Vu) was

M. Regnier; D. A. Martyn; P. B. Chase

1998-01-01

174

Testing atypical depression definitions.  

PubMed

The evidence supporting the DSM-IV definition of atypical depression (AD) is weak. This study aimed to test different definitions of AD. Major depressive disorder (MDD) patients (N = 254) and bipolar-II (BP-II) outpatients (N = 348) were interviewed consecutively, during major depressive episodes, with the Structured Clinical Interview for DSM-IV. DSM-IV criteria for AD were followed. AD validators were female gender, young onset, BP-II, axis I comorbidity, bipolar family history. Frequency of DSM-IV AD was 43.0%. AD, versus non-AD, was significantly associated with all AD validators, apart from comorbidity when controlling for age and sex. Factor analysis of atypical symptoms found factor 1 including oversleeping, overeating and weight gain (leaden paralysis at trend correlation), and factor 2 including interpersonal sensitivity, mood reactivity, and leaden paralysis. Multiple logistic regression of factor 1 versus AD validators found significant associations with several validators (including bipolar family history), whereas factor 2 had no significant associations. Findings may support a new definition of AD based on the state-dependent features oversleeping and overeating (plus perhaps leaden paralysis) versus the current AD definition based on a combination of state and trait features. Pharmacological studies are required to support any new definition of AD, as the current concept of AD is based on different response to TCA antidepressants versus non-AD. PMID:16175877

Benazzi, Franco

2005-01-01

175

Ecotourism: The Evolving Contemporary Definition  

Microsoft Academic Search

A rise in the popularity of ecotourism has coincided with voluminous definitional discourse. Amongst stakeholders, confusion has resulted from the disparate nature of these definitions. In the absence of a common definition or set of key tenets the challenge has been to ensure operational ecotourism that adheres to the theoretical underpinnings of the concept. Without some semblance of definitional consensus,

Holly M. Donohoe; Roger D. Needham

2006-01-01

176

Statute Definitions of Elder Abuse  

Microsoft Academic Search

Differences in elder abuse definitions hinder the comparison of research and state elder abuse data (Jogerst, Daly, Brinig et al., in press). The purposes of this paper are to describe and summarize the elder abuse definitions in the state statutes and present current definitions used in practice, education, and research. The definitions of elder abuse for the 50 state and

Jeanette M. Daly; Gerald Jogerst

2003-01-01

177

Structured Analysis for Requirements Definition  

Microsoft Academic Search

Requirements definition encompasses all aspects of system development prior to actual system design. We see the lack of an adequate approach to requirements definition as the source of major difficulties in current systems worlk This paper examines the needs for requirements definition, and proposes meeting those objectives with three interrelated subjects: context analysis, functional specification, and design constraints. Requirements definition

Douglas T. Ross; Kenneth E. Schoman Jr.

1977-01-01

178

ATP storage and uptake by isolated pancreatic zymogen granules.  

PubMed

ATP is released from pancreatic acini in response to cholinergic and hormonal stimulation. The same stimuli cause exocytosis of ZG (zymogen granules) and release of digestive enzymes. The aim of the present study was to determine whether ZG stored ATP and to characterize the uptake mechanism for ATP transport into the ZG. ZG were isolated and the ATP content was measured using luciferin/luciferase assays and was related to protein in the sample. The estimate of ATP concentration in freshly isolated granules was 40-120 microM. The ATP uptake had an apparent Km value of 4.9+/-2.1 mM when granules were incubated without Mg2+ and a Km value of 0.47+/-0.05 mM in the presence of Mg2+, both in pH 6.0 buffers. The uptake of ATP was significantly higher at pH 7.2 compared with pH 6.0 solutions. The anion transport blockers DIDS (4,4'-di-isothiocyanostilbene-2,2'-disulfonate) and Evans Blue inhibited ATP transport. Western blot analysis on the ZG showed the presence of VNUT (vesicular nucleotide transporter). Together, these findings indicate that VNUT may be responsible for the ATP uptake into ZG. Furthermore, the present study shows the presence of ATP together with digestive enzymes in ZG. This indicates that co-released ATP would regulate P2 receptors in pancreatic ducts and, thus, ductal secretion, and this would aid delivery of enzymes to the duodenum. PMID:20441565

Haanes, Kristian A; Novak, Ivana

2010-07-15

179

ATP-driven molecular chaperone machines.  

PubMed

This review is focused on the mechanisms by which ATP binding and hydrolysis drive chaperone machines assisting protein folding and unfolding. A survey of the key, general chaperone systems Hsp70 and Hsp90, and the unfoldase Hsp100 is followed by a focus on the Hsp60 chaperonin machine which is understood in most detail. Cryo-electron microscopy analysis of the E. coli Hsp60 GroEL reveals intermediate conformations in the ATPase cycle and in substrate folding. These structures suggest a mechanism by which GroEL can forcefully unfold and then encapsulate substrates for subsequent folding in isolation from all other binding surfaces. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 846-859, 2013. PMID:23877967

Clare, Daniel K; Saibil, Helen R

2013-11-01

180

Substantia nigra osmoregulation: taurine and ATP involvement.  

PubMed

An extracellular nonsynaptic taurine pool of glial origin was recently reported in the substantia nigra (SN). There is previous evidence showing taurine as an inhibitory neurotransmitter in the SN, but the physiological role of this nonsynaptic pool of taurine has not been explored. By using microdialysis methods, we studied the action of local osmolarity on the nonsynaptic taurine pool in the SN of the rat. Hypoosmolar pulses (285-80 mosM) administered in the SN by the microdialysis probe increased extrasynaptic taurine in a dose-dependent way, a response that was counteracted by compensating osmolarity with choline. The opposite effect (taurine decrease) was observed when osmolarity was increased. Under basal conditions, the blockade of either the AMPA-kainate glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dionine disodium or the purinergic receptors with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid modified the taurine concentration, suggesting that both receptors modulate the extrasynaptic pool of taurine. In addition, these drugs decreased the taurine response to hypoosmolar pulses, suggesting roles for glutamatergic and purinergic receptors in the taurine response to osmolarity. The participation of purinergic receptors was also supported by the fact that ATP (which, under basal conditions, increased the extrasynaptic taurine in a dose-dependent way) administered in doses saturating purinergic receptors also decreased the taurine response to hypoosmolarity. Taken together, present data suggest osmoregulation as a role of the nonsynaptic taurine pool of the SN, a function that also involves glutamate and ATP and that could influence the nigral cell vulnerability in Parkinson's disease. PMID:17215320

Morales, Ingrid; Dopico, Jose G; Sabate, Magdalena; Gonzalez-Hernandez, Tomas; Rodriguez, Manuel

2007-01-10

181

DEFINITION FOR ASBESTOS.  

USGS Publications Warehouse

A definition of asbestos is proposed. Under this definition, the term asbestos applies to six naturally occurring minerals exploited commercially for their desirable physical properties, which are in part derived from their asbestiform habit. The six minerals are the serpentine mineral chrysotile and the amphibole minerals grunerite asbestos (also referred to as amosite), riebeckite asbestos (also referred to as crocidolite), anthophyllite asbestos, tremolite asbestos, and actinolite asbestos. Individual mineral particles, however processed and regardless of their mineral name, are not demonstrated to be asbestos if the length-to-width ratio is less than 20:1.

Ross, Malcolm; Kuntze, Richard, A.; Clifton, Robert, A.

1984-01-01

182

Enzymatic synthesis of PAPS with an ATP-regeneration system.  

PubMed

Sulfate activating enzymes, ATP sulfurylase and APS kinase, were newly isolated from a thermophile, Bacillus stearothermophilus. Adenosine 3'-phosphate 5'-phosphosulfate (PAPS) was synthesized by these enzymes. The reaction proceeded more efficiently when an ATP-regeneration system, using acetate kinase, was coupled to the reaction system. PMID:1337784

Ibuki, H; Tashiro, T; Hayashi, M; Nakajima, H; Liu, M C; Suiko, M

1992-01-01

183

Increased resistance of glioma cell lines to extracellular ATP cytotoxicity  

Microsoft Academic Search

Glioblastomas are the most common form of primary tumors of the central nervous system (CNS) and despite treatment, patients with these tumors have a very poor prognosis. ATP and other nucleotides and nucleosides are very important signaling molecule in physiological and pathological conditions in the CNS. ATP is degraded very slowly by gliomas when compared to astrocytes, potentially resulting in

Fernanda B. Morrone; Ana Paula Horn; Joseli Stella; Fernando Spiller; João J. F. Sarkis; Christianne G. Salbego; Guido Lenz; Ana Maria O. Battastini

2005-01-01

184

Mechanically driven ATP synthesis by F1-ATPase  

NASA Astrophysics Data System (ADS)

ATP, the main biological energy currency, is synthesized from ADP and inorganic phosphate by ATP synthase in an energy-requiring reaction. The F1 portion of ATP synthase, also known as F1-ATPase, functions as a rotary molecular motor: in vitro its ?-subunit rotates against the surrounding ?3?3 subunits, hydrolysing ATP in three separate catalytic sites on the ?-subunits. It is widely believed that reverse rotation of the ?-subunit, driven by proton flow through the associated Fo portion of ATP synthase, leads to ATP synthesis in biological systems. Here we present direct evidence for the chemical synthesis of ATP driven by mechanical energy. We attached a magnetic bead to the ?-subunit of isolated F1 on a glass surface, and rotated the bead using electrical magnets. Rotation in the appropriate direction resulted in the appearance of ATP in the medium as detected by the luciferase-luciferin reaction. This shows that a vectorial force (torque) working at one particular point on a protein machine can influence a chemical reaction occurring in physically remote catalytic sites, driving the reaction far from equilibrium.

Itoh, Hiroyasu; Takahashi, Akira; Adachi, Kengo; Noji, Hiroyuki; Yasuda, Ryohei; Yoshida, Masasuke; Kinosita, Kazuhiko

2004-01-01

185

Electrophysiological Effects of Extracellular ATP on Necturus Epithelium Gallbladder  

Microsoft Academic Search

The effects of addition of ATP to the mucosal bathing solution on transepithelial, apical, and basolateral membrane voltages and resistances in Nectu- rus gallbladder epithelium were determined. Mucosal ATP (100 IxM) caused a rapid hyperpolarization of both apical (Vmc) and basolateral (Vcs) cell membrane voltages (AV m -- 18 -+ 1 mV), a fall in transepithelial resistance (Rt) from 142

CALVIN U. COTTON

186

Renal epithelial cells can release ATP by vesicular fusion  

PubMed Central

Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30), which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1) cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin) reduced both the spontaneous and hypotonically (80%)-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1) and vesicular transport (nocodazole). These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ~90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP) or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50%) or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8 and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells.

Bjaelde, Randi G.; Arnadottir, Sigrid S.; Overgaard, Morten T.; Leipziger, Jens; Praetorius, Helle A.

2013-01-01

187

The ATP synthase: the understood, the uncertain and the unknown.  

PubMed

The ATP synthases are multiprotein complexes found in the energy-transducing membranes of bacteria, chloroplasts and mitochondria. They employ a transmembrane protonmotive force, ?p, as a source of energy to drive a mechanical rotary mechanism that leads to the chemical synthesis of ATP from ADP and Pi. Their overall architecture, organization and mechanistic principles are mostly well established, but other features are less well understood. For example, ATP synthases from bacteria, mitochondria and chloroplasts differ in the mechanisms of regulation of their activity, and the molecular bases of these different mechanisms and their physiological roles are only just beginning to emerge. Another crucial feature lacking a molecular description is how rotation driven by ?p is generated, and how rotation transmits energy into the catalytic sites of the enzyme to produce the stepping action during rotation. One surprising and incompletely explained deduction based on the symmetries of c-rings in the rotor of the enzyme is that the amount of energy required by the ATP synthase to make an ATP molecule does not have a universal value. ATP synthases from multicellular organisms require the least energy, whereas the energy required to make an ATP molecule in unicellular organisms and chloroplasts is higher, and a range of values has been calculated. Finally, evidence is growing for other roles of ATP synthases in the inner membranes of mitochondria. Here the enzymes form supermolecular complexes, possibly with specific lipids, and these complexes probably contribute to, or even determine, the formation of the cristae. PMID:23356252

Walker, John E

2013-02-01

188

Astrocyte-derived ATP modulates depressive-like behaviors.  

PubMed

Major depressive disorder (MDD) is a cause of disability that affects approximately 16% of the world's population; however, little is known regarding the underlying biology of this disorder. Animal studies, postmortem brain analyses and imaging studies of patients with depression have implicated glial dysfunction in MDD pathophysiology. However, the molecular mechanisms through which astrocytes modulate depressive behaviors are largely uncharacterized. Here, we identified ATP as a key factor involved in astrocytic modulation of depressive-like behavior in adult mice. We observed low ATP abundance in the brains of mice that were susceptible to chronic social defeat. Furthermore, we found that the administration of ATP induced a rapid antidepressant-like effect in these mice. Both a lack of inositol 1,4,5-trisphosphate receptor type 2 and transgenic blockage of vesicular gliotransmission induced deficiencies in astrocytic ATP release, causing depressive-like behaviors that could be rescued via the administration of ATP. Using transgenic mice that express a Gq G protein-coupled receptor only in astrocytes to enable selective activation of astrocytic Ca(2+) signaling, we found that stimulating endogenous ATP release from astrocytes induced antidepressant-like effects in mouse models of depression. Moreover, we found that P2X2 receptors in the medial prefrontal cortex mediated the antidepressant-like effects of ATP. These results highlight astrocytic ATP release as a biological mechanism of MDD. PMID:23644515

Cao, Xiong; Li, Liang-Ping; Wang, Qian; Wu, Qiong; Hu, Hong-Hai; Zhang, Meng; Fang, Ying-Ying; Zhang, Jie; Li, Shu-Ji; Xiong, Wen-Chao; Yan, Hua-Cheng; Gao, Yu-Bo; Liu, Ji-Hong; Li, Xiao-Wen; Sun, Li-Rong; Zeng, Yuan-Ning; Zhu, Xin-Hong; Gao, Tian-Ming

2013-05-05

189

Phosphate and R2D2 Restrict the Substrate Specificity of Dicer-2, an ATP-Driven Ribonuclease  

PubMed Central

SUMMARY Drosophila Dicer-2 generates small interfering RNAs (siRNAs) from long double-stranded RNA (dsRNA), whereas Dicer-1 produces microRNAs from pre-microRNA. What makes the two Dicers specific for their biological substrates? We find that purified Dicer-2 can efficiently cleave pre-miRNA, but that inorganic phosphate and the Dicer-2 partner protein R2D2 inhibit pre-miRNA cleavage. Dicer-2 contains C-terminal RNase III domains that mediate RNA cleavage, and an N-terminal helicase motif whose function is unclear. We show that Dicer-2 is a dsRNA-stimulated ATPase that hydrolyzes ATP to ADP; ATP hydrolysis is required for Dicer-2 to process long dsRNA, but not pre-miRNA. Wild-type Dicer-2, but not a mutant defective in ATP hydrolysis, can generate siRNAs faster than it can dissociate from a long dsRNA substrate. We propose that the Dicer-2 helicase domain uses ATP to generate many siRNAs from a single molecule of dsRNA before dissociating from its substrate.

Cenik, Elif Sarinay; Fukunaga, Ryuya; Lu, Gang; Dutcher, Robert; Wang, Yeming; Tanaka Hall, Traci M.; Zamore, Phillip D.

2011-01-01

190

In Vivo Function of Hsp90 Is Dependent on ATP Binding and ATP Hydrolysis  

Microsoft Academic Search

Heat shock protein 90 (Hsp90), an abundant molecular chaperone in the eukaryotic cytosol, is in- volved in the folding of a set of cell regulatory proteins and in the re-folding of stress-denatured polypeptides. The basic mechanism of action of Hsp90 is not yet un- derstood. In particular, it has been debated whether Hsp90 function is ATP dependent. A recent crystal

Wolfgang M. J. Obermann; Holger Sondermann; Alicia A. Russo; Nikola P. Pavletich; F. Ulrich Hartl

1998-01-01

191

Sodium ion translocation and ATP synthesis in methanogens.  

PubMed

Methanogens are the only significant biological producers of methane. A limited number of C(1) substrates, such as methanol, methylamines, methyl sulfate, formate, H(2)+CO(2) or CO, and acetate, serve as carbon and energy source. During degradation of these compounds, a primary proton as well as a primary sodium ion gradient is established, which is a unique feature of methanogens. This raises the question about the coupling ion for ATP synthesis by the unique A(1)A(o) ATP synthase. Here, we describe how to analyze and determine the Na(+) dependence of two model methanogens, the hydrogenotrophic Methanothermobacter thermautotrophicus and the methylotrophic Methanosarcina barkeri. Furthermore, the determination of important bioenergetic parameters like the ?pH, ??, or the intracellular volume in M. barkeri is described. For the analyses of the A(1)A(O) ATP synthase, methods for measurement of ATP synthesis as well as ATP hydrolysis in Methanosarcina mazei Gö1 are described. PMID:21402218

Schlegel, Katharina; Müller, Volker

2011-01-01

192

Radioprotective effects of ATP in human blood ex vivo  

SciTech Connect

Damage to healthy tissue is a major limitation of radiotherapy treatment of cancer patients, leading to several side effects and complications. Radiation-induced release of pro-inflammatory cytokines is thought to be partially responsible for the radiation-associated complications. The aim of the present study was to investigate the protective effects of extracellular ATP on markers of oxidative stress, radiation-induced inflammation and DNA damage in irradiated blood ex vivo. ATP inhibited radiation-induced TNF-{alpha} release and increased IL-10 release. The inhibitory effect of ATP on TNF- {alpha} release was completely reversed by adenosine 5'-O-thiomonophosphate, indicating a P2Y{sub 11} mediated effect. Furthermore, ATP attenuated radiation-induced DNA damage immediate, 3 and 6 h after irradiation. Our study indicates that ATP administration alleviates radiation-toxicity to blood cells, mainly by inhibiting radiation-induced inflammation and DNA damage.

Swennen, Els L.R. [Department of Epidemiology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht (Netherlands); Department of Pharmacology and Toxicology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht (Netherlands)], E-mail: e.swennen@farmaco.unimaas.nl; Dagnelie, Pieter C. [Department of Epidemiology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht (Netherlands); Van den Beucken, Twan [Department of Radiation Oncology, Maastricht Radiation oncology (Maastro) Lab, GROW, Maastricht University, P.O. Box 616, 6200 MD Maastricht (Netherlands); Bast, Aalt [Department of Pharmacology and Toxicology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht (Netherlands)

2008-03-07

193

Involvement of connexin43 hemichannel in ATP release after ?-irradiation  

PubMed Central

Ionizing radiation induces biological effects not only in irradiated cells but also in non-irradiated cells, which is called the bystander effect. Recently, in vivo and in vitro experiments have suggested that both gap junction hemichannel connexin43 (Cx43) and extracellular adenosine triphosphate (ATP) released from cells play a role in the bystander effect. We have reported that ?-irradiation induces ATP release from B16 melanoma cells, which is dependent on the P2X7 receptor. However, the mechanism of ATP release caused by irradiation remains unclear. We here show the involvement of Cx43 in P2X7 receptor-dependent ATP release after 0.5 Gy ?-irradiation. Inhibitors of gap junction hemichannels and an inhibitory peptide for Cx43 (gap26), but not an inhibitory peptide for pannexin1 (Panx1), significantly blocked ?-irradiation-induced ATP release from B16 melanoma cells. We confirmed high expression of Cx43 mRNA in B16 melanoma cells. These results suggest involvement of Cx43 in radiation-induced ATP release. We found that after 0.5 Gy ?-irradiation tyrosine phosphorylation was significantly blocked by P2X7 receptor antagonist, but not gap26, suggesting that tyrosine phosphorylation is a downstream event from the P2X7 receptor. Since tyrosine kinase inhibitor significantly suppressed radiation-induced ATP release, tyrosine phosphorylation appears to play an important role in the Cx43-mediated ATP release downstream of the P2X7 receptor. In conclusion, the Cx43 hemichannel, which lies downstream of the P2X7 receptor, is involved in ATP release in response to radiation. Our results suggest a novel mechanism for radiation-induced biological effects mediated by both ATP and Cx43.

Ohshima, Yasuhiro; Tsukimoto, Mitsutoshi; Harada, Hitoshi; Kojima, Shuji

2012-01-01

194

Local Warning System Definition.  

National Technical Information Service (NTIS)

The document is the final report of the Local Warning System Definition project. The report describes a method for determining an optimum mixture of public warning systems. Two types of input data to the optimum mixture method are developed: warning effec...

B. D. Miller

1970-01-01

195

Definition and Measurement  

Microsoft Academic Search

0 Abstract Among the several notions and expressions used in urban morphological description and analysis, complexity is a very common one. Nevertheless it has been used in a quite loose and fuzzy way, never getting enough definition and precision. In this sense, the expression, instead of clarifying descriptions, helps to actually blur them. This paper reports an attempt to give

Romûlo Krafta; Sul Rua; Sarmento Leite; Porto Alegre

196

Center of buoyancy definition  

SciTech Connect

The center of buoyancy of an arbitrary shaped body is defined in analogy to the center of gravity. The definitions of the buoyant force and center of buoyancy in terms of integrals over the area of the body are converted to volume integrals and shown to have simple intuitive interpretations.

Sandberg, V.

1988-12-01

197

The Definition of Atheism  

Microsoft Academic Search

One of the central elements of the secularist tradition is atheism. Atheism has a long history and is nowadays again heavily debated. This article tries to present a reflection on the nature of atheism. The central thesis is that atheism is often misunderstood. The most fruitful definition of atheism is a negative one: an atheist does not believe in the

Paul Cliteur

2009-01-01

198

[Borderline resectable pancreatic cancer - a definition and effective treatment strategy].  

PubMed

The survival benefit of extended surgery for advanced pancreatic cancer has been denied by four randomized controlled trials. However, there still is confusion and conflict over the definition and effective treatment strategy for so-called locally advanced or borderline resectable pancreatic cancer. Although there are a number of reports that showed outcomes of preoperative chemotherapy or chemoradiotherapy for this disease, the definitions and treatment regimens described in these studies vary. Moreover, all of the studies were Phase I / II trials or retrospective analysis, and there is no Phase III trial currently focused on this issue. It is urgently necessary to establish an international consensus on the definition of borderline resectable pancreatic cancer. The usefulness of neoadjuvant treatment for this disease should also be elucidated in future clinical trials. In this review article, we discuss the current understanding and definition of borderline resectable pancreatic cancer, and the value of neoadjuvant treatment strategy for treating it. PMID:22421757

Yokoyama, Yukihiro; Ebata, Tomoki; Igami, Tsuyoshi; Sugawara, Gen; Takahashi, Yuh; Kokuryo, Toshio; Tsunoda, Nobuyuki; Fukaya, Masahide; Uehara, Keisuke; Itatsu, Keita; Yoshioka, Yuichiro; Nagino, Masato

2012-03-01

199

15 CFR 295.11 - Technical and educational services for ATP recipients.  

Code of Federal Regulations, 2013 CFR

... Technical and educational services for ATP recipients. 295.11 Section 295... Technical and educational services for ATP recipients. (a) Under the...Technology. (c) From time to time, ATP may conduct public workshops and...

2013-01-01

200

15 CFR 295.11 - Technical and educational services for ATP recipients.  

Code of Federal Regulations, 2010 CFR

... Technical and educational services for ATP recipients. 295.11 Section 295... Technical and educational services for ATP recipients. (a) Under the...Technology. (c) From time to time, ATP may conduct public workshops and...

2010-01-01

201

15 CFR 295.11 - Technical and educational services for ATP recipients.  

Code of Federal Regulations, 2012 CFR

... Technical and educational services for ATP recipients. 295.11 Section 295... Technical and educational services for ATP recipients. (a) Under the...Technology. (c) From time to time, ATP may conduct public workshops and...

2012-01-01

202

75 FR 8467 - Airworthiness Directives; BAE SYSTEMS (Operations) Limited Model ATP Airplanes  

Federal Register 2010, 2011, 2012, 2013

...BAE SYSTEMS (Operations) Limited Model ATP Airplanes AGENCY: Federal Aviation Administration...were introduced by Service Bulletin (SB) ATP-51-002 * * *. As it was determined...were introduced by Service Bulletin (SB) ATP-51- 002, which supplemented and in...

2010-02-25

203

15 CFR 295.11 - Technical and educational services for ATP recipients.  

Code of Federal Regulations, 2010 CFR

... Technical and educational services for ATP recipients. 295.11 Section 295... Technical and educational services for ATP recipients. (a) Under the...Technology. (c) From time to time, ATP may conduct public workshops and...

2009-01-01

204

Preparation and configurational analysis of the stereoisomers of /beta/,/gamma/-bidentate Rh(H/sub 2/O)/sub 4/ATP and /alpha/,/beta/,/gamma/-tridentate Rh(H/sub 2/O)/sub 3/ATP. A new class of enzyme active site probes  

SciTech Connect

Exchange-inert Co(III) and Cr(III) complexes of polyphosphates have proved to be useful probes of the structural and biochemical properties of naturally occurring Mg/sup II/(polyphosphate) complexes. However, applications of these complexes are not without limitations. The Cr/sup III/(polyphosphate) probes or their enzymatic products cannot be used in NMR methods because of the paramagnetic nature of the Cr(III) metal. The redox properties of the metal in the Co/sup III/(polyphosphate) complexes require that they also be coordinated to a nitrogen-containing ligand. This requirement is not always convenient. This work reported herein was undertaken to create a new class of exchange-inert metal polyphosphate complexes that contain a metal that is both diamagnetic and redox stable. The preparation, properties, and configurational analysis of the stereoisomers of /beta/, /gamma/-bidentate Rh(H/sub 2/O)/sub 4/ATP (ATP = adenosine 5'-triphosphate) and /alpha/,/beta/,/gamma/-tridentate Rh(H/sub 2/O)/sub 3/ATP are described. 12 refs., 5 figs.

Lu, Z.; Shorter, A.L.; Lin, I.; Dunaway-Mariano, D.

1988-11-16

205

Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue  

PubMed Central

Background ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg) or drug vehicle twice weekly for 8 weeks. Results In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H). High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of distinct subsets of sensory neurons, and could influence the transport and neurotoxicity of oxaliplatin.

2010-01-01

206

Iron(III)-mediated photolysis of outer arm dynein ATPase from sea urchin sperm flagella.  

PubMed

Irradiation of outer arm dynein ATPase from sea urchin sperm tail flagella at 365-410 nm in the presence of Fe(III)-gluconate complex and ATP produces photolytic cleavage at two distinct sites on the beta heavy chain, located approximately 250 and approximately 230 kDa from its amino terminus. The former cut is close to or identical with the V1 site of the vanadate-mediated photocleavage (Gibbons, I.R., Lee-Eiford, A., Mocz, G., Phillipson, C. A., Tang, W.-J.Y., and Gibbons, B.H. (1987) J. Biol. Chem. 262, 2780-2786. The rate of photolysis shows a hyperbolic dependence on Fe(III)-gluconate concentration with half-maximal rate occurring at 23 microM at pH 6.3. In the presence of 0.1-0.5 mM Fe(III)-gluconate-ATP, approximately 58% of the beta chain becomes cleaved with a half-time of about 34 s; the remainder of the beta chain and almost all of the alpha chain are resistant to cleavage. This photolytic cleavage of the beta chain is accompanied by an approximately parallel loss of the dynein latent ATPase activity, whereas the Triton-activated ATPase is lost to a somewhat greater extent. Mg2+ concentrations above approximately 3 mM inhibit photolysis. Substitution of ADP for ATP changes the pattern of cleavage so that both the alpha and beta heavy chain undergo scission but at the 250-kDa site only. AMP, adenyl-5'-yl imidodiphosphate and Fe(II) do not support cleavage at either site. Trivalent rhodium-ATP complexes, as models of MgATP, can also catalyze photolysis of the beta chain at the 250-kDa site. These results suggest that photolysis results from the activation of an Fe(III)-ATP complex bound to the hydrolytic ATP binding site of the beta chain and that both Fe(III) cleavage sites are located close to the nucleotide binding site in the tertiary folding of the beta heavy chain. The cleavage reaction possibly involves initial photoreduction of Fe(III) bound at the Mg2+ binding site in the dynein.Fe.ATP complex, followed by covalent modification of an amino acid side chain that leads to eventual peptide scission. PMID:2137452

Mocz, G; Gibbons, I R

1990-02-15

207

Dimers of mitochondrial ATP synthase form the permeability transition pore.  

PubMed

Here we define the molecular nature of the mitochondrial permeability transition pore (PTP), a key effector of cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds the lateral stalk of the FOF1 ATP synthase. We show that CyPD binds the oligomycin sensitivity-conferring protein subunit of the enzyme at the same site as the ATP synthase inhibitor benzodiazepine 423 (Bz-423), that Bz-423 sensitizes the PTP to Ca(2+) like CyPD itself, and that decreasing oligomycin sensitivity-conferring protein expression by RNAi increases the sensitivity of the PTP to Ca(2+). Purified dimers of the ATP synthase, which did not contain voltage-dependent anion channel or adenine nucleotide translocator, were reconstituted into lipid bilayers. In the presence of Ca(2+), addition of Bz-423 triggered opening of a channel with currents that were typical of the mitochondrial megachannel, which is the PTP electrophysiological equivalent. Channel openings were inhibited by the ATP synthase inhibitor AMP-PNP (?-imino ATP, a nonhydrolyzable ATP analog) and Mg(2+)/ADP. These results indicate that the PTP forms from dimers of the ATP synthase. PMID:23530243

Giorgio, Valentina; von Stockum, Sophia; Antoniel, Manuela; Fabbro, Astrid; Fogolari, Federico; Forte, Michael; Glick, Gary D; Petronilli, Valeria; Zoratti, Mario; Szabó, Ildikó; Lippe, Giovanna; Bernardi, Paolo

2013-03-25

208

Dimers of mitochondrial ATP synthase form the permeability transition pore  

PubMed Central

Here we define the molecular nature of the mitochondrial permeability transition pore (PTP), a key effector of cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds the lateral stalk of the FOF1 ATP synthase. We show that CyPD binds the oligomycin sensitivity-conferring protein subunit of the enzyme at the same site as the ATP synthase inhibitor benzodiazepine 423 (Bz-423), that Bz-423 sensitizes the PTP to Ca2+ like CyPD itself, and that decreasing oligomycin sensitivity-conferring protein expression by RNAi increases the sensitivity of the PTP to Ca2+. Purified dimers of the ATP synthase, which did not contain voltage-dependent anion channel or adenine nucleotide translocator, were reconstituted into lipid bilayers. In the presence of Ca2+, addition of Bz-423 triggered opening of a channel with currents that were typical of the mitochondrial megachannel, which is the PTP electrophysiological equivalent. Channel openings were inhibited by the ATP synthase inhibitor AMP-PNP (?-imino ATP, a nonhydrolyzable ATP analog) and Mg2+/ADP. These results indicate that the PTP forms from dimers of the ATP synthase.

Giorgio, Valentina; von Stockum, Sophia; Antoniel, Manuela; Fabbro, Astrid; Fogolari, Federico; Forte, Michael; Glick, Gary D.; Petronilli, Valeria; Zoratti, Mario; Szabo, Ildiko; Lippe, Giovanna; Bernardi, Paolo

2013-01-01

209

Altered responsiveness to extracellular ATP enhances acetaminophen hepatotoxicity  

PubMed Central

Background Adenosine triphosphate (ATP) is secreted from hepatocytes under physiological conditions and plays an important role in liver biology through the activation of P2 receptors. Conversely, higher extracellular ATP concentrations, as observed during necrosis, trigger inflammatory responses that contribute to the progression of liver injury. Impaired calcium (Ca2+) homeostasis is a hallmark of acetaminophen (APAP)-induced hepatotoxicity, and since ATP induces mobilization of the intracellular Ca2+ stocks, we evaluated if the release of ATP during APAP-induced necrosis could directly contribute to hepatocyte death. Results APAP overdose resulted in liver necrosis, massive neutrophil infiltration and large non-perfused areas, as well as remote lung inflammation. In the liver, these effects were significantly abrogated after ATP metabolism by apyrase or P2X receptors blockage, but none of the treatments prevented remote lung inflammation, suggesting a confined local contribution of purinergic signaling into liver environment. In vitro, APAP administration to primary mouse hepatocytes and also HepG2 cells caused cell death in a dose-dependent manner. Interestingly, exposure of HepG2 cells to APAP elicited significant release of ATP to the supernatant in levels that were high enough to promote direct cytotoxicity to healthy primary hepatocytes or HepG2 cells. In agreement to our in vivo results, apyrase treatment or blockage of P2 receptors reduced APAP cytotoxicity. Likewise, ATP exposure caused significant higher intracellular Ca2+ signal in APAP-treated primary hepatocytes, which was reproduced in HepG2 cells. Quantitative real time PCR showed that APAP-challenged HepG2 cells expressed higher levels of several purinergic receptors, which may explain the hypersensitivity to extracellular ATP. This phenotype was confirmed in humans analyzing liver biopsies from patients diagnosed with acute hepatic failure. Conclusion We suggest that under pathological conditions, ATP may act not only an immune system activator, but also as a paracrine direct cytotoxic DAMP through the dysregulation of Ca2+ homeostasis.

2013-01-01

210

ATP derived from astrocytes modulates memory in the chick.  

PubMed

Memory consolidation in a discriminative bead pecking task is modulated by endogenous adenosine triphosphate (ATP) acting at purinergic receptors in the hippocampus. Consolidation, from short- to intermediate- to long-term memory during two distinct periods following training, was blocked by the non-selective P2 purinergic receptor antagonist PPADS (pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) tetrasodium salt hydrate and the specific P2Y1 receptor antagonist MRS2179. Direct injections of the ATP agonists (ATP?S and ADP?S) potentiated memory consolidation and the effect of ADP?S was blocked by MRS2179, suggesting an important role of ATP on memory consolidation via the P2Y1 receptor in the chick hippocampus. Incubation of astrocytes with ATP?S and ADP?S resulted in the increase of intracellular calcium ([Ca2+]i), the latter being blocked by MRS2179 suggesting a specific role for P2Y1 receptors in the calcium response. This response was prevented by blocking astrocytic oxidative metabolism with fluoroacetate. We argue that the source of the ATP acting on neuronal P2Y1 receptors is most likely to be astrocytes. Thrombin selectively increases [Ca2+]i in astrocytes but not in neurones. The main findings of the present study are: (a) astrocytic [Ca2+]i plays an important role in the consolidation of short-term to long-term memory; and (b) ATP released from chick astrocytes during learning modulates neuronal activity through astrocytic P2Y1 receptors. PMID:22874656

Gibbs, Marie E; Shleper, Maria; Mustafa, Tomris; Burnstock, Geoffrey; Bowser, David N

2012-07-06

211

ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis.  

PubMed Central

In quiescent thymocytes, mitochondrial de-energization was not correlated to apoptotic death. In fact, thymocytes treated with oligomycin, a highly specific inhibitor of ATP synthase, alone or with atractyloside to block ATP translocation from the cytoplasm, were alive, even if their mitochondria were depolarized, as revealed by flow cytometry after Rhodamine 123 staining. Furthermore, oligomycin was a powerful inhibitor of apoptosis induced in rat thymocytes by dexamethasone and, to a lesser extent, by the calcium ionophore A23187 and etoposide, but was without effect when apoptosis was induced by staurosporine, and increased cell death in mitogen-treated thymocytes. The inhibition of apoptosis was confirmed by morphological criteria, inhibition of inter-nucleosomal DNA fragmentation and inhibition of the loss of membrane integrity. The anti-apoptotic effect of oligomycin in cells treated with A23187 or etoposide was correlated to the inhibition of protein synthesis, while inhibition of apoptosis induced by dexamethasone, already evident at an oligomycin concentration of 10 ng/ml, was instead strictly correlated to the effect exerted on the cellular ATP level. Thymocyte apoptosis triggered by dexamethasone was blocked or delayed by inhibitors of respiratory-chain uncouplers, inhibitors of ATP synthase and antioxidants: a lasting protection from dexamethasone-induced apoptosis was always correlated to a drastic and rapid reduction in ATP level (31-35% of control), while a delay in the death process was characterized by a moderate decrease in ATP (73-82% of control). Oligomycin inhibited the specific binding of radioactive corticosteroid to thymocyte nuclei, confirming the inhibitory effect of ATP depletion on glucocorticoid binding and suggesting that ATP depletion is a common mediator of the anti-apoptotic action of different effectors in glucocorticoid-induced apoptosis. In conclusion, the reported data indicate that ATP may act as a cellular modulator of some forms of apoptosis, depending on the death trigger, and that in quiescent cells the de-energization of mitochondria is not necessarily linked to apoptosis.

Stefanelli, C; Bonavita, F; Stanic', I; Farruggia, G; Falcieri, E; Robuffo, I; Pignatti, C; Muscari, C; Rossoni, C; Guarnieri, C; Caldarera, C M

1997-01-01

212

Quantal release of ATP from clusters of PC12 cells  

PubMed Central

Although ATP is important for intercellular communication, little is known about the mechanism of endogenous ATP release due to a dearth of suitable models. Using PC12 cells known to express the P2X2 subtype of ATP receptors and to store ATP with catecholamines inside dense-core vesicles, we found that clusters of PC12 cells cultured for 3–7 days generated small transient inward currents (STICs) after an inward current elicited by exogenous ATP. The amplitude of STICs in individual cells correlated with the peak amplitude of ATP-induced currents. STICs appeared as asynchronous responses (approximately 20 pA average amplitude) for 1–20 s and were investigated with a combination of patch clamping, Ca2+ imaging, biochemistry and electron microscopy. Comparable STICs were produced by focal KCl pulses and were dependent on extracellular Ca2+. STICs were abolished by the P2X antagonist PPADS and potentiated by Zn2+, suggesting they were mediated by P2X2 receptor activation. The highest probability of observing STICs was after the peak of intracellular Ca2+ increase caused by KCl. Biochemical measurements indicated that KCl application induced a significant release of ATP from PC12 cells. Electron microscopy studies showed narrow clefts without ‘synaptic-like’ densities between clustered cells. Our data suggest that STICs were caused by quantal release of endogenous ATP by depolarized PC12 cells in close juxtaposition to the recorded cell. Thus, STICs may be a new experimental model to characterize the physiology of vesicular release of ATP and to study the kinetics and pharmacology of P2X2 receptor-mediated quantal currents.

Fabbro, Alessandra; Skorinkin, Andrei; Grandolfo, Micaela; Nistri, Andrea; Giniatullin, Rashid

2004-01-01

213

Structural Basis for Substrate Binding and the Catalytic Mechanism of Type III Pantothenate Kinase  

SciTech Connect

Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exemplified by the Escherichia coli CoaA protein) and the predominantly eukaryotic type II PanK (PanK-II). PanK-III enzymes have an unusually high K{sub m} for ATP, are resistant to feedback inhibition by CoA, and are unable to utilize the N-alkylpantothenamide family of pantothenate analogues as alternative substrates, thus making type III PanK ineffective in generating CoA analogues as antimetabolites in vivo. Previously, we reported the crystal structure of the PanK-III from Thermotoga maritima and identified it as a member of the 'acetate and sugar kinase/heat shock protein 70/actin' (ASKHA) superfamily. Here we report the crystal structures of the same PanK-III in complex with one of its substrates (pantothenate), its product (phosphopantothenate) as well as a ternary complex structure of PanK-III with pantothenate and ADP. These results are combined with isothermal titration calorimetry experiments to present a detailed structural and thermodynamic characterization of the interactions between PanK-III and its substrates ATP and pantothenate. Comparison of substrate binding and catalytic sites of PanK-III with that of eukaryotic PanK-II revealed drastic differences in the binding modes for both ATP and pantothenate substrates, and suggests that these differences may be exploited in the development of new inhibitors specifically targeting PanK-III.

Yang, Kun; Strauss, Erick; Huerta, Carlos; Zhang, Hong (Stellenbosch); (UTSMC)

2008-07-15

214

Modeling the ATP production in mitochondria.  

PubMed

We revisit here the mathematical model for ATP production in mitochondria introduced recently by Bertram, Pedersen, Luciani, and Sherman (BPLS) as a simplification of the more complete but intricate Magnus and Keizer's model. We identify some inaccuracies in the BPLS original approximations for two flux rates, namely the adenine nucleotide translocator rate JANT and the calcium uniporter rate Juni. We introduce new approximations for such flux rates and then analyze some of the dynamical properties of the model. We infer, from exhaustive numerical explorations, that the enhanced BPLS equations have a unique attractor fixed point for physiologically acceptable ranges of mitochondrial variables and respiration inputs, as one would indeed expect from homeostasis. We determine, in the stationary regime, the dependence of the mitochondrial variables on the respiration inputs, namely the cytosolic concentration of calcium Cac and the substrate fructose 1,6-bisphosphate FBP. The same dynamical effects of calcium and FBP saturations reported for the original BPLS model are observed here. We find out, however, a novel nonstationary effect, which could be, in principle, physiologically interesting: some response times of the model tend to increase considerably for high concentrations of calcium and/or FBP. In particular, the larger the concentrations of Cac and/or FBP, the larger the necessary time to attain homeostasis. PMID:23760661

Saa, Alberto; Siqueira, Kellen M

2013-06-13

215

Regulation of ATP production by mitochondrial Ca2+  

PubMed Central

Stimulation of mitochondrial oxidative metabolism by Ca2+ is now generally recognised as important for the control of cellular ATP homeostasis. Here, we review the mechanisms through which Ca2+ regulates mitochondrial ATP synthesis. We focus on cardiac myocytes and pancreatic ?-cells, where tight control of this process is likely to play an important role in the response to rapid changes in workload and to nutrient stimulation, respectively. We also describe a novel approach for imaging the Ca2+-dependent regulation of ATP levels dynamically in single cells.

Tarasov, Andrei I.; Griffiths, Elinor J.; Rutter, Guy A.

2012-01-01

216

International experience with DSM-III.  

PubMed

The authors investigated various aspects of the international use of and experience with DSM-III through a consultation by mail sponsored by the World Psychiatric Association. The respondents were 175 expert diagnosticians nominated as such by the national psychiatric associations of 52 countries spanning all continents. The United States diagnostic system was used by 72% of the participants, only slightly less than the internationally official International Classification of Diseases, Injuries, and Causes of Death, ninth revision (ICD-9) (77%). Furthermore, DSM-III was perceived to be considerably more useful than the current international classification manual. The leading difficulties encountered with DSM-III involved problematic boundaries or definitions of diagnostic categories and the lack of suitable categories in some cases. The most frequent recommendations offered for the advancement of diagnostic systems included the improvement of patient evaluation procedures, the greater use and refinement of multiaxial diagnosis, and the empirical validation of diagnostic systems. PMID:4067596

Mezzich, J E; Fabrega, H; Mezzich, A C; Coffman, G A

1985-12-01

217

Wide visibility of kilometric type III bursts  

NASA Astrophysics Data System (ADS)

The authors study type III bursts observed at kilometric wavelengths by Planetary Radio Astronomy (PRA) experiment on the Voyagers and type III bursts observed at metric wavelengths from Earth-based observatories. They find metric and kilometric visibility functions consistent with these data and with data published by Dulk et al. (1985). These authors "present evidence that solar type III radio bursts at kilometric wavelengths are visible to a sensitive radio instrument (as is on the ISEE-3 spacecraft) irrespective of the location of the radiating source, be it in front of or behind the Sun". Considering the much lower threshold sensitivity of the near-Earth instrument relative to the PRA near Jupiter, it is concluded that their observation is consistent with the broad yet definitely directive visibility function derived here.

Sawyer, C.; Warwick, J. W.

1987-05-01

218

CT number definition  

NASA Astrophysics Data System (ADS)

The accuracy of CT number plots has been found lacking in several medical applications. This is of concern since the ability to compare and evaluate results on a reproducible and standard basis is essential to long term development. Apart from the technical limitations arising from the CT scanner and the data treatment, there are fundamental issues with the definition of the Hounsfield number, namely the absence of a standard photon energy and the need to specify the attenuation mechanism for standard measurements. This paper presents calculations to demonstrate the shortcomings of the present definition with a brief discussion. The remedy is straightforward, but probably of long duration as it would require an international agreement.

Bryant, J. A.; Drage, N. A.; Richmond, S.

2012-04-01

219

Information systems definition architecture  

SciTech Connect

The Tank Waste Remediation System (TWRS) Information Systems Definition architecture evaluated information Management (IM) processes in several key organizations. The intent of the study is to identify improvements in TWRS IM processes that will enable better support to the TWRS mission, and accommodate changes in TWRS business environment. The ultimate goals of the study are to reduce IM costs, Manage the configuration of TWRS IM elements, and improve IM-related process performance.

Calapristi, A.J.

1996-06-20

220

Definition of Colorado Plateau  

NSDL National Science Digital Library

This site is a brief summary of the Colorado Plateau Province with information about the geology of the area. Also covered in this site are the protected lands on the Colorado Plateau Province, with links to the National Parks, National Monuments, and Wilderness areas of this area. Links within the text lead to definitions of geological terms, and a search box allows users to search within the site.

Wordiq.com

221

Astrocytes protect neurons against methylmercury via ATP/P2Y(1) receptor-mediated pathways in astrocytes.  

PubMed

Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y1 receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6)-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y1 receptor-mediated mechanisms were required because the IL-6 production was (i) inhibited by a P2Y1 receptor antagonist, MRS2179, (ii) abolished in astrocytes obtained from P2Y1 receptor-knockout mice, and (iii) mimicked by exogenously applied ATP. In addition, (iv) MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM) showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A1 receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y1 receptors to upregulate IL-6, thereby leading to A1 receptor-mediated neuro-protection against MeHg. PMID:23469098

Noguchi, Yusuke; Shinozaki, Youichi; Fujishita, Kayoko; Shibata, Keisuke; Imura, Yoshio; Morizawa, Yosuke; Gachet, Christian; Koizumi, Schuichi

2013-02-28

222

The Theory of Definite Automata  

Microsoft Academic Search

A definite automaton is, roughly speaking, an automaton (sequential circuit) with the property that for some fixed integer k its action depends only on the last k inputs. The notion of a definite event introduced by Kleene, as well as the related concepts of definite automata and tables, are studied here in detail. Basic results relating to the minimum number

M. Perles; M. O. Rabin; E. Stiamir

1963-01-01

223

ON CONDITIONALLY DEFINITE QUADRATIC FORMS  

Microsoft Academic Search

Second order optimality conditions may require the verification of a conditional definiteness condition of the formwhere Q(·) is a quadratic form on R and A is an m x n matrix. The prototype case, apart from that of positive definiteness, is that in which A is the n x n identity matrix—in this case the conditionally definite forms are called

D H Martin; D H Jacobson

1982-01-01

224

State Definitions of Emotional Disturbance  

ERIC Educational Resources Information Center

|This article examines definitions state education agencies use to describe the federal education disability called "emotional disturbance." State definitions were collected so that various aspects of them could be analyzed and compared with results of similar studies completed in the 1970s and 1980s. Among results are that state definitions have…

Wery, Jessica J.; Cullinan, Douglas

2013-01-01

225

The Definition of El Niño  

Microsoft Academic Search

A review is given of the meaning of the term El Niño and how it has changed in time, so there is no universal single definition. This needs to be recognized for scientific uses, and precision can only be achieved if the particular definition is identified in each use to reduce the possibility of misunderstanding. For quantitative purposes, possible definitions

Kevin E. Trenberth

1997-01-01

226

Cobalt(III) affinity-labeled aspartokinase. Formation of substrate and inhibitor adducts.  

PubMed

The kinase active site of the aspartokinase-homoserine dehydrogenase enzyme complex of Excherichia coli has been affinity labeled both with substrates aspartate and adenosine triphosphate and feedback inhibitor threonine. Co(III) exchange-inert adducts of aspartokinase and inhibitor or substrates were produced in situ by oxidation of Co(II) with H2O2. Emzyme-Co(III)-adenosine 5'-triphosphate (ATP), enzyme-Co(III)-aspartate, and enzyme-Co(III)-threonine ternary adducts were produced in this manner. The formation of the enzyme-Co(III)-threonine adduct leads us to conclude that threonine inhibits the kinase activity of this enzyme complex by binding in the first coordination sphere of the catalytic metal ion cofactor, a conclusion which is consistent with evidence derived from previous nuclear magnetic resonance data obtained in this laboratory. The quaternary adducts formed by H2O2 oxidation in the presence of aspartokinase, Co(II), ATP, aspartate, and threonine comprised a mixture of both ezyme-Co(III)-ATP-aspartate and enzyme-Co(III)-ATP-threonine adducts. The formation of the quaternary aspartate-containing adduct was unexpected, since the presence of threonine was expected to prevent access of the aspartate to the active site; most significantly however, the the sum of the numbers of aspartate plus threonine molecules incorporated per active site is one. We believe that this shows direct steric overlap between the metal-adjacent binding sites for aspartate and threonine. Aspartate or threonine can not occupy the kinase active site simultaneously; this conclusion is consistent with the direct competitive inhibition of aspartate by threonine observed in steady-state kinetic studies. PMID:182215

Wright, J K; Feldman, J; Takahashi, M

1976-08-24

227

Adenosine triphosphate (ATP) in the marine environment: a bibliography  

Microsoft Academic Search

This bibliography lists published works on adenosine triphosphate (ATP) detected in the marine environment. Over 100 citations are listed in four categories: field measurements; macroscopic organisms; benthic populations; and papers on analytical methods.

A. T. Jones; E. O. Hartwig; M. S. Quinby-Hunt

1981-01-01

228

Adenosine triphosphate (ATP) in the marine environment: a bibliography  

SciTech Connect

This bibliography lists published works on adenosine triphosphate (ATP) detected in the marine environment. Over 100 citations are listed in four categories: field measurements; macroscopic organisms; benthic populations; and papers on analytical methods.

Jones, A.T.; Hartwig, E.O.; Quinby-Hunt, M.S.

1981-03-01

229

Suggested mitochondrial ancestry of nonmitochondrial ATP\\/ADP carrier  

Microsoft Academic Search

One of the major evolutionary events that transformed an endosymbiotic bacterium into a mitochondrion was the acquisition\\u000a of the ATP\\/ADP carrier (AAC) in order to supply the host with respiration-derived ATP. Along with the mitochondrial carrier,\\u000a an unrelated carrier is known, which is characteristic of intracellular chlamydiae, plastids, parasitic intracellular eukaryote\\u000a Encephalitozoon cuniculi, and the genus Rickettsia of obligate endosymbiotic

V. V. Emelyanov

2007-01-01

230

The ATP-binding cassette family: a structural perspective  

Microsoft Academic Search

The ATP-binding cassette family is one of the largest groupings of membrane proteins, moving allocrites across lipid membranes,\\u000a using energy from ATP. In bacteria, they reside in the inner membrane and are involved in both uptake and export. In eukaryotes,\\u000a these transporters reside in the cell’s internal membranes as well as in the plasma membrane and are unidirectional—out of\\u000a the

Veronica Kos; Robert Curtis Ford

2009-01-01

231

Connexins Regulate Calcium Signaling by Controlling ATP Release  

Microsoft Academic Search

Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca2+ mobilization and was inhibited by Cl- channel blockers. Calcium wave

Maria Luisa Cotrina; Jane H.-C. Lin; Alexandra Alves-Rodrigues; Shujun Liu; Jiang Li; Hooman Azmi-Ghadimi; Jian Kang; Christian C. G. Naus; Maiken Nedergaard

1998-01-01

232

Extracellular ATP stimulates NO production in rat thick ascending limb.  

PubMed

NO produced by NO synthase (NOS) 3 acts as an autacoid to regulate NaCl absorption in the thick ascending limb. ATP induces NO production by NOS 3 in endothelial cells. We hypothesized that extracellular ATP activates NOS in thick ascending limbs through P2 receptors. To test this, we measured intracellular NO production using the NO-selective fluorescent dye DAF-2 in suspensions of rat medullary thick ascending limbs. We found that ATP increased DAF-2 fluorescence in a concentration-dependent manner, reaching saturation at &200 micromol/L with an EC50 of 37 micromol/L. The increase was blunted by 74% by the nonselective NOS inhibitor L-omega-nitro-arginine-methyl-ester (2 mmol/L; 60+/-7 versus 16+/-6 arbitrary fluorescence units; P<0.02; n=5). In the presence of the P2 receptor antagonist suramin (300 micromol/L), ATP-induced NO production was reduced by 64% (101+/-11 versus 37+/-5 arbitrary fluorescence units; P<0.002; n=5). Blocking ATP hydrolysis with a 5'-ectonucleotidase inhibitor, ARL67156 (30 micromol/L) enhanced the response to ATP and shifted the EC(50) to 0.8 micromol/L. In the presence of ARL67156, the EC50 of the P2X-selective agonist beta,gamma-methylene-adenosine 5'-triphosphate was 4.8 micromol/L and the EC50 for the P2Y-selective agonist UTP was 40.4 micromol/L. The maximal responses for both agonists were similar. Taken together, these data indicate that ATP stimulates NO production in the thick ascending limb primarily through P2X receptor activation and that ATP hydrolysis may regulate NO production. PMID:16380539

Silva, Guillermo; Beierwaltes, William H; Garvin, Jeffrey L

2005-12-27

233

Clinical application of adenosine and ATP for pain control  

Microsoft Academic Search

This review summarizes clinical application of adenosine and adenosine 5?-triphosphate (ATP) in pain conditions. Investigations have been performed in patients with acute perioperative pain or chronic neuropathic pain treated with intravenous adenosine or ATP, or intrathecal adenosine. Characteristic central adenosine A1 receptor-mediated pain-relieving effects have been observed after intravenous adenosine infusion in human inflammation\\/sensitization pain models and in patients with

Masakazu Hayashida; Ken-ichi Fukuda; Atsuo Fukunaga

2005-01-01

234

ATP mediates fast synaptic transmission in mammalian neurons  

Microsoft Academic Search

IN addition to its diverse functions inside cells, ATP can act at several types of cell-surface receptor1-3. One of these (P2x-purinoceptor) is believed to be a ligand-gated cation channel1-6. The presence of P2x receptors on autonomic, sensory and central neurons suggests that ATP might be released to act as a fast excitatory synaptic transmitter. Here we record excitatory synaptic potentials

Richard J. Evans; Victor Derkach; Annmarie Surprenant

1992-01-01

235

ATP-regulated K+ channels in cardiac muscle  

Microsoft Academic Search

An outward current of unknown nature increases significantly when cardiac cells are treated with cyanide or subjected to hypoxia1-4, and decreases on intracellular injection of ATP5. We report here that application of the patch-clamp technique to CN-treated mammalian heart cells reveals specific K+ channels which are depressed by intracellular ATP (ATPi) at levels greater than 1 mM. For these channels,

A. Noma

1983-01-01

236

Functional studies of ATP sulfurylase from Penicillium chrysogenum  

Microsoft Academic Search

ATP sulfurylase from Penicillium chrysogenum has a specific activity (V\\/sub max\\/) of 6-7 units x mg protein⁻¹ determined with the physiological substrates of MgATP and SOâ\\/sup 2 -\\/ and assayed by (A) initial velocity measurements with APS kinase and inorganic pyrophosphatase present and (B) analysis of nonlinear reaction progress curves. The fact both assays give the same results show the

Seubert

1985-01-01

237

ATP-Dependent Ca2+ uptake into Plant Membrane Vesicles  

Microsoft Academic Search

Membrane vesicles were extracted from etiolated and light-grown plants, a plant cell suspension culture, and an alga. Upon addition of ATP and Mg2+, active Ca2+ uptake into the vesicles against a concentration gradient was shown. The dependence of this uptake on ATP and Mg2+ concentrations, pH, and temperature is described. In the absence of oxalate, equilibrium between Ca2+ uptake and

Joachim Gross; Dieter Marme

1978-01-01

238

ATP-citrate lyase activity in fungal extracts  

Microsoft Academic Search

ATP-citrate lyase activity has been demonstrated in crude extracts from several species ofMortierella. This filamentous fungus characteristically stores lipid in the mycelium. The enzyme catalyses an ATP-dependent cleavage\\u000a of citrate in the presence of CoA to oxaloacetic acid and acetylCoA. A partially purified preparation has been obtained and\\u000a shown to have properties similar to preparations isolated from other sources. It

Margaret M. Attwood

1973-01-01

239

Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP  

PubMed Central

Dicer is a multi-domain RNase III-related endonuclease responsible for processing double-stranded RNA (dsRNA) to small interfering RNAs (siRNAs) during a process of RNA interference (RNAi). It also catalyses excision of the regulatory microRNAs from their precursors. In this work, we describe the purification and properties of a recombinant human Dicer. The protein cleaves dsRNAs into ?22 nucleotide siRNAs. Accumulation of processing intermediates of discrete sizes, and experiments performed with substrates containing modified ends, indicate that Dicer preferentially cleaves dsRNAs at their termini. Binding of the enzyme to the substrate can be uncoupled from the cleavage step by omitting Mg2+ or performing the reaction at 4°C. Activity of the recombinant Dicer, and of the endogenous protein present in mammalian cell extracts, is stimulated by limited proteolysis, and the proteolysed enzyme becomes active at 4°C. Cleavage of dsRNA by purifed Dicer and the endogenous enzyme is ATP independent. Additional experiments suggest that if ATP participates in the Dicer reaction in mammalian cells, it might be involved in product release needed for the multiple turnover of the enzyme.

Zhang, Haidi; Kolb, Fabrice A.; Brondani, Vincent; Billy, Eric; Filipowicz, Witold

2002-01-01

240

Requirement for ATP by the DNA damage checkpoint clamp loader.  

PubMed

The DNA damage clamp loader replication factor C (RFC-Rad24) consists of the Rad24 protein and the four small Rfc2-5 subunits of RFC. This complex loads the heterotrimeric DNA damage clamp consisting of Rad17, Mec3, and Ddc1 (Rad17/3/1) onto partial duplex DNA in an ATP-dependent manner. Interactions between the clamp loader and the clamp have been proposed to mirror those of the replication clamp loader RFC and the sliding clamp proliferating cell nuclear antigen (PCNA). In that system, three ATP molecules bound to the Rfc2, Rfc3, and Rfc4 subunits are necessary and sufficient for efficient loading of PCNA, whereas ATP binding to Rfc1 is not required. In contrast, in this study, we show that mutant RFC-Rad24 with a rad24-K115E mutation in the ATP-binding domain of Rad24 shows defects in the ATPase of the complex and is defective for interaction with Rad17/3/1 and for loading of the checkpoint clamp. A similar defect was measured with a mutant RFC-Rad24 clamp loader carrying a rfc4K55R ATP-binding mutation, whereas the rfc4K55E clamp loader showed partial loading activity, in agreement with genetic studies of these mutants. These studies show that ATP utilization by the checkpoint clamp/clamp loader system is effectively different from that by the structurally analogous replication system. PMID:15014082

Majka, Jerzy; Chung, Brian Y; Burgers, Peter M J

2004-03-09

241

Human prostasomes express glycolytic enzymes with capacity for ATP production.  

PubMed

Prostasomes are prostate-derived, exosome-like microvesicles that transmit signaling complexes between the acinar epithelial cells of the prostate and sperm cells. The vast majority of prostasomes have a diameter of 30-200 nm, and they are generally surrounded by a classical membrane bilayer. Using a selected proteomic approach, it became increasingly clear that prostasomes harbor distinct subsets of proteins that may be linked to adenosine triphosphate (ATP) metabolic turnover that in turn might be of importance in the role of prostasomes as auxiliary instruments in the fertilization process. Among the 21 proteins identified, most of the enzymes of anaerobic glycolysis were represented, and three of the glycolytic enzymes present are among the top 10 proteins found in most exosomes, once again linking prostasomes to the exosome family. Other prostasomal enzymes involved in ATP turnover were adenylate kinase, ATPase, 5'-nucleotidase, and hexose transporters. The identified enzymes in their prostasomal context were operational for ATP formation when supplied with substrates. The net ATP production was low due to a high prostasomal ATPase activity that could be partially inhibited by vanadate that was utilized to profile the ATP-forming ability of prostasomes. Glucose and fructose were equivalent as glycolytic substrates for prostasomal ATP formation, and the enzymes involved were apparently surface located on prostasomes, since an alternative substrate not being membrane permeable (glyceraldehyde 3-phosphate) was operative, too. There is no clear-cut function linked to this subset of prostasomal proteins, but some possible roles are discussed. PMID:23341497

Ronquist, K Göran; Ek, Bo; Stavreus-Evers, Anneli; Larsson, Anders; Ronquist, Gunnar

2013-01-22

242

Characterization of domain interfaces in monomeric and dimeric ATP synthase.  

PubMed

We disassembled monomeric and dimeric yeast ATP synthase under mild conditions to identify labile proteins and transiently stable subcomplexes that had not been observed before. Specific removal of subunits alpha, beta, oligomycin sensitivity conferring protein (OSCP), and h disrupted the ATP synthase at the gamma-alpha(3)beta(3) rotor-stator interface. Loss of two F(1)-parts from dimeric ATP synthase led to the isolation of a dimeric subcomplex containing membrane and peripheral stalk proteins thus identifying the membrane/peripheral stalk sectors immediately as the dimerizing parts of ATP synthase. Almost all subunit a was found associated with a ring of 10 c-subunits in two-dimensional blue native/SDS gels. We therefore postulate that c10a1-complex is a stable structure in resting ATP synthase until the entry of protons induces a breaking of interactions and stepwise rotation of the c-ring relative to the a-subunit in the catalytic mechanism. Dimeric subunit a was identified in SDS gels in association with two c10-rings suggesting that a c10a2c10-complex may constitute an important part of the monomer-monomer interface in dimeric ATP synthase that seems to be further tightened by subunits b, i, e, g, and h. In contrast to the monomer-monomer interface, the interface between dimers in higher oligomeric structures remains largely unknown. However, we could show that the natural inhibitor protein Inh1 is not required for oligomerization. PMID:18245802

Wittig, Ilka; Velours, Jean; Stuart, Rosemary; Schägger, Hermann

2008-02-02

243

Characterization of the mitochondrial ATP synthase from yeast Saccharomyces cerevisae.  

PubMed

The mitochondrial ATP synthase from yeast S. cerevisiae has been genetically modified, purified in a functional form, and characterized with regard to lipid requirement, compatibility with a variety of detergents, and the steric limit with rotation of the central stalk has been assessed. The ATP synthase has been modified on the N-terminus of the ?-subunit to include a His(6) tag for Ni-chelate affinity purification. The enzyme is purified by a two-step procedure from submitochondrial particles and the resulting enzyme demonstrates lipid dependent oligomycin sensitive ATPase activity of 50 units/mg. The yeast ATP synthase shows a strong lipid selectivity, with cardiolipin (CL) being the most effective activating lipid and there are 30 moles CL bound per mole enzyme at saturation. Green Fluorescent Protein (GFP) has also been fused to the C-terminus of the ?-subunit to create a steric block for rotation of the central stalk. The ?-GFP fusion peptide is imported into the mitochondrion, assembled with the ATP synthase, and inhibits ATP synthetic and hydrolytic activity of the enzyme. F(1)F(o) ATP synthase with ?-GFP was purified to homogeneity and serves as an excellent enzyme for two- and three-dimensional crystallization studies. PMID:21748405

Pagadala, Vijayakanth; Vistain, Luke; Symersky, Jindrich; Mueller, David M

2011-07-12

244

Structural basis for the ATP-induced isomerization of kinesin.  

PubMed

Kinesin superfamily proteins (KIFs) are microtubule-based molecular motors driven by the energy derived from the hydrolysis of ATP. Previous studies have revealed that the ATP binding step is crucial both for the power stroke to produce motility and for the inter-domain regulation of ATPase activity to guarantee the processive movement of dimeric KIFs. Here, we report the first crystal structure of KIF4 complexed with the non-hydrolyzable ATP analog, AMPPNP (adenylyl imidodiphosphate), at 1.7Å resolution. By combining our structure with previously solved KIF1A structures complexed with two ATP analogs, molecular snapshots during ATP binding reveal that the closure of the nucleotide-binding pocket during ATP binding is achieved by closure of the backdoor. Closure of the backdoor stabilizes two mobile regions, switch I and switch II, to generate the phosphate tube from which hydrolyzed phosphate is released. Through the stabilization of switch II, the local conformational change at the catalytic center is further relayed to the neck-linker element that fully docks to the catalytic core to produce the power stroke. Because the neck linker is a sole element that connects the partner heads in dimeric KIFs, this tight structural coordination between the catalytic center and neck linker enables inter-domain communication between the partner heads. This study also revealed the putative microtubule-binding site of KIF4, thus providing structural insights that describe the specific binding of KIF4 to the microtubule. PMID:23500491

Chang, Qing; Nitta, Ryo; Inoue, Shigeyuki; Hirokawa, Nobutaka

2013-03-07

245

Characterization of the mitochondrial ATP synthase from yeast Saccharomyces cerevisae  

PubMed Central

The mitochondrial ATP synthase from yeast S. cerevisiae has been genetically modified, purified in a functional form, and characterized with regard to lipid requirement, compatibility with a variety of detergents, and the steric limit with rotation of the central stalk has been assessed. The ATP synthase has been modified on the N-terminus of the ?-subunit to include a His6 tag for Ni-chelate affinity purification. The enzyme is purified by a two-step procedure from submitochondrial particles and the resulting enzyme demonstrates lipid dependent oligomycin sensitive ATPase activity of 50 units/mg. The yeast ATP synthase shows a strong lipid selectivity, with cardiolipin (CL) being the most effective activating lipid and there are 30 moles CL bound per mole enzyme at saturation. Green Fluorescent Protein (GFP) has also been fused to the C-terminus of the ?-subunit to create a steric block for rotation of the central stalk. The ?-GFP fusion peptide is imported into the mitochondrion, assembled with the ATP synthase, and inhibits ATP synthetic and hydrolytic activity of the enzyme. F1Fo ATP synthase with ?-GFP was purified to homogeneity and serves as an excellent enzyme for two- and three-dimensional crystallization studies.

Pagadala, Vijayakanth; Vistain, Luke; Symersky, Jindrich; Mueller, David M.

2013-01-01

246

A High-Throughput TNP-ATP Displacement Assay for Screening Inhibitors of ATP-Binding in Bacterial Histidine Kinases  

PubMed Central

Abstract Bacterial histidine kinases (HK) are members of the GHKL superfamily, which share a unique adenosine triphosphate (ATP)-binding Bergerat fold. Our previous studies have shown that Gyrase, Hsp90, MutL (GHL) inhibitors bind to the ATP-binding pocket of HK and may provide lead compounds for the design of novel antibiotics targeting these kinases. In this article, we developed a competition assay using the fluorescent ATP analog, 2?,3?-O-(2,4,6-trinitrophenyl) adenosine 5?-triphosphate. The method can be used for high-throughput screening of compound libraries targeting HKs or other ATP-binding proteins. We utilized the assay to screen a library of GHL inhibitors targeting the bacterial HK PhoQ, and discuss the applications of the 2?,3?-O-(2,4,6-trinitrophenyl) adenosine 5?-triphosphate competition assay beyond GHKL inhibitor screening.

Guarnieri, Michael T.; Blagg, Brian S. J.

2011-01-01

247

Welding, terms and definitions  

SciTech Connect

This book provides a dictionary of the technical language used in the welding industry. Its purpose is to establish standard terms to aid in the communication of welding information. Since it is intended to be a comprehensive compilation of welding terminology, nonstandard terms used in the welding industry are also included. All terms are either standard or non-standard. They are arranged in the conventional dictionary letter-by-letter alphabetical sequence. A total of 946 terms are defined and the definitions are illustrated by 41 Figures. Also included is the Master Chart of Welding and Allied Processes and the Joining Method Diagram with corollary classification diagrams.

Not Available

1985-01-01

248

Unit Replacement System Analysis III (URSA III).  

National Technical Information Service (NTIS)

The USRA III Study is to assist HQDA in transitioning from an individual to a unit replacement system. The assignment of combat arms battalions to regiments resulted in unequal career opportunities for soldiers serving in those positions. Combat arms posi...

C. B. Torres

1983-01-01

249

ATP stimulated catecholamine secretion: Response in perfused adrenal glands and a subpopulation of cultured chromaffin cells  

Microsoft Academic Search

Extracellular ATP is shown to induce catecholamine secretion in bovine chromaffin cells. Our data indicate that cells in culture gradually increase their response to ATP, and we have separated freshly isolated cells on a density gradient and found that the lighter cells develop a much stronger response to ATP than do the heavier cells. To see if the ATP sensitivity

Lih Fang Lin; Marga C. Bott; Lung-Sen Kao; Edward W. Westhead

1995-01-01

250

New Developments in Bioluminescence Technology: Detection of Microbial ATP in Biopharmaceutical In-Process Materials  

Microsoft Academic Search

ATP bioluminescence is a widely accepted method for rapid microbial screening of raw materials, in-process and finished products. Many bioprocessing samples contain high levels of non-microbial ATP that need to be reduced before microbial ATP can be reliably detected. Due to this limitation, standard ATP bioluminescence technology has not been widely applied to biopharmaceutical sample types. New developments address the

L. Daane; A. Hearn

251

cDNA, genomic sequence cloning and overexpression of giant panda (Ailuropoda melanoleuca) mitochondrial ATP synthase ATP5G1.  

PubMed

The ATP5G1 gene is one of the three genes that encode mitochondrial ATP synthase subunit c of the proton channel. We cloned the cDNA and determined the genomic sequence of the ATP5G1 gene from the giant panda (Ailuropoda melanoleuca) using RT-PCR technology and touchdown-PCR, respectively. The cloned cDNA fragment contains an open reading frame of 411 bp encoding 136 amino acids; the length of the genomic sequence is of 1838 bp, containing three exons and two introns. Alignment analysis revealed that the nucleotide sequence and the deduced protein sequence are highly conserved compared to Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, and Sus scrofa. The homologies for nucleotide sequences of the giant panda ATP5G1 to those of these species are 93.92, 92.21, 92.46, 93.67, and 92.46%, respectively, and the homologies for amino acid sequences are 90.44, 95.59, 93.38, 94.12, and 91.91%, respectively. Topology prediction showed that there is one protein kinase C phosphorylation site, one casein kinase II phosphorylation site, five N-myristoylation sites, and one ATP synthase c subunit signature in the ATP5G1 protein of the giant panda. The cDNA of ATP5G1 was transfected into Escherichia coli, and the ATP5G1 fused with the N-terminally GST-tagged protein gave rise to accumulation of an expected 40-kDa polypeptide, which had the characteristics of the predicted protein. PMID:23007995

Hou, W-R; Hou, Y-L; Ding, X; Wang, T

2012-09-03

252

Trafficking of the copper-ATPases, ATP7A and ATP7B: Role in copper homeostasis  

Microsoft Academic Search

Copper is essential for human health and copper imbalance is a key factor in the aetiology and pathology of several neurodegenerative diseases. The copper-transporting P-type ATPases, ATP7A and ATP7B are key molecules required for the regulation and maintenance of mammalian copper homeostasis. Their absence or malfunction leads to the genetically inherited disorders, Menkes and Wilson diseases, respectively. These proteins have

Sharon La Fontaine; Julian F. B. Mercer

2007-01-01

253

Characterization of a Baculovirus-Encoded ATP-Dependent DNA Ligase†  

PubMed Central

Sequence analysis of the Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV) genome identified an open reading frame (ORF) encoding a 548-amino-acid (62-kDa) protein that showed 35% amino acid sequence identity with vaccinia virus ATP-dependent DNA ligase. Ligase homologs have not been reported from other baculoviruses. The ligase ORF was cloned and expressed as an N-terminal histidine-tagged fusion protein. Incubation of the purified protein with [?-32P]ATP resulted in formation of a covalent enzyme-adenylate intermediate which ran as a 62-kDa labeled band on a sodium dodecyl sulfate-polyacrylamide gel. Loss of the radiolabeled band occurred upon incubation of the intermediate with pyrophosphate, poly(dA) · poly(dT)12–18, or poly(rA) · poly(dT)12–18, characteristics of a DNA ligase II or III. The protein was able to ligate a double-stranded synthetic DNA substrate containing a single nick and inefficiently ligated a 1-nucleotide (nt) gap but did not ligate a 2-nt gap. It was able to ligate short, complementary overhangs but not blunt-ended double-stranded DNA. In a transient DNA replication assay employing six plasmids containing the LdMNPV homologs of the essential baculovirus replication genes, a plasmid containing the DNA ligase gene was neither essential nor stimulatory. All of these results are consistent with the activity of type III DNA ligases, which have been implicated in DNA repair and recombination.

Pearson, Margot N.; Rohrmann, George F.

1998-01-01

254

45 CFR 81.131 - Definitions.  

Code of Federal Regulations, 2011 CFR

... 2011-10-01 2011-10-01 false Definitions. 81.131 Section 81.131 Public Welfare...PROCEDURE FOR HEARINGS UNDER PART 80 OF THIS TITLE Definitions § 81.131 Definitions. The definitions contained in §...

2011-10-01

255

45 CFR 81.131 - Definitions.  

Code of Federal Regulations, 2012 CFR

... 2012-10-01 2012-10-01 false Definitions. 81.131 Section 81.131 Public Welfare...PROCEDURE FOR HEARINGS UNDER PART 80 OF THIS TITLE Definitions § 81.131 Definitions. The definitions contained in §...

2012-10-01

256

49 CFR 1101.1 - Statutory definitions.  

Code of Federal Regulations, 2012 CFR

... 2012-10-01 false Statutory definitions. 1101.1 Section 1101.1 Transportation...TRANSPORTATION RULES OF PRACTICE DEFINITIONS AND CONSTRUCTION § 1101.1 Statutory definitions. The definitions contained in...

2012-10-01

257

49 CFR 1101.1 - Statutory definitions.  

Code of Federal Regulations, 2011 CFR

... 2011-10-01 false Statutory definitions. 1101.1 Section 1101.1 Transportation...TRANSPORTATION RULES OF PRACTICE DEFINITIONS AND CONSTRUCTION § 1101.1 Statutory definitions. The definitions contained in...

2011-10-01

258

Dexamethasone Enhances ATP-Induced Inflammatory Responses in Endothelial Cells  

PubMed Central

The purinergic nucleotide ATP is released from stressed cells and is implicated in vascular inflammation. Glucocorticoids are essential to stress responses and are used therapeutically, yet little information is available that describes the effects of glucocorticoids on ATP-induced inflammation. In a human microvascular endothelial cell line, extracellular ATP-induced interleukin (IL)-6 secretion in a dose- and time-dependent manner. When cells were pretreated with dexamethasone, a prototypic glucocorticoid, ATP-induced IL-6 production was enhanced in a time- and dose-dependent manner. Mifepristone, a glucocorticoid receptor antagonist, blocked these effects. ATP-induced IL-6 release was significantly inhibited by a phospholipase C inhibitor [1-[6-[((17?)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)] (63.2 ± 3%, p < 0.001) and abolished by a p38 mitogen-activated protein kinase inhibitor [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB 203580)] (88 ± 1%, p < 0.001). Cells treated with dexamethasone induced mRNA expression of the purinergic P2Y2 receptor (P2Y2R) 1.8- ± 0.1-fold and, when stimulated with ATP, enhanced Ca2+ release and augmented IL-6 mRNA expression. Silencing of the P2Y2R by its small interfering RNA decreased ATP-induced IL-6 production by 81 ± 1% (p < 0.001). Dexamethasone enhanced the transcription rate of P2Y2R mRNA and induced a dose-related increase in the activity of the P2Y2R promoter. Furthermore, dexamethasone-enhanced ATP induction of adhesion molecule transcription and augmented the release of IL-8. Dexamethasone leads to an unanticipated enhancement of endothelial inflammatory mediator production by extracellular ATP via a P2Y2R-dependent mechanism. These data define a novel positive feedback loop of glucocorticoids and ATP-induced endothelial inflammation.

Ding, Yi; Gao, Zhan-Guo; Jacobson, Kenneth A.

2010-01-01

259

Observation of Mg2+.ATP and uncomplexed ATP in slow exchange by 31P-NMR at high magnetic fields.  

PubMed

The 31P-NMR lines of the beta-phosphate groups in Mg2+.ATP and in metalfree ATP can be observed separately up to 280 K at 8.5 T and up to 285 K at 11.7 T. At 274 K and 8.5 T the beta-phosphorous resonances are in slow exchange at pH values above pH 5, the gamma-phosphorous resonances are in slow exchange only near pH 6, but in fast exchange at low and high pH-values. The fast exchange condition holds for the alpha-phosphorous resonances over the entire pH-range. For Ca2+.ATP and metalfree ATP always fast exchange prevails down to the freezing point of water even at 11.7 T. Based on the separate observation of the 31P-NMR signals of Mg2+.ATP and uncomplexed ATP new experiments are proposed and possible sources of error in 'in vivo' NMR studies are discussed. PMID:3484953

Sontheimer, G M; Kuhn, W; Kalbitzer, H R

1986-02-13

260

Glucose Triggers ATP Secretion from Bacteria in a Growth-Phase-Dependent Manner  

PubMed Central

ATP modulates immune cell functions, and ATP derived from gut commensal bacteria promotes the differentiation of T helper 17 (Th17) cells in the intestinal lamina propria. We recently reported that Enterococcus gallinarum, isolated from mice and humans, secretes ATP. We have since found and characterized several ATP-secreting bacteria. Of the tested enterococci, Enterococcus mundtii secreted the greatest amount of ATP (>2 ?M/108 cells) after overnight culture. Glucose, not amino acids and vitamins, was essential for ATP secretion from E. mundtii. Analyses of energy-deprived cells demonstrated that glycolysis is the most important pathway for bacterial ATP secretion. Furthermore, exponential-phase E. mundtii and Enterococcus faecalis cells secrete ATP more efficiently than stationary-phase cells. Other bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, also secrete ATP in exponential but not stationary phase. These results suggest that various gut bacteria, including commensals and pathogens, might secrete ATP at any growth phase and modulate immune cell function.

Hironaka, Ippei; Iwase, Tadayuki; Sugimoto, Shinya; Okuda, Ken-ichi; Tajima, Akiko; Yanaga, Katsuhiko

2013-01-01

261

Two distinct proton binding sites in the ATP synthase family.  

PubMed

The F1F0 ATP synthase utilizes energy stored in an electrochemical gradient of protons (or Na+ ions) across the membrane to synthesize ATP from ADP and phosphate. Current models predict that the protonation/deprotonation of specific acidic c ring residues is at the core of the proton translocation mechanism by this enzyme. To probe the mode of proton binding, we measured the covalent modification of the acidic c ring residues with the inhibitor dicyclohexylcarbodiimide (DCCD) over the pH range from 5 to 11. With the H+-translocating ATP synthase from the archaeum Halobacterium salinarium or the Na+-translocating ATP synthase from Ilyobacter tartaricus, the pH profile of DCCD labeling followed a titration curve with a pKa around neutral, reflecting protonation of the acidic c ring residues. However, with the ATP synthases from Escherichia coli, mitochondria, or chloroplasts, a clearly different, bell-shaped pH profile for DCCD labeling was observed which is not compatible with carboxylate protonation but might be explained by the coordination of a hydronium ion as proposed earlier [Boyer, P. D. (1988) Trends Biochem. Sci. 13, 5-7]. Upon site-directed mutagenesis of single binding site residues of the structurally resolved c ring, the sigmoidal pH profile for DCCD labeling could be converted to a more bell-shaped one, demonstrating that the different ion binding modes are based on subtle changes in the amino acid sequence of the protein. The concept of two different binding sites in the ATP synthase family is supported by the ATP hydrolysis pH profiles of the investigated enzymes. PMID:17910472

von Ballmoos, Christoph; Dimroth, Peter

2007-10-02

262

Heat shock protein 70 (Hsp70) inhibits oxidative phosphorylation and compensates ATP balance through enhanced glycolytic activity  

PubMed Central

To address possible effects of heat shock protein 70 (Hsp70) on energy metabolism, we established a cell line expressing different levels of Hsp70 and evaluated changes in glucose and lactate metabolites, as well as ATP levels accordingly. In addition, activities of enzymes involved in glycolysis [phosphofructokinase (PFK) and lactate dehydrogenase (LDH)], Krebs cycle [citric synthase (CS)], and oxidative phosphorylation {NADH dehydrogenase [complex I (CI)] and ubiquinol:cytochrome-c reductase [complex III (CIII)]} were analyzed. The results show that both glucose consumption and lactate excretion were elevated significantly in cells expressing increased levels of Hsp70. Simultaneously, the activities of glycolytic enzymes PFK and LDH were increased markedly in cells overexpressing Hsp70. Activities of enzymes CI and CIII, both involved in oxidative phosphorylation, decreased upon increased expression of Hsp70. These findings were supported by nonsignificant reductions of CS activities in cells that overexpressed Hsp70, whereas intracellular ATP levels remained constant over a wide range of Hsp70 expression. In conclusion, overexpression of Hsp70 in HeLa cells results in downregulation of oxidative phosphorylation, in particular, multiprotein CIII, the main source of reactive oxygen species. In exchange, upregulation of the glycolytic pathway compensates for the homeostasis of cellular ATP supply.

Wang, Liangli; Schumann, Uwe; Prokopchuk, Olga; Steinacker, Jurgen M.

2012-01-01

263

Copper-dependent interaction of glutaredoxin with the N termini of the copper-ATPases (ATP7A and ATP7B) defective in Menkes and Wilson diseases  

Microsoft Academic Search

The P-type ATPases affected in Menkes and Wilson diseases, ATP7A and ATP7B, respectively, are key copper transporters that regulate copper homeostasis. The N termini of these proteins are critical in regulating their function and activity, and contain six copper-binding motifs MxCxxC. In this study, we describe the identification of glutaredoxin (GRX1) as an interacting partner of both ATP7A and ATP7B,

Chris M. Lim; Michael A. Cater; Julian F. B. Mercer; Sharon La Fontaine

2006-01-01

264

Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells  

Microsoft Academic Search

BACKGROUND: Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant,

Ganna V Kalayda; Christina H Wagner; Irina Buß; Jan Reedijk; Ulrich Jaehde

2008-01-01

265

Modulation of the Cellular Pharmacology of Cisplatin and Its Analogs by the Copper Exporters ATP7A and ATP7B  

Microsoft Academic Search

The copper efflux transporters ATP7A and ATP7B sequester intracellular copper into the vesicular secretory pathway for export from the cell. The influence of these transporters on the pharmacodynamics of cisplatin, carboplatin, and oxaliplatin was investigated using human Menkes' disease fibroblasts (Me32a) that do not express either transporter and sublines molecularly engineered to express either ATP7A (MeMNK) or ATP7B (MeWND). Cellular

Goli Samimi; Kuniyuki Katano; Alison K. Holzer; Roohangiz Safaei; Stephen B. Howell

2004-01-01

266

Sociocultural definitions of risk  

SciTech Connect

Public constituencies frequently are criticized by technical experts as being irrational in response to low-probability risks. This presentation argued that most people are concerned with a variety of risk attributes other than probability and that is rather irrational to exclude these from the definition and analysis of technological risk. Risk communication, which is at the heart of the right-to-know concept, is described as the creation of shared meaning rather than the mere transmission of information. A case study of utilities, public utility commissions, and public interest groups illustrates how the diversity of institutional cultures in modern society leads to problems for the creation of shared meanings in establishing trust, distributing liability, and obtaining consent to risk. This holistic approach to risk analysis is most appropriate under conditions of high uncertainty and/or decision stakes. 1 fig., 5 tabs.

Rayner, S.

1990-10-01

267

Two definitions for genders  

NASA Astrophysics Data System (ADS)

By my definition, man and woman are the same fact to say. So man and woman have the same thinkings and same existence. But when I say again for man and woman, they are different for sex as the two different persons. They are different each two persons. As an example, by quantum, sex and color is different (the same existence and also different kind with quantum way-push and pull at the same time), also they are the same as they are our ID (hormones) and also dream matter. The same way, I hope we go to heaven and god will say you are the truth like it to be after the end of the world. I wish man and woman are different as it is more fun.

Shin, Philip

2011-10-01

268

Skeletal muscle ATP kinetics are impaired in frail mice.  

PubMed

The interleukin-10 knockout mouse (IL10(tm/tm)) has been proposed as a model for human frailty, a geriatric syndrome characterized by skeletal muscle (SM) weakness, because it develops an age-related decline in SM strength compared to control (C57BL/6J) mice. Compromised energy metabolism and energy deprivation appear to play a central role in muscle weakness in metabolic myopathies and muscular dystrophies. Nonetheless, it is not known whether SM energy metabolism is altered in frailty. A combination of in vivo (31)P nuclear magnetic resonance experiments and biochemical assays was used to measure high-energy phosphate concentrations, the rate of ATP synthesis via creatine kinase (CK), the primary energy reserve reaction in SM, as well as the unidirectional rates of ATP synthesis from inorganic phosphate (Pi) in hind limb SM of 92-week-old control (n?=?7) and IL10(tm/tm) (n?=?6) mice. SM Phosphocreatine (20.2?±?2.3 vs. 16.8?±?2.3 ?mol/g, control vs. IL10(tm/tm), p?ATP flux via CK (5.0?±?0.9 vs. 3.1?±?1.1 ?mol/g/s, p?ATP synthesis from inorganic phosphate (Pi???ATP) (0.58?±?0.3 vs. 0.26?±?0.2 ?mol/g/s, p?ATP hydrolysis (?G ?ATP) were significantly lower and [Pi] (2.8?±?1.0 vs. 5.3?±?2.0 ?mol/g, control vs. IL10(tm/tm), p?ATP kinetics, high-energy phosphate levels and energy release from ATP hydrolysis are reduced and inorganic phosphate is elevated in a murine model of frailty. These observations do not prove, but are consistent with the premise, that energetic abnormalities may contribute metabolically to SM weakness in this geriatric syndrome. PMID:23695949

Akki, Ashwin; Yang, Huanle; Gupta, Ashish; Chacko, Vadappuram P; Yano, Toshiyuki; Leppo, Michelle K; Steenbergen, Charles; Walston, Jeremy; Weiss, Robert G

2013-05-22

269

ATP Hydrolyzing Salivary Enzymes of Caterpillars Suppress Plant Defenses  

PubMed Central

The oral secretions of herbivores are important recognition cues that can be used by plants to mediate induced defenses. In this study, a degradation of adenosine-5?-triphosphate (ATP) in tomato leaves was detected after treatment with Helicoverpa zea saliva. Correspondingly, a high level of ATPase activity in saliva was detected and three ATP hydrolyzing enzymes: apyrase, ATP synthase and ATPase 13A1 were identified in salivary glands. To determine the functions of these proteins in mediating defenses, they were cloned from H. zea and expressed in Escherichia coli. By applying the purified expressed apyrase, ATP synthase or ATPase 13A1 to wounded tomato leaves, it was determined that these ATP hydrolyzing enzymes suppressed the defensive genes regulated by the jasmonic acid and ethylene pathways in tomato plant. Suppression of glandular trichome production was also observed after treatment. Blood-feeding arthropods employ 5?-nucleotidase family of apyrases to circumvent host responses and the H. zea apyrase, is also a member of this family. The comparatively high degree of sequence similarity of the H. zea salivary apyrase with mosquito apyrases suggests a broader evolutionary role for salivary apyrases than previously envisioned.

Wu, Shuang; Peiffer, Michelle; Luthe, Dawn S.; Felton, Gary W.

2012-01-01

270

ATP can be dispensable for prespliceosome formation in yeast  

PubMed Central

The first ATP-dependent step in pre-mRNA splicing involves the stable binding of U2 snRNP to form the prespliceosome. We show that a prespliceosome-like complex forms in the absence of ATP in yeast extracts lacking the U2 suppressor protein CUS2. These complexes display the same pre-mRNA and U snRNA requirements as authentic prespliceosomes and can be chased through the splicing pathway, indicating that they are a functional intermediate in the spliceosome assembly pathway. ATP-independent prespliceosome-like complexes are also observed in extracts containing a mutant U2 snRNA. Loss of CUS2 does not bypass the role of PRP5, an RNA helicase family member required for ATP-dependent prespliceosome formation. Genetic interactions between CUS2 and a heat-sensitive prp5 allele parallel those observed between CUS2 and U2, and suggest that CUS2 mediates functional interactions between U2 RNA and PRP5. We propose that CUS2 enforces ATP dependence during formation of the prespliceosome by brokering an interaction between PRP5 and the U2 snRNP that depends on correct U2 RNA structure.

Perriman, Rhonda; Ares, Manuel

2000-01-01

271

CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.  

PubMed

In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via ?(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel. PMID:21943397

Kanno, Takeshi; Nishizaki, Tomoyuki

2011-09-24

272

ATP-dependent looping of DNA by ISWI.  

PubMed

Snf2 related chromatin remodelling enzymes possess an ATPase subunit similar to that of the SF-II helicases which hydrolyzes ATP to track along DNA. Translocation and any resulting torque in the DNA could drive chromatin remodeling. To determine whether the ISWI protein can translocate and generate torque, tethered particle motion experiments and atomic force microscopy have been performed using recombinant ISWI expressed in E. coli. In the absence of ATP, ISWI bound to and wrapped DNA thereby shortening the overall contour length measured in atomic force micrographs. Although naked DNA only weakly stimulates ATP hydrolysis by ISWI, both atomic force microscopy and tethered particle motion data indicate that the protein generated loops in the presence of ATP. The duration of the looped state of the DNA measured using tethered particle motion was ATP-dependent. Finally, ISWI relaxed positively supercoiled plasmids visualized by atomic force microscopy. While other chromatin remodeling ATPases catalyze either DNA wrapping or looping, both are catalyzed by ISWI. PMID:19343651

Lia, Giuseppe; Indrieri, Marco; Owen-Hughes, Tom; Finzi, Laura; Podesta, Alessandro; Milani, Paolo; Dunlap, David

2008-09-01

273

ATP and ADP hydrolysis in cell membranes from rat myometrium.  

PubMed

Extracellular nucleotides affect female reproductive functions, fertilization, and pregnancy. The aim of this study was to investigate biochemical characteristics of ATP and ADP hydrolysis and identify E-NTPDases in myometrial cell membranes from Wistar albino rats. The apparent K (m) values were 506.4 ± 62.1 and 638.8 ± 31.3 ?M, with a calculated V (max) (app) of 3,973.0 ± 279.5 and 2,853.9 ± 79.8 nmol/min/mg for ATP and ADP, respectively. The enzyme activity described here has common properties characteristic for NTPDases: divalent cation dependence; alkaline pH optimum for both substrates, insensitivity to some of classical ATPase inhibitors (ouabain, oligomycine, theophylline, levamisole) and significant inhibition by suramine and high concentration of sodium azides (5 mM). According to similar apparent K(m) values for both substrates, the ATP/ADP hydrolysis ratio, and Chevillard competition plot, NTPDase1 is dominant ATP/ADP hydrolyzing enzyme in myometrial cell membranes. RT-PCR analysis revealed expression of three members of ectonucleoside triphosphate diphosphohydrolase family (NTPDase 1, 2, and 8) in rat uterus. These findings may further elucidate the role of NTPDases and ATP in reproductive physiology. PMID:22956447

Miloševi?, Maja; Petrovi?, Snježana; Veli?kovi?, Nataša; Grkovi?, Ivana; Ignjatovi?, Marija; Horvat, Anica

2012-09-07

274

Rotation and structure of FoF1-ATP synthase.  

PubMed

F(o)F(1)-ATP synthase is one of the most ubiquitous enzymes; it is found widely in the biological world, including the plasma membrane of bacteria, inner membrane of mitochondria and thylakoid membrane of chloroplasts. However, this enzyme has a unique mechanism of action: it is composed of two mechanical rotary motors, each driven by ATP hydrolysis or proton flux down the membrane potential of protons. The two molecular motors interconvert the chemical energy of ATP hydrolysis and proton electrochemical potential via the mechanical rotation of the rotary shaft. This unique energy transmission mechanism is not found in other biological systems. Although there are other similar man-made systems like hydroelectric generators, F(o)F(1)-ATP synthase operates on the nanometre scale and works with extremely high efficiency. Therefore, this enzyme has attracted significant attention in a wide variety of fields from bioenergetics and biophysics to chemistry, physics and nanoscience. This review summarizes the latest findings about the two motors of F(o)F(1)-ATP synthase as well as a brief historical background. PMID:21524994

Okuno, Daichi; Iino, Ryota; Noji, Hiroyuki

2011-04-26

275

ATP synthases: cellular nanomotors characterized by LILBID mass spectrometry  

PubMed Central

Mass spectrometry of membrane protein complexes is still a methodological challenge due to hydrophobic and hydrophilic parts of the species and the fact that all subunits are bound non-covalently together. The present study with the novel laser induced liquid bead ion desorption mass spectrometry (LILBID-MS) reports on the determination of the subunit composition of the F1Fo-ATP synthase from Bacillus pseudofirmus OF4, that of both bovine heart and, for the first time, of human heart mitochondrial F1Fo-ATP synthases. Under selected buffer conditions the mass of the intact F1Fo-ATP synthase of B. pseudofirmus OF4 could be measured, allowing the analysis of complex subunit stoichiometry. The agreement with theoretical masses derived from sequence databases is very good. A comparison of the ATP synthase subunit composition of 5 different ATPases reveals differences in the complexity of eukaryotic and bacterial ATP synthases. However, whereas the overall construction of eukaryotic enzymes is more complex than the bacterial ones, functionally important subunits are conserved among all ATPases.

Hoffmann, Jan; Sokolova, Lucie; Preiss, Laura; Hicks, David B.; Krulwich, Terry A.; Morgner, Nina; Wittig, Ilka; Schagger, Hermann; Meier, Thomas; Brutschy, Bernd

2010-01-01

276

ATP and AMP Mutually Influence Their Interaction with the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) at Separate Binding Sites.  

PubMed

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP-binding cassette (ABC) transporter protein family. In the presence of ATP and physiologically relevant concentrations of AMP, CFTR exhibits adenylate kinase activity (ATP + AMP &lrarr2; 2 ADP). Previous studies suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for this activity. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides. However, little is known about how an ABC adenylate kinase interacts with ATP and AMP when both are present. Based on data from non-ABC adenylate kinases, we hypothesized that ATP and AMP mutually influence their interaction with CFTR at separate binding sites. We further hypothesized that only one of the two CFTR ATP-binding sites is involved in the adenylate kinase reaction. We found that 8-azidoadenosine 5'-triphosphate (8-N3-ATP) and 8-azidoadenosine 5'-monophosphate (8-N3-AMP) photolabeled separate sites in CFTR. Labeling of the AMP-binding site with 8-N3-AMP required the presence of ATP. Conversely, AMP enhanced photolabeling with 8-N3-ATP at ATP-binding site 2. The adenylate kinase active center probe P(1),P(5)-di(adenosine-5') pentaphosphate interacted simultaneously with an AMP-binding site and ATP-binding site 2. These results show that ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. They further indicate that the active center of the adenylate kinase comprises ATP-binding site 2. PMID:23921386

Randak, Christoph O; Dong, Qian; Ver Heul, Amanda R; Elcock, Adrian H; Welsh, Michael J

2013-08-06

277

ATP and AMP Mutually Influence Their Interaction with the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) at Separate Binding Sites*  

PubMed Central

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP-binding cassette (ABC) transporter protein family. In the presence of ATP and physiologically relevant concentrations of AMP, CFTR exhibits adenylate kinase activity (ATP + AMP ? 2 ADP). Previous studies suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for this activity. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides. However, little is known about how an ABC adenylate kinase interacts with ATP and AMP when both are present. Based on data from non-ABC adenylate kinases, we hypothesized that ATP and AMP mutually influence their interaction with CFTR at separate binding sites. We further hypothesized that only one of the two CFTR ATP-binding sites is involved in the adenylate kinase reaction. We found that 8-azidoadenosine 5?-triphosphate (8-N3-ATP) and 8-azidoadenosine 5?-monophosphate (8-N3-AMP) photolabeled separate sites in CFTR. Labeling of the AMP-binding site with 8-N3-AMP required the presence of ATP. Conversely, AMP enhanced photolabeling with 8-N3-ATP at ATP-binding site 2. The adenylate kinase active center probe P1,P5-di(adenosine-5?) pentaphosphate interacted simultaneously with an AMP-binding site and ATP-binding site 2. These results show that ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. They further indicate that the active center of the adenylate kinase comprises ATP-binding site 2.

Randak, Christoph O.; Dong, Qian; Ver Heul, Amanda R.; Elcock, Adrian H.; Welsh, Michael J.

2013-01-01

278

Four mutations in transmembrane domains of the mitochondrial ADP/ATP carrier increase resistance to bongkrekic acid.  

PubMed

Two distinct conformations of the mitochondrial ADP/ATP carrier involved in the adenine nucleotide transport are called BA and CATR conformations, as they were distinguished by binding of specific inhibitors bongkrekic acid (BA) and carboxyatractyloside (CATR), respectively. To find out which amino acids are implicated in the transition between these two conformations, which occurs during transport, mutants of the Saccharomyces cerevisiae ADP/ATP carrier Anc2p responsible for resistance of yeast cells to BA were identified and characterized after in vivo chemical or UV mutagenesis. Only four different mutations could be identified in spite of a large number of mutants analyzed. They are located in the Anc2p transmembrane segments I (G30S), II (Y97C), III (L142S), and VI (G298S), and are independently enabling growth of cells in the presence of BA. The variant and wild-type Anc2p were produced practically to the same level in mitochondria, as evidenced by immunochemical analysis and by atractyloside binding experiments. ADP/ATP exchange mediated by Anc2p variants in isolated mitochondria was more efficient than that of the wild-type Anc2p in the presence of BA, confirming that BA resistance of the mutant cells was linked to the functional properties of the modified ADP/ATP carrier. These results suggest that resistance to BA is caused by alternate conformation of Anc2p due to appearance of Ser or Cys at specific positions. Different interactions of these residues with other amino acids and/or BA could prevent formation of stable inactive Anc2p . BA complex. PMID:13678275

Zeman, Igor; Schwimmer, Christine; Postis, Vincent; Brandolin, Gérard; David, Claudine; Trézéguet, Véronique; Lauquin, Guy J M

2003-06-01

279

ATP level and caffeine efficiency on cytokinesis inhibition in plants.  

PubMed

Plant cytokinesis appears to be a topographically organized process of exocytosis. Golgi vesicles which contain cell wall precursors are translocated during telophase, by interzonal microtubules, to the equatorial region of the mitotic apparatus where they fuse with each other giving rise to the new cell wall. Caffeine inhibits cytokinesis by hindering Golgi vesicle coalescence. The present results demonstrate that treatments which increase the cellular ATP level (adenosine, cycloheximide and anisomycin) counteract caffein-induced cytokinesis inhibition in meristem cells of onion root tips (Allium cepa L.), while treatments which decrease ATP level potentiate this caffeine effect (dinitrophenol, fluoroacetate, low oxygen tensions, etc.). We postulate that caffeine, in competition with the cellular ATP level, blocks cell plate formation by inhibiting a certain ATPase activity required for membrane fusion of Golgi vesicles. PMID:7117265

López-Sáez, J F; Mingo, R; González-Fernández, A

1982-06-01

280

Release of Adenosine and ATP During Ischemia and Epilepsy  

PubMed Central

Eighty years ago Drury & Szent-Györgyi described the actions of adenosine, AMP (adenylic acid) and ATP (pyrophosphoric or diphosphoric ester of adenylic acid) on the mammalian cardiovascular system, skeletal muscle, intestinal and urinary systems. Since then considerable insight has been gleaned on the means by which these compounds act, not least of which in the distinction between the two broad classes of their respective receptors, with their many subtypes, and the ensuing diversity in cellular consequences their activation invokes. These myriad actions are of course predicated on the release of the purines into the extracellular milieu, but, surprisingly, there is still considerable ambiguity as to how this occurs in various physiological and pathophysiological conditions. In this review we summarise the release of ATP and adenosine during seizures and cerebral ischemia and discuss mechanisms by which the purines adenosine and ATP may be released from cells in the CNS under these conditions.

Dale, Nicholas; Frenguelli, Bruno G

2009-01-01

281

Thermal activation and ATP dependence of the cytoskeleton remodeling dynamics  

NASA Astrophysics Data System (ADS)

The cytoskeleton (CSK) is a nonequilibrium polymer network that uses hydrolyzable sources of free energy such as adenosine triphosphate (ATP) to remodel its internal structure. As in inert nonequilibrium soft materials, CSK remodeling has been associated with structural rearrangements driven by energy-activated processes. We carry out particle tracking and traction microscopy measurements of alveolar epithelial cells at various temperatures and ATP concentrations. We provide the first experimental evidence that the remodeling dynamics of the CSK is driven by structural rearrangements over free-energy barriers induced by thermally activated forces mediated by ATP. The measured activation energy of these forces is ˜40kBTr ( kB being the Boltzmann constant and Tr being the room temperature). Our experiments provide clues to understand the analogy between the dynamics of the living CSK and that of inert nonequilibrium soft materials.

Sunyer, R.; Ritort, F.; Farré, R.; Navajas, D.

2009-05-01

282

Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K(+) channel currents by hypo-osmotic stress in rat ventricular myocytes.  

PubMed

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K(+) channel (KATP) openings by hypo-osmotic stress. The whole-cell KATP currents (IK,ATP) stimulated by 100 ?mol/L pinacidil, a K(+) channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and Emax value for pinacidil-activated IK,ATP (measured at 0 mV) was 154 ?mol/L and 844 pA, respectively, in normal solution and 16.6 ?mol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of IK,ATP during hypo-osmotic stress was attenuated by wortmannin (50 ?mol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 ?mol/L), an actin filament stabilizer, (ii) the absence of Ca(2+) from the internal and external solutions, and (iii) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the KATP channels. In the single-channel recordings, an inside-out patch was made after approximately 5 min exposure of the myocyte to hypo-osmotic solution. However, the IC50 value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiac IK,ATP through intracellular mechanisms involving the phosphatidylinositol kinase pathway. PMID:23984989

Mitsuyama, Hirofumi; Yokoshiki, Hisashi; Irie, Yuki; Watanabe, Masaya; Mizukami, Kazuya; Tsutsui, Hiroyuki

2013-03-05

283

ATP utilization by yeast replication factor C. I. ATP-mediated interaction with DNA and with proliferating cell nuclear antigen.  

PubMed

Eukaryotic replication factor C is the heteropentameric complex that loads the replication clamp proliferating cell nuclear antigen (PCNA) onto primed DNA. In this study we used a derivative, designated RFC, with a N-terminal truncation of the Rfc1 subunit removing a DNA-binding domain not required for clamp loading. Interactions of yeast RFC with PCNA and DNA were studied by surface plasmon resonance. Binding of RFC to PCNA was stimulated by either adenosine (3-thiotriphosphate) (ATPgammaS) or ATP. RFC bound only to primer-template DNA coated with the single-stranded DNA-binding protein RPA if ATPgammaS was also present. Binding occurred without dissociation of RPA. ATP did not stimulate binding of RFC to DNA, suggesting that hydrolysis of ATP dissociated DNA-bound RFC. However, when RFC and PCNA together were flowed across the DNA chip in the presence of ATP, a signal was observed suggesting loading of PCNA by RFC. With ATPgammaS present instead of ATP, long-lived response signals were observed indicative of loading complexes arrested on the DNA. A primer with a 3' single-stranded extension also allowed loading of PCNA; yet turnover of the reaction intermediates was dramatically slowed down. Filter binding experiments and analysis of proteins bound to DNA-magnetic beads confirmed the conclusions drawn from the surface plasmon resonance studies. PMID:11432853

Gomes, X V; Burgers, P M

2001-06-29

284

ATP-dependent remodeling of the spliceosome: intragenic suppressors of release-defective mutants of Saccharomyces cerevisiae Prp22.  

PubMed Central

The essential splicing factor Prp22 is a DEAH-box helicase that catalyzes the release of mRNA from the spliceosome. ATP hydrolysis by Prp22 is necessary but not sufficient for spliceosome disassembly. Previous work showed that mutations in motif III (635SAT637) of Prp22 that uncouple ATP hydrolysis from spliceosome disassembly lead to severe cold-sensitive (cs) growth defects and to impaired RNA unwinding activity in vitro. The cs phenotype of S635A (635AAT) can be suppressed by intragenic mutations that restore RNA unwinding. We now report the isolation and characterization of new intragenic mutations that suppress the cold-sensitive growth phenotypes of the T637A motif III mutation (SAA), the H606A mutation in the DEAH-box (DEAA), and the R805A mutation in motif VI (804QAKGRAGR811). Whereas the T637A and H606A proteins are deficient in releasing mRNA from the spliceosome at nonpermissive temperature in vitro, the suppressor proteins have recovered mRNA release activity. To address the mechanisms of suppression, we tested ATPase and helicase activities of Prp22 suppressor mutant proteins and found that the ability to unwind a 25-bp RNA duplex was not restored in every case. This finding suggests that release of mRNA from the spliceosome is less demanding than unwinding of a 25-bp duplex RNA; the latter reaction presumably reflects the result of several successive cycles of ATP binding, hydrolysis, and unwinding. Increasing the reaction temperature allows H606A and T637A to effect mRNA release in vitro, but does not restore RNA unwinding by T637A.

Campodonico, Eva; Schwer, Beate

2002-01-01

285

Molecular structure of the Menkes disease gene (ATP7A)  

SciTech Connect

We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene. 39 refs., 4 figs., 1 tab.

Dierick, H.A.; Glover, T.W. [Univ. of Michigan, Ann Arbor, MI (United States); Ambrosini, L. [Murdoch Institute, Victoria (Australia)] [and others

1995-08-10

286

Mechanism of ATP turnover inhibition in the EJC  

PubMed Central

The exon junction complex (EJC) is deposited onto spliced mRNAs and is involved in many aspects of mRNA function. We have recently reconstituted and solved the crystal structure of the EJC core made of MAGOH, Y14, the most conserved portion of MLN51, and the DEAD-box ATPase eIF4AIII bound to RNA in the presence of an ATP analog. The heterodimer MAGOH/Y14 inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA, but the exact mechanism behind this remains unclear. Here, we present the crystal structure of the EJC core bound to ADP-AIF3, the first structure of a DEAD-box helicase in the transition-mimicking state during ATP hydrolysis. It reveals a dissociative transition state geometry and suggests that the locking of the EJC onto the RNA by MAGOH/Y14 is not caused by preventing ATP hydrolysis. We further show that ATP can be hydrolyzed inside the EJC, demonstrating that MAGOH/Y14 acts by locking the conformation of the EJC, so that the release of inorganic phosphate, ADP, and RNA is prevented. Unifying features of ATP hydrolysis are revealed by comparison of our structure with the EJC–ADPNP structure and other helicases. The reconstitution of a transition state mimicking complex is not limited to the EJC and eIF4AIII as we were also able to reconstitute the complex Dbp5–RNA–ADP–AlF3, suggesting that the use of ADP–AlF3 may be a valuable tool for examining DEAD-box ATPases in general.

Nielsen, Klaus H.; Chamieh, Hala; Andersen, Christian B.F.; Fredslund, Folmer; Hamborg, Kristiane; Le Hir, Herve; Andersen, Gregers R.

2009-01-01

287

Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.  

PubMed Central

The alpha- and beta-subunits of membrane-bound ATP synthase complex bind ATP and ADP: beta contributes to catalytic sites, and alpha may be involved in regulation of ATP synthase activity. The sequences of beta-subunits are highly conserved in Escherichia coli and bovine mitochondria. Also alpha and beta are weakly homologous to each other throughout most of their amino acid sequences, suggesting that they have common functions in catalysis. Related sequences in both alpha and beta and in other enzymes that bind ATP or ADP in catalysis, notably myosin, phosphofructokinase, and adenylate kinase, help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.

Walker, J E; Saraste, M; Runswick, M J; Gay, N J

1982-01-01

288

In Vivo Fluorescent Adenosine 5'-Triphosphate (ATP) Imaging of Drosophila melanogaster and Caenorhabditis elegans by Using a Genetically Encoded Fluorescent ATP Biosensor Optimized for Low Temperatures.  

PubMed

Adenosine 5'-triphosphate (ATP) is the major energy currency of all living organisms. Despite its important functions, the spatiotemporal dynamics of ATP levels inside living multicellular organisms is unclear. In this study, we modified the genetically encoded Förster resonance energy transfer (FRET)-based ATP biosensor ATeam to optimize its affinity at low temperatures. This new biosensor, AT1.03NL, detected ATP changes inside Drosophila S2 cells more sensitively than the original biosensor did, at 25 °C. By expressing AT1.03NL in Drosophila melanogaster and Caenorhabditis elegans, we succeeded in imaging the in vivo ATP dynamics of these model animals at single-cell resolution. PMID:23875533

Tsuyama, Taiichi; Kishikawa, Jun-Ichi; Han, Yong-Woon; Harada, Yoshie; Tsubouchi, Asako; Noji, Hiroyuki; Kakizuka, Akira; Yokoyama, Ken; Uemura, Tadashi; Imamura, Hiromi

2013-08-08

289

Synthesis and in vitro characterization of a novel PAA-ATP conjugate.  

PubMed

The objective of this study was to improve the multifunctional properties of poly(acrylic acid) (PAA) by covalent attachment of 4-aminothiophenol (ATP) to its backbone. The permeation enhancing effect of PAA-ATP together with glutathione was evaluated in Ussing-type chambers using fluorescein isothiocyanate dextran as model compound. The mucoadhesive properties were evaluated in vitro on freshly excised porcine intestinal mucosa through the rotating cylinder method. The resulting conjugates PAA-ATP1 and PAA-ATP2 displayed 168 ± 35 and 426 ± 55 ?mol immobilized free thiol groups per gram polymer, respectively. In addition, 279 ± 28 and 139 ± 22 ?mol disulfide bonds per gram polymer, respectively, were identified on PAA-ATP1 and PAA-ATP2. Within disintegration studies in aqueous buffer solution, the modified polymers showed improved cohesive properties. Because of the immobilization of ATP, the swelling of PAA-ATP1 and PAA-ATP2 improved 12.0- and 17.8-fold, respectively. The adhesion times of the conjugates PAA-ATP1 and PAA-ATP2 were more than 20- and 30-fold increased in comparison to unmodified PAA. Furthermore, conjugates PAA-ATP1 and PAA-ATP2 exhibited a 1.86- and 2.07-fold higher permeation enhancing effect, respectively, over unmodified PAA. According to these results, PAA-ATP conjugates represent a very promising novel type of thiomer for the development of various mucoadhesive drug delivery systems. PMID:20923387

Hoyer, Herbert; Hombach, Juliane; Perera, Glen; Thaurer, Michael; Bernkop-Schnürch, Andreas

2010-10-06

290

Definitions: Communicative Disorders and Variations.  

ERIC Educational Resources Information Center

Definitions are provided for the overall category of "communicative disorder," and "hearing disorder." In addition, definitions are provided for the following narrower categories: "voice disorder,""articulation disorder,""fluency disorder,""deaf," and "hard of hearing." Journal Availability: See EC 152 480. (SEW)

Asha, 1982

1982-01-01

291

On some definitions of mindfulness  

Microsoft Academic Search

The Buddhist technical term was first translated as ‘mindfulness’ by T.W. Rhys Davids in 1881. Since then various authors, including Rhys Davids, have attempted definitions of what precisely is meant by mindfulness. Initially these were based on readings and interpretations of ancient Buddhist texts. Beginning in the 1950s some definitions of mindfulness became more informed by the actual practice of

Rupert Gethin

2011-01-01

292

Ostensive Definition in Vocabulary Teaching.  

ERIC Educational Resources Information Center

|Ostensive definitions of words are ambiguities as to their referent. In a study of infant-mother dyads engaged in looking at picture books, 95 percent of ostensive definitions referred to the whole object depicted rather than parts, attributes, or actions. When parts were named, ambiguity was avoided by naming the part and the whole. (PJM)|

Ninio, Anat

1980-01-01

293

Functional studies of ATP sulfurylase from Penicillium chrysogenum  

SciTech Connect

ATP sulfurylase from Penicillium chrysogenum has a specific activity (V/sub max/) of 6-7 units x mg protein/sup -1/ determined with the physiological substrates of MgATP and SO/sub 4//sup 2 -/ and assayed by (A) initial velocity measurements with APS kinase and inorganic pyrophosphatase present and (B) analysis of nonlinear reaction progress curves. The fact both assays give the same results show the intrinsic activity of ATP sulfurylase is much higher than previously reported. In initial velocity dead-end inhibition studies, the sulfate analog S/sub 2/O/sub 3//sup 2 -/ is a competitive inhibitor of SO/sub 42/..sqrt.. and a noncompetitive inhibitor of MgATP. Monovalent oxyanions such as NO/sub 3//sup -/, ClO/sub 3//sup -/, ClO/sub 4//sup -/, and FSO/sub 3//sup -/ behave as uncompetitive inhibitors of MgATP and thus seem not to be true sulfate analogs. The reverse reaction was assayed by the pyrophosphate dependent release of /sup 35/SO/sub 4//sup 2 -/ from AP/sup 35/S. Product inhibition by MgATP or SO/sub 4//sup 2 -/ is competitive with APS and mixed-type with PP/sub i/. Imidodiphosphate can serve as an alternative substrate for PP/sub i/. ATP sulfurylase binds (but does not hydrolyze) APS. A Scatchard plot of the APS binding is nonlinear, suggesting at least two types of sites. The cumulative results are qualitatively consistent with the random addition of MgATP and SO/sub 4//sup 2 -/ and the ordered release of first MgPP/sub i/ then APS, with APS release being partially rate limiting. Certain quantitative discrepancies suggest either an unknown variable (e.g. enzyme concentration) complicates the analysis or, in light of binding studies that the actual mechanism is more complicated (e.g. alternating sites) than any of the conventional models examined.

Seubert, P.A.

1985-01-01

294

Reliability of a bioluminescence ATP assay for detection of bacteria.  

PubMed Central

The reliability of bioluminescence assays which employ the luciferin-luciferase ATP-dependent reaction to evaluate bacterial counts was studied, both in vitro and on urine specimens. Bioluminescence and cultural results for the most common urinary tract pathogens were analyzed. Furthermore, the influence of the culture medium, of the assaying method, and of the phase of growth on bioluminescence readings was studied. Results show that Proteus, Providencia, and Morganella strains are not correctly detected, neither in vitro nor in urine samples, by the standard assaying method. The analysis of assaying parameters demonstrated that some modifications to the extraction procedure of bacterial ATP could improve the reliability of this technique.

Selan, L; Berlutti, F; Passariello, C; Thaller, M C; Renzini, G

1992-01-01

295

Reliability of a bioluminescence ATP assay for detection of bacteria.  

PubMed

The reliability of bioluminescence assays which employ the luciferin-luciferase ATP-dependent reaction to evaluate bacterial counts was studied, both in vitro and on urine specimens. Bioluminescence and cultural results for the most common urinary tract pathogens were analyzed. Furthermore, the influence of the culture medium, of the assaying method, and of the phase of growth on bioluminescence readings was studied. Results show that Proteus, Providencia, and Morganella strains are not correctly detected, neither in vitro nor in urine samples, by the standard assaying method. The analysis of assaying parameters demonstrated that some modifications to the extraction procedure of bacterial ATP could improve the reliability of this technique. PMID:1629329

Selan, L; Berlutti, F; Passariello, C; Thaller, M C; Renzini, G

1992-07-01

296

ATP-Sensitive K+ Channels: Paradigm Lost, Paradigm Regained  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. In an update of a previous Perspective [L. H. Philipson and D. F. Steiner, Science 268, 372 (1995)], Philipson discusses the molecular basis for Ksubscript ATP, a potassium current that mediates glucose regulation of insulin secretion. A prediction in the previous Perspective is borne out by a paper in this issue of Science (Inagaki et al., p. 1166), which reports the cloning of a new inward rectifier potassium channel and shows that Ksubscript ATP is formed when this channel combines with the sulfonylurea receptor.

Louis H. Philipson (University of Chicago;Department of Medicine and is on the Committee on Cell Physiology)

1995-11-17

297

Two distinct cytosolic calcium responses to extracellular ATP in rat parotid acinar cells.  

PubMed Central

1. Increasing concentrations of ATP (0.5 microM-300 microM) produced a biphasic increase in intracellular calcium concentration [Ca]i in rat parotid acinar cells, reflecting two distinct Cai responses to extracellular ATP. 2. In the absence of Mg2+ (with 3 mM CaCl2 in the buffer solution), the more sensitive response was maximal at 3-5 microM and was not further increased by 30 microM ATP. This response to ATP was not well maintained and was blocked by ADP (0.5 mM). A second, much larger increase in Cai was observed on addition of 300 microM ATP. This larger effect, which we have described previously, appears to be mediated by ATP4-, and was selectively reversed by 4,4'-di-isothiocyanato-dihydrostilbene-2,2'-disulphonate as well as by high concentrations of alpha,beta-methylene ATP. 3. Among ATP analogues, only the putative P2Z agonist, 3'-0-(4-benzoyl)benzoyl-ATP distinguished between the two responses. This analogue was at least 10 fold more potent than ATP in stimulating the ATP(4-)-response, but did not evoke the more sensitive response. The agonist potency series for both responses to ATP was identical for other analogues examined (ATP > ATP gamma S = 2-methylthio ATP (a P2y-selective agonist) >> ADP, ITP and alpha,beta-methylene ATP (a P2x-selective agonist)). 4. Although the effect of ATP4- could best be characterized as a P2z-type purinoceptor response, this effect was strongly and selectively blocked by reactive blue 2, a putative P2y-purinoceptor antagonist. Reactive blue 2 may bind to and block P2z purinoceptors since [gamma 32P]-ATP binding to parotid cells was inhibited by this compound.(ABSTRACT TRUNCATED AT 250 WORDS)

McMillian, M. K.; Soltoff, S. P.; Cantley, L. C.; Rudel, R.; Talamo, B. R.

1993-01-01

298

Iridium(III) azuliporphyrins.  

PubMed

Azuliporphyrins were reacted with [Ir(COD)Cl](2) in refluxing o- or p-xylene to give novel iridium(III) derivatives that regioselectively incorporated an oxidized solvent molecule. The iridium(III) is inserted within the porphyrinoid macrocycle and possesses an additional apical acyl unit. PMID:23111425

Lash, Timothy D; Pokharel, Komal; Zeller, Matthias; Ferrence, Gregory M

2012-10-31

299

Extracellular ATP signaling via P2X(4) receptor and cAMP/PKA signaling mediate ATP oscillations essential for prechondrogenic condensation.  

PubMed

Prechondrogenic condensation is the most critical process in skeletal patterning. A previous study demonstrated that ATP oscillations driven by Ca(2+) oscillations play a critical role in prechondrogenic condensation by inducing oscillatory secretion. However, it remains unknown what mechanisms initiate the Ca(2+)-driven ATP oscillations, mediate the link between Ca(2+) and ATP oscillations, and then result in oscillatory secretion in chondrogenesis. This study has shown that extracellular ATP signaling was required for both ATP oscillations and prechondrogenic condensation. Among P2 receptors, the P2X(4) receptor revealed the strongest expression level and mediated ATP oscillations in chondrogenesis. Moreover, blockage of P2X(4) activity abrogated not only chondrogenic differentiation but also prechondrogenic condensation. In addition, both ATP oscillations and secretion activity depended on cAMP/PKA signaling but not on K(ATP) channel activity and PKC or PKG signaling. This study proposes that Ca(2+)-driven ATP oscillations essential for prechondrogenic condensation is initiated by extracellular ATP signaling via P2X(4) receptor and is mediated by cAMP/PKA signaling and that cAMP/PKA signaling induces oscillatory secretion to underlie prechondrogenic condensation, in cooperation with Ca(2+) and ATP oscillations. PMID:22685336

Kwon, Hyuck Joon

2012-06-08

300

The hypertriglyceridemic waist phenotype versus the National Cholesterol Education Program–Adult Treatment Panel III and International Diabetes Federation clinical criteria to identify high-risk men with an altered cardiometabolic risk profile  

Microsoft Academic Search

The hypertriglyceridemic waist phenotype, the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATP III) criteria, and the International Diabetes Federation (IDF) criteria have been proposed as screening tools to identify subjects with features of the metabolic syndrome and therefore at increased cardiometabolic risk. The aim of the present study was to compare the ability of these 3 clinical approaches to

Patricia Blackburn; Isabelle Lemieux; Natalie Alméras; Jean Bergeron; Mélanie Côté; Angelo Tremblay; Benoît Lamarche; Jean-Pierre Després

2009-01-01

301

Mechanism for reactivation of the ATP-sensitive K+ channel by MgATP complexes in guinea-pig ventricular myocytes.  

PubMed Central

1. A mechanism underlying reactivation of the adenosine 5'-triphosphate-sensitive K+ (K+ATP) channels by MgATP complexes after run-down was examined in guinea-pig ventricular myocytes using the patch-clamp technique with inside-out patch configuration. 2. After run-down was induced by exposure of the intracellular side of the membrane patch to Ca2+ (1 mM), channel activity was reactivated by exposure and subsequent wash-out of MgATP (2 mM). Addition of inhibitors of various serine/threonine protein kinases to the MgATP solution did not suppress reactivation of the run-down channels. 3. Non- or poorly hydrolysable ATP analogues were unable to reactivate run-down channels. 4. The degree of channel recovery was dependent upon the duration of MgATP exposure. The apparent half-activation value (K1/2) of MgATP for reactivation was decreased with increasing exposure time. 5. Various products of ATP hydrolysis were unable to reactivate run-down channels except a relatively low concentration (100 microM) of ADP exposure. 6. Other nucleotide triphosphates, in the presence of Mg2+, were unable to reactivate rundown channels. 7. Fluorescein 5-isothiocyanate (50 microM), which interacts with lysine residues of the nucleotide-binding site on various ATPases, inhibited K+ATP channel activity. After wash-out, channel activity recovered only slightly. 8. These data suggest that the hydrolysis of ATP is important for reactivation of run-down K+ATP channels but that protein phosphorylation by serine/threonine protein kinases may not be involved. Since no products of ATP hydrolysis could reproduce MgATP-induced channel reactivation and since the degree of channel recovery was dependent upon the duration of MgATP application, the hydrolysis energy appears to be utilized for channel reactivation.

Furukawa, T; Virag, L; Furukawa, N; Sawanobori, T; Hiraoka, M

1994-01-01

302

Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis  

PubMed Central

The ability of glycolysis, oxidative phosphorylation, the creatine kinase system, and exogenous ATP to suppress ATP-sensitive K+ channels and prevent cell shortening were compared in patch-clamped single guinea pig ventricular myocytes. In cell-attached patches on myocytes permeabilized at one end with saponin, ATP-sensitive K+ channels were activated by removing ATP from the bath, and could be closed equally well by exogenous ATP or substrates for endogenous ATP production by glycolysis (with the mitochondrial inhibitor FCCP present), mitochondrial oxidative phosphorylation, or the creatine kinase system. In the presence of an exogenous ATP-consuming system, however, glycolytic substrates (with FCCP present) were superior to substrates for either oxidative phosphorylation or the creatine kinase system at suppressing ATP-sensitive K+ channels. All three groups of substrates were equally effective at preventing cell shortening. In 6 of 38 excised inside-out membrane patches, ATP-sensitive K+ channels activated by removing ATP from the bath were suppressed by a complete set of substrates for the ATP-producing steps of glycolysis but not by individual glycolytic substrates, which is consistent with the presence of key glycolytic enzymes located near the channels in these patches. Under whole-cell voltage-clamp conditions, inclusion of 15 mM ATP in the patch electrode solution dialyzing the interior of the cell did not prevent activation of the ATP-sensitive K+ current under control conditions or during exposure to complete metabolic inhibition. In isolated arterially perfused rabbit interventricular septa, selective inhibition of glycolysis caused an immediate increase in 42K+ efflux rate, which was prevented by 100 microM glyburide, a known blocker of ATP-sensitive K+ channels. These observations suggest that key glycolytic enzymes are associated with cardiac. ATP-sensitive K+ channels and under conditions in which intracellular competition for ATP is high (e.g., in beating heart) that act as a preferential source of ATP for these channels.

1989-01-01

303

Evidence that Na+/H+ exchanger 1 is an ATP-binding protein.  

PubMed

Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1. PMID:23331996

Shimada-Shimizu, Naoko; Hisamitsu, Takashi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

2013-02-15

304

High definition systems in Japan  

NASA Astrophysics Data System (ADS)

The successful implementation of a strategy to produce high-definition systems within the Japanese economy will favorably affect the fundamental competitiveness of Japan relative to the rest of the world. The development of an infrastructure necessary to support high-definition products and systems in that country involves major commitments of engineering resources, plants and equipment, educational programs and funding. The results of these efforts appear to affect virtually every aspect of the Japanese industrial complex. The results of assessments of the current progress of Japan toward the development of high-definition products and systems are presented. The assessments are based on the findings of a panel of U.S. experts made up of individuals from U.S. academia and industry, and derived from a study of the Japanese literature combined with visits to the primary relevant industrial laboratories and development agencies in Japan. Specific coverage includes an evaluation of progress in R&D for high-definition television (HDTV) displays that are evolving in Japan; high-definition standards and equipment development; Japanese intentions for the use of HDTV; economic evaluation of Japan's public policy initiatives in support of high-definition systems; management analysis of Japan's strategy of leverage with respect to high-definition products and systems.

Elkus, Richard J., Jr.; Cohen, Robert B.; Dayton, Birney D.; Messerschmitt, David G.; Schreiber, William F.; Tannas, Lawrence E., Jr.; Shelton, Duane

1991-02-01

305

A GLOBAL ATP COMPUTING SYSTEM FOR ORDER PROMISING  

Microsoft Academic Search

Providing realistic order promise dates or answering customer order quotation on a timely basis offers the key to fulfill customers demand for the growth of global customers. ATP (available-to-promise) is the uncommitted portion of stocks to support customer order promising. This order promising mechanism cannot reserve capacity and material resource for important customer in advance. Moreover, the assumptions of infinite

James T. Lin; Juin-Han Chen

306

ATP drives direct photosynthetic production of 1-butanol in cyanobacteria  

PubMed Central

While conservation of ATP is often a desirable trait for microbial production of chemicals, we demonstrate that additional consumption of ATP may be beneficial to drive product formation in a nonnatural pathway. Although production of 1-butanol by the fermentative coenzyme A (CoA)-dependent pathway using the reversal of ?-oxidation exists in nature and has been demonstrated in various organisms, the first step of the pathway, condensation of two molecules of acetyl-CoA to acetoacetyl-CoA, is thermodynamically unfavorable. Here, we show that artificially engineered ATP consumption through a pathway modification can drive this reaction forward and enables for the first time the direct photosynthetic production of 1-butanol from cyanobacteria Synechococcus elongatus PCC 7942. We further demonstrated that substitution of bifunctional aldehyde/alcohol dehydrogenase (AdhE2) with separate butyraldehyde dehydrogenase (Bldh) and NADPH-dependent alcohol dehydrogenase (YqhD) increased 1-butanol production by 4-fold. These results demonstrated the importance of ATP and cofactor driving forces as a design principle to alter metabolic flux.

Lan, Ethan I.; Liao, James C.

2012-01-01

307

[Suggested mitochondrial ancestry of non-mitochondrial ATP/ADP].  

PubMed

One of the major evolutionary events that transformed endosymbiotic bacterium into mitochondrion was an acquisition of ATP/ADP carrier in order to supply the host with respiration-derived ATP. Along with mitochondrial carrier, unrelated carrier is known which is characteristic of intracellular chlamydiae, plastids, parasitic intracellular eukaryote Encephalitozoon cuniculi, and the genus Rickettsia of obligate endosymbiotic alpha-Proteobacteria. This non-mitochondrial ATP/ADP carrier was recently described in rickettsia-like endosymbionts - a group of obligate intracellular bacteria, classified with the order Rickettsiales, which have diverged after free-living alpha-Proteobacteria but before sister groups of the Rickettsiaceae assemblage (true rickettsiae) and mitochondria. Published controversial phylogenetic data on the non-mitochondrial carrier were reanalysed in the present work using both DNA and protein sequences, and various methods including Bayesian analysis. The data presented are consistent with classic endosymbiont theory for the origin of mitochondria and also suggest that even last but one common ancestor of rickettsiae and organelles may have been an endosymbiotic bacterium in which ATP/ADP carrier has first originated. PMID:17380892

Emel'ianov, V V

308

An infrared fluorescent dATP for labeling DNA.  

PubMed

Near-infrared fluorescence provides a nonradioactive method of detection with high sensitivity and low background. An infrared fluorophore has been attached covalently to the nucleotide deoxyadenosine triphosphate (dATP) to provide a reagent for enzymatic labeling of various types of DNA molecules and for facilitating their detection with an automated DNA sequencing and analysis system. DNA sequencing reaction products can be labeled internally by performing limited polymerization utilizing infrared-labeled dATP (IR-dATP) as the sole source of adenine deoxynucleotide prior to a dideoxy-specific termination reaction. PCR products can be labeled fluorescently by the addition of limited quantities of IR-dATP to the amplification reaction. This latter strategy has been utilized for detection of short tandem repeat polymorphisms (STRPs) which are useful for gene mapping, genetic diagnostics, forensic analysis, and paternity testing. Restriction fragments can be labeled also by fill-in reactions of appropriate 5' overhangs. Diminutive amounts of such fluorescently labeled DNA molecules can be visualized rapidly and conveniently using infrared detection technology. PMID:8750198

Steffens, D L; Jang, G Y; Sutter, S L; Brumbaugh, J A; Middendorf, L R; Mühlegger, K; Mardis, E R; Weinstock, L A; Wilson, R K

1995-11-01

309

Teacher Development for ATP 2000. Project Report 1993-1994.  

ERIC Educational Resources Information Center

|Agri Tech Prep 2000 (ATP 2000) is a 4-year tech prep program intended to link high school and postsecondary curricula preparing New York students for careers in agriculture or acceptance into a college program in agriculture. Because teacher development was designated an integral project component for fiscal year 1992-93, a weeklong teacher…

Newsom-Stewart, Mhora; Sutphin, Dean

310

Teacher Development Program for ATP 2000. Project Report.  

ERIC Educational Resources Information Center

|Agri Tech Prep 2000 (ATP 2000) is a 4-year tech prep program linking high school and postsecondary curricula designed to prepare New York students for careers in agriculture or acceptance into a college program in agriculture. Because teacher development was designated an integral project component for fiscal year 1991-1992, a weeklong teacher…

Sutphin, Dean; And Others

311

ATP6V0D1/A0403  

NSDL National Science Digital Library

ATPase, proton-transporting, lysosomal V0 subunit D1 (ATP6V0D1, also known as A0403) is responsible for the acidification of endosomes, lysosomes, and other intracellular organelles in eukaryotic cells, thus providing most of the energy required for ...

2009-04-14

312

Cyclodextrin-based microcapsules as bioreactors for ATP biosynthesis.  

PubMed

A biomimetic energy converter was fabricated via the assembly of CF0F1-ATPase on lipid-coated hollow nanocapsules composed of ?-cyclodextrins/chitosan-graft-poly(ethylene glycol) methacrylate. Upon entrapped GOD into these capsules, the addition of glucose could trigger proton-motive force and then drive the rotation of ATPase to synthesize ATP. PMID:23962233

Li, Jian-Hu; Wang, Yi-Fu; Ha, Wei; Liu, Yan; Ding, Li-Sheng; Li, Bang-Jing; Zhang, Sheng

2013-08-26

313

Abiogenic Photophosphorylation of ADP to ATP Sensitized by Flavoproteinoid Microspheres  

NASA Astrophysics Data System (ADS)

A model for abiogenic photophosphorylation of ADP by orthophosphate to yield ATP was studied. The model is based on the photochemical activity of flavoproteinoid microspheres that are formed by aggregation in an aqueous medium of products of thermal condensation of a glutamic acid, glycine and lysine mixture (8:3:1) and contain, along with amino acid polymers (proteinoids), abiogenic isoalloxazine (flavin) pigments. Irradiation of aqueous suspensions of microspheres with blue visible light or ultraviolet in the presence of ADP and orthophosphate resulted in ATP formation. The yield of ATP in aerated suspensions was 10 20% per one mol of starting ADP. Deaeration reduced the photophosphorylating activity of microspheres five to 10 times. Treatment of aerated microsphere suspensions with superoxide dismutase during irradiation partially suppressed ATP formation. Deaerated microspheres restored completely their photophosphorylating activity after addition of hydrogen peroxide to the suspension. The photophosphorylating activity of deaerated suspensions of flavoproteinoid microspheres was also recovered by introduction of Fe3+-cytochrome c, an electron acceptor alternative to oxygen. On the basis of the results obtained, a chemical mechanism of phosphorylation is proposed in which the free radical form of reduced flavin sensitizer left( {{text{FlH}}^ bullet } right) and ADP are involved.

Kolesnikov, Michael P.; Telegina, Taisiya A.; Lyudnikova, Tamara A.; Kritsky, Mikhail S.

2008-06-01

314

ULTRASTRUCTURE OF ISOLATED KIDNEY MITOCHONDRIA TREATED WITH PHLORIZIN AND ATP  

Microsoft Academic Search

Direct electron microscopic evidence is reported of the ultrastructure of mitochondrial membranes and compartments in mitochondria isolated in 0.5 M sucrose from the rat kid- ney cortex and the experimental changes they undergo with phlorizin and ATP treatment. A heterogeneous population of mitochondria is recognized under control conditions. The mitochondria appear to be of 3 main types, normal, swollen, and

MARIO H. BURGOS; AGUSTIN AOKI; FABIO L. SACERDOTE

1964-01-01

315

Detection of ATP and NADH: A Bioluminescent Experience.  

ERIC Educational Resources Information Center

Described is a bioluminescent assay for adenosine triphosphate (ATP) and reduced nicotineamide-adenine dinucleotide (NADH) that meets the requirements of an undergraduate biochemistry laboratory course. The 3-hour experiment provides students with experience in bioluminescence and analytical biochemistry yet requires limited instrumentation,…

Selig, Ted C.; And Others

1984-01-01

316

The Human ATP-Binding Cassette (ABC) Transporter Superfamily  

Microsoft Academic Search

The ATP-binding cassette (ABC) transporter superfamily contains membrane proteins that translocate a wide variety of substrates across extra- and intracellular membranes, including metabolic products, lipids and sterols, and drugs. Overexpression of certain ABC transporters occurs in cancer cell lines and tumors that are multidrug resistant. Genetic variation in these genes is the cause or contributor to a wide variety of

Michael Dean; Andrey Rzhetsky; Rando Allikmets

2001-01-01

317

Teacher Development for ATP 2000. Project Report 1993-1994.  

ERIC Educational Resources Information Center

Agri Tech Prep 2000 (ATP 2000) is a 4-year tech prep program intended to link high school and postsecondary curricula preparing New York students for careers in agriculture or acceptance into a college program in agriculture. Because teacher development was designated an integral project component for fiscal year 1992-93, a weeklong teacher…

Newsom-Stewart, Mhora; Sutphin, Dean

318

The Algebra of Timed Processes, ATP: Theory and Application  

Microsoft Academic Search

We study a process algebra ATP for the description and analysis of systems of timedprocesses. An important feature of the algebra is that its vocabulary of actions contains adistinguished element . An occurrence of is a time event representing progress of time.The algebra has, apart from standard operators of process algebras like CCS or ACP, aprimitive binary unit-delay operator. For

Xavier Nicollin; Joseph Sifakis

1994-01-01

319

Rapid and precise determination of ATP using a modified photometer  

USGS Publications Warehouse

An inexpensive delay timer was designed to modify a commercially available ATP photometer which allows a disposable tip pipette to be used for injecting either enzyme or sample into the reaction cuvette. The disposable tip pipette is as precise and accurate as a fixed-needle syringe but eliminates the problem of sample contamination and decreases analytical time. (USGS)

Shultz, David J.; Stephens, Doyle W.

1980-01-01

320

Teacher Development Program for ATP 2000. Project Report.  

ERIC Educational Resources Information Center

Agri Tech Prep 2000 (ATP 2000) is a 4-year tech prep program linking high school and postsecondary curricula designed to prepare New York students for careers in agriculture or acceptance into a college program in agriculture. Because teacher development was designated an integral project component for fiscal year 1991-1992, a weeklong teacher…

Sutphin, Dean; And Others

321

ATP Production in Chlamydomonas reinhardtii Flagella by Glycolytic Enzymes  

Microsoft Academic Search

reinhardtii flagellum that catalyze three steps of the lower half of glycolysis (phosphoglycerate mutase, enolase, and pyruvate kinase). These enzymes can generate one ATP molecule for every substrate molecule consumed. Flagellar fractionation shows that enolase is at least partially associated with the axoneme, whereas phosphoglycerate mutase and pyruvate kinase primarily reside in the detergent-soluble (membrane matrix) compartments. We further show

Beth F. Mitchell; Lotte B. Pedersen; Michael Feely; Joel L. Rosenbaum

2005-01-01

322

The human ATP-binding cassette (ABC) transporter superfamily  

Microsoft Academic Search

The transport of specific molecules across lipid membranes is an essential function of all living organisms and a large number of specific transporters have evolved to carry out this function. The largest transporter gene family is the ATP-binding cassette (ABC) transporter superfamily. These proteins translocate a wide variety of substrates including sugars, amino acids, metal ions, peptides, and proteins, and

Michael Dean; Yannick Hamon; Giovanna Chimini

2001-01-01

323

ATP-dependent assembly of the human origin recognition complex.  

PubMed

The origin recognition complex (ORC) was initially discovered in budding yeast extracts as a protein complex that binds with high affinity to autonomously replicating sequences in an ATP-dependent manner. We have cloned and expressed the human homologs of the ORC subunits as recombinant proteins. In contrast to other eukaryotic initiators examined thus far, assembly of human ORC in vitro is dependent on ATP binding. Mutations in the ATP-binding sites of Orc4 or Orc5 impair complex assembly, whereas Orc1 ATP binding is not required. Immunofluorescence staining of human cells with anti-Orc3 antibodies demonstrate cell cycle-dependent association with a nuclear structure. Immunoprecipitation experiments show that ORC disassembles as cells progress through S phase. The Orc6 protein binds directly to the Orc3 subunit and interacts as part of ORC in vivo. These data suggest that the assembly and disassembly of ORC in human cells is uniquely regulated and may contribute to restricting DNA replication to once in every cell division cycle. PMID:17716973

Siddiqui, Khalid; Stillman, Bruce

2007-08-22

324

Developmental aspects of amperometric ATP biosensors based on entrapped enzymes.  

PubMed

A novel concept for a dual-enzyme-based microbiosensor for the detection of adenosine-5'-triphosphate (ATP) was developed. The employed enzymes pyrroloquinoline quinone-dependent glucose dehydrogenase (PQQ-GDH) and hexokinase were entrapped, using pH-shift-induced precipitation of electrodeposition paint (EDP) at platinum microelectrodes (diameter of 25 microm). PQQ-GDH is known showing a superior activity for glucose conversion at the relevant conditions (low oxygen concentration) for ATP detection in targeted biomedical studies. For immobilizing the two enzymes PQQ-GDH and hexokinase, the deposition conditions of EDP Resydrol AY498w/35WA were adapted to ensure high immobilization rates. Prior to ATP sensing, the conversion of glucose, which is the co-substrate for both enzymatic reactions, was optimized. Optimization was targeted towards ATP measurements in biomedical environments by optimizing the PQQ-GDH sensor for glucose. Therefore, different mediators were tested regarding their electron transfer rate and their compatibility with the enzyme: free-diffusing N-methylphenazonium methyl sulfate (PMS) and ferrocenemethanol, and an immobilized chromium hexacyanoferrate layer at platinum electrode. Free-diffusing ferrocenemethanol reveals high sensitivity towards glucose of 1.5 +/- 0.4 nA/mM. In a next step, hexokinase was co-entrapped in the polymer film resulting in a sensitivity of up to 290 pA/microM. PMID:19779927

Weber, Cornelia; Gauda, Estelle; Mizaikoff, Boris; Kranz, Christine

2009-11-01

325

Human myocardial ATP content and in vivo contractile function  

Microsoft Academic Search

The study was designed to characterize the relationship between the metabolise content of human cardiac muscle and in vivo cardiac function. ATP, total adenine nucleotides, and NAD were quantified in human myocardial biopsies using high performance liquid chromatography. Right ventricular endomyocardial biopsies were obtained from 43 patients with dilated cardiomyopathy, 6 with restrictive cardiomyopathy, 10 with normal systolic and diastolic

Randall C. Starling; Donald F. Hammer; Ruth A. Altschuld

1998-01-01

326

Detection of ATP and NADH: A Bioluminescent Experience.  

ERIC Educational Resources Information Center

|Described is a bioluminescent assay for adenosine triphosphate (ATP) and reduced nicotineamide-adenine dinucleotide (NADH) that meets the requirements of an undergraduate biochemistry laboratory course. The 3-hour experiment provides students with experience in bioluminescence and analytical biochemistry yet requires limited instrumentation,…

Selig, Ted C.; And Others

1984-01-01

327

Compartmentation of ATP:Citrate Lyase in Plants1  

Microsoft Academic Search

Extracts prepared from young leaves of Pea (Pisum sativum), tobacco (Nicotiana tabacum), rape (Brassica napus), and spinach (Spinacia oleracea) all contained ATP:citrate lyase (ACL) activity, which was most active in rape leaflets (130 nmol min21 g fresh weight). In rape and spinach, ACL activity was predominantly lo- calized in the plastids (between about 78% and 90% of the total activity),

Dhandapani Rangasamy; Colin Ratledge

2000-01-01

328

Distinct Wilson-disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B  

PubMed Central

Background/Aims Wilson disease is characterized by hepatic copper overload and caused by mutations in the gene encoding the copper transporting P-type ATPase ATP7B. ATP7B interacts with COMMD1, a protein that is deleted in Bedlington terriers with hereditary copper toxicosis. Here we characterized the implications of the interaction between COMMD1 and ATP7B in relation to the pathogenesis of Wilson disease. Methods GST pull-down experiments, co-immunoprecipitations, immunofluoresensce microscopy, site-directed mutagenesis and biosynthetic labeling experiments were performed to characterize the interaction between COMMD1 and ATP7B and the effects of Wilson disease causing mutations. Results COMMD1 specifically interacted with the amino-terminal region of ATP7B. This interaction was independent of intracellular copper levels and of the expression of the copper chaperone ATOX1. Four Wilson disease patient derived mutations in this region of ATP7B significantly increased its binding to COMMD1. Two of these mutations also resulted in mislocalization and increased degradation rate of ATP7B. Although COMMD1 did not affect copper-induced trafficking of ATP7B, it markedly decreased the stability of newly synthesized ATP7B. Conclusions Our data implicate COMMD1 in the pathogenesis of Wilson disease and indicate that COMMD1 exerts its regulatory role in copper homeostasis through the regulation of ATP7B stability.

de Bie, Prim; van de Sluis, Bart; Burstein, Ezra; van de Berghe, Peter V.E.; Muller, Patricia; Berger, Ruud; Gitlin, Jonathan D.; Wijmenga, Cisca; Klomp, Leo W.J.

2008-01-01

329

24 CFR 902.3 - Definitions.  

Code of Federal Regulations, 2013 CFR

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2013-04-01

330

21 CFR 514.3 - Definitions.  

Code of Federal Regulations, 2010 CFR

...General Provisions § 514.3 Definitions. The definition and interpretation of terms...For example, under this definition hepatic necrosis would be unexpected...referred only to elevated hepatic enzymes or hepatitis. [68 FR...

2009-04-01

331

48 CFR 2002.100 - Definitions.  

Code of Federal Regulations, 2011 CFR

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2011-10-01

332

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Code of Federal Regulations, 2012 CFR

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2012-10-01

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Code of Federal Regulations, 2010 CFR

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2010-01-01

334

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Code of Federal Regulations, 2013 CFR

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2013-01-01

335

40 CFR 90.1002 - Definitions.  

Code of Federal Regulations, 2012 CFR

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2012-07-01

336

40 CFR 94.1102 - Definitions.  

Code of Federal Regulations, 2012 CFR

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2012-07-01

337

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Code of Federal Regulations, 2012 CFR

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2012-07-01

338

40 CFR 90.402 - Definitions.  

Code of Federal Regulations, 2012 CFR

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2012-07-01

339

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Code of Federal Regulations, 2012 CFR

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2012-07-01

340

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Code of Federal Regulations, 2010 CFR

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2010-07-01

341

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Code of Federal Regulations, 2012 CFR

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2012-10-01

342

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Code of Federal Regulations, 2011 CFR

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2011-07-01

343

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Code of Federal Regulations, 2011 CFR

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2011-10-01

344

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Code of Federal Regulations, 2011 CFR

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2011-10-01

345

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Code of Federal Regulations, 2012 CFR

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2012-10-01

346

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Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Definitions. 762.22 Section 762.22 Postal Service UNITED STATES POSTAL SERVICE...and Processing of Disbursement Postal Money Orders § 762.22 Definitions. For definitions applicable to...

2013-07-01

347

7 CFR 4280.103 - Definitions.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Definitions. 4280.103 Section...Program § 4280.103 Definitions. Terms used...the operations. Anaerobic digester project...except guarantors. Capacity. The maximum load...utilities meet SBA's definition of small...

2010-01-01

348

Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss  

PubMed Central

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the renal ?-intercalated cell's apical H+-ATPase that cause rdRTA. Defects in the B1 subunit gene ATP6V1B1, and the a4 subunit gene ATP6V0A4, cause rdRTA with deafness and with preserved hearing, respectively. We have investigated 26 new rdRTA kindreds, of which 23 are consanguineous. Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity. In ATP6V1B1, one novel and five previously reported mutations were found in 10 kindreds. In 12 ATP6V0A4 kindreds, seven of 10 mutations were novel. A further nine novel ATP6V0A4 mutations were found in "sporadic" cases. The previously reported association between ATP6V1B1 defects and severe hearing loss in childhood was maintained. However, several patients with ATP6V0A4 mutations have developed hearing loss, usually in young adulthood. We show here that ATP6V0A4 is expressed within the human inner ear. These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time.

Stover, E; Borthwick, K; Bavalia, C; Eady, N; Fritz, D; Rungroj, N; Giersch, A; Morton, C; Axon, P; Akil, I; Al-Sabban, E; Baguley, D; Bianca, S; Bakkaloglu, A; Bircan, Z; Chauveau, D; Clermont, M; Guala, A; Hulton, S; Kroes, H; Li, V; Mir, S; Mocan, H; Nayir, A; Ozen, S; Rodriguez, S; Sanjad, S; Tasic, V; Taylor, C; Topaloglu, R; Smith, A; Karet, F

2002-01-01

349

Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss.  

PubMed

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA. Defects in the B1 subunit gene ATP6V1B1, and the a4 subunit gene ATP6V0A4, cause rdRTA with deafness and with preserved hearing, respectively. We have investigated 26 new rdRTA kindreds, of which 23 are consanguineous. Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity. In ATP6V1B1, one novel and five previously reported mutations were found in 10 kindreds. In 12 ATP6V0A4 kindreds, seven of 10 mutations were novel. A further nine novel ATP6V0A4 mutations were found in "sporadic" cases. The previously reported association between ATP6V1B1 defects and severe hearing loss in childhood was maintained. However, several patients with ATP6V0A4 mutations have developed hearing loss, usually in young adulthood. We show here that ATP6V0A4 is expressed within the human inner ear. These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time. PMID:12414817

Stover, E H; Borthwick, K J; Bavalia, C; Eady, N; Fritz, D M; Rungroj, N; Giersch, A B S; Morton, C C; Axon, P R; Akil, I; Al-Sabban, E A; Baguley, D M; Bianca, S; Bakkaloglu, A; Bircan, Z; Chauveau, D; Clermont, M-J; Guala, A; Hulton, S A; Kroes, H; Li Volti, G; Mir, S; Mocan, H; Nayir, A; Ozen, S; Rodriguez Soriano, J; Sanjad, S A; Tasic, V; Taylor, C M; Topaloglu, R; Smith, A N; Karet, F E

2002-11-01

350

The cotton ATP synthase ?1 subunit is required to maintain a higher ATP/ADP ratio that facilitates rapid fibre cell elongation.  

PubMed

The ? subunit of mitochondrial ATP synthase serves as a linker between the F(0) and F(1) sectors. Here, through microarray and quantitative RT-PCR, we found that the ?1 subunit was significantly up-regulated during cotton fibre cell elongation. Both the relative level and duration of GhATP?1 transcripts correlated positively with the final length of different cotton germplasms. Elongating fibre cells had a significantly elevated ATP/ADP ratio, suggesting that a higher energy input is probably required for primary fibre cell wall formation and elongation. We obtained a putative full-length GhATP?1 cDNA that shows 37% sequence identity to the Saccharomyces cerevisiae ATP16 at the deduced amino acid level. An almost wild-type growth rate was restored in atp16? cells that expressed GhATP?1, with a resultant ATP/ADP ratio similar to that found in wild-type cells, indicating that the cotton gene was functional in yeast. Mitochondria prepared from 10 dpa wild-type fibre cells showed significantly higher ATP synthase activity in comparison to ovule samples from wild type and leaf samples. Exogenous application of piceatannol (PA) or oligomycin (OM), inhibitors of ATP synthase F(1) or F(0) subunits, respectively, in ovule culture media resulted in much shorter fibre cells and a significantly lower ATP/ADP ratio. Our data suggest that GhATP?1 is important for activity of mitochondrial ATP synthase and is probably related to cotton fibre elongation. PMID:21040305

Pang, Y; Wang, H; Song, W-Q; Zhu, Y-X

2010-11-01

351

Activation of ATP binding for the autophosphorylation of DosS, a Mycobacterium tuberculosis histidine kinase lacking an ATP lid motif.  

PubMed

The sensor histidine kinases of Mycobacterium tuberculosis, DosS and DosT, are responsible for sensing hypoxic conditions and consist of sensor and kinase cores responsible for accepting signals and phosphorylation activity, respectively. The kinase core contains a dimerization and histidine phosphate-accepting (DHp) domain and an ATP binding domain (ABD). The 13 histidine kinase genes of M. tuberculosis can be grouped based on the presence or absence of the ATP lid motif and F box (elements known to play roles in ATP binding) in their ABDs; DosS and DosT have ABDs lacking both these elements, and the crystal structures of their ABDs indicated that they were unsuitable for ATP binding, as a short loop covers the putative ATP binding site. Although the ABD alone cannot bind ATP, the kinase core is functional in autophosphorylation. Appropriate spatial arrangement of the ABD and DHp domain within the kinase core is required for both autophosphorylation and ATP binding. An ionic interaction between Arg(440) in the DHp domain and Glu(537) in the short loop of the ABD is available and may open the ATP binding site, by repositioning the short loop away from the site. Mutations at Arg(440) and Glu(537) reduce autophosphorylation activity. Unlike other histidine kinases containing an ATP lid, which protects bound ATP, DosS is unable to accept ATP until the ABD is properly positioned relative to the histidine; this may prevent unexpected ATP reactions. ATP binding can, therefore, function as a control mechanism for histidine kinase activity. PMID:23486471

Cho, Ha Yeon; Lee, Young-Hoon; Bae, Young-Seuk; Kim, Eungbin; Kang, Beom Sik

2013-03-13

352

ATP hydrolysis coupled to microtubule sliding in sea-urchin sperm flagella.  

PubMed

Using sea urchin (Hemicentrotus pulcherimus) sperm flagella, ATP hydrolysis coupled to sliding movement of microtubules was investigated. Flagellar axonemes were pretreated with trypsin and the microtubules induced to slide by addition of ATP (50-1,000 microM) at 0-20 degrees C. Motion-dependent hydrolysis of ATP was observed immediately after the addition of ATP, the rate of which was higher than that of steady state hydrolysis in axonemes without trypsin-treatment, or after complete disintegration. The rate of hydrolysis of ATP divided by the sliding velocity of microtubules reflects the ATP consumption necessary per unit distance of microtubule sliding. This parameter varied according to the experimental conditions in that it increased when the ATP concentration or temperature was decreased. Our results suggest that there is not a strict stoichiometric relationship between ATP hydrolysis and sliding distance in the dynein-tubulin system, indicating that the mechanochemical coupling is different from that in beating axonemes. PMID:4030735

Kamimura, S; Yano, M; Shimizu, H

1985-05-01

353

Application of Firefly Luciferase Assay for Adenosine Triphosphate (ATP) to Antimicrobial Drug Sensitivity Testing.  

National Technical Information Service (NTIS)

The development of a rapid method for determining microbial susceptibilities to antibiotics using the firefly luciferase assay for adenosine triphosphate (ATP) is documented. The reduction of bacterial ATP by an antimicrobial agent was determined to be a ...

G. L. Picciolo S. Tuttle C. G. Schrock J. W. Deming M. Barza

1977-01-01

354

Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes  

PubMed Central

Erythrocytes release ATP in response to exposure to the physiological stimulus of lowered oxygen (O2) tension as well as pharmacological activation of the prostacyclin receptor (IPR). ATP release in response to these stimuli requires activation of adenylyl cyclase, accumulation of cAMP, and activation of protein kinase A. The mechanism by which ATP, a highly charged anion, exits the erythrocyte in response to lowered O2 tension or receptor-mediated IPR activation by iloprost is unknown. It was demonstrated previously that inhibiting pannexin 1 with carbenoxolone inhibits hypotonically induced ATP release from human erythrocytes. Here we demonstrate that three structurally dissimilar compounds known to inhibit pannexin 1 prevent ATP release in response to lowered O2 tension but not to iloprost-induced ATP release. These results suggest that pannexin 1 is the conduit for ATP release from erythrocytes in response to lowered O2 tension. However, the identity of the conduit for iloprost-induced ATP release remains unknown.

Adderley, Shaquria P.; Bowles, Elizabeth A.; Egan, Terrance M.; Stephenson, Alan H.; Ellsworth, Mary L.; Sprague, Randy S.

2010-01-01

355

'Depletion' of ATP by 2Deoxyglucose: Secretion by Electroporated Human Neutrophils Is Not Restored by Readdition of ATP  

Microsoft Academic Search

Studies of intracellular signal transduction are facilitated by the use of permeabilized cell systems, which permit the ready manipulation of the cytosol. These model systems have helped to define the roles that small solutes, particularly Ca2+ and nucleotides, play in stimulus-response coupling. In circumstances where the full depletion of intracellular ATP contents is required, some investigators have resorted to prior

James E. Smolen; Barbara Kuczynski; Eun Kyu Koh; Kenneth J. Balazovich; Alan Woronoff

1992-01-01

356

Structural models of the human copper P-type ATPases ATP7A and ATP7B.  

PubMed

The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B related to Menkes and Wilson diseases, respectively, structural information has only been available for isolated, soluble domains. Here we present homology models based on the existing structures of soluble domains and the recently determined structure of the homologous LpCopA from the bacterium Legionella pneumophila. The models and sequence analyses show that the domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved. In addition, there are only minor differences in the core structures of the two human proteins and the bacterial template, allowing protein-specific properties to be addressed. Furthermore, the mapping of known disease-causing missense mutations indicates that among the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, thus mimicking the single or dual HMBDs found in most copper-specific P-type ATPases. We propose a structural arrangement of the HMBDs and how they may interact with the core of the proteins to achieve autoinhibition. PMID:23029640

Gourdon, Pontus; Sitsel, Oleg; Lykkegaard Karlsen, Jesper; Birk Møller, Lisbeth; Nissen, Poul

2012-04-01

357

Reactive oxygen species affect ATP hydrolysis by targeting a highly conserved amino acid cluster in the thylakoid ATP synthase ? subunit.  

PubMed

The vast majority of organisms produce ATP by a membrane-bound rotating protein complex, termed F-ATP synthase. In chloroplasts, the corresponding enzyme generates ATP by using a transmembrane proton gradient generated during photosynthesis, a process releasing high amounts of molecular oxygen as a natural byproduct. Due to its chemical properties, oxygen can be reduced incompletely which generates several highly reactive oxygen species (ROS) that are able to oxidize a broad range of biomolecules. In extension to previous studies it could be shown that ROS dramatically decreased ATP synthesis in situ and affected the CF1 portion in vitro. A conserved cluster of three methionines and a cysteine on the chloroplast ? subunit could be identified by mass spectrometry to be oxidized by ROS. Analysis of amino acid substitutions in a hybrid F1 assembly system indicated that these residues were exclusive catalytic targets for hydrogen peroxide and singlet oxygen, although it could be deduced that additional unknown amino acid targets might be involved in the latter reaction. The cluster was tightly integrated in catalytic turnover since mutants varied in MgATPase rates, stimulation by sulfite and chloroplast-specific ? subunit redox-modulation. Some partial disruptions of the cluster by mutagenesis were dominant over others regarding their effects on catalysis and response to ROS. PMID:22727877

Buchert, Felix; Schober, Yvonne; Römpp, Andreas; Richter, Mark L; Forreiter, Christoph

2012-06-19

358

Disreputable science: definition and detection.  

PubMed

This paper describes definitions of fraud and misconduct as disreputable science. Some causes and methods of detection of scientific misconduct are identified. These hallmarks of credibility are essential for nursing to advance as a science. PMID:2229687

Morrison, R S

1990-08-01

359

ERDA Photovoltaic Systems Definition Project.  

National Technical Information Service (NTIS)

The ERDA Photovoltaic Systems Definition Project is aimed at identifying the most promising applications for terrestrial photovoltaic power systems and optimizing their reliability and cost-effectiveness. Various system concepts and candidate applications...

D. G. Schueler

1976-01-01

360

A Sample of Sampling Definitions.  

ERIC Educational Resources Information Center

|Describes a study examing 34 introductory psychological statistics texts for their usage and definitions of the terms "random sample" and "simple random sampling." Results showed a high percentage of conceptual errors. (CK)|

Bobko, Philip; And Others

1980-01-01

361

Evidence for sustained ATP release from liver cells that is not mediated by vesicular exocytosis  

Microsoft Academic Search

Extracellular ATP regulates many important cellular functions in the liver by stimulating purinergic receptors. Recent studies\\u000a have shown that rapid exocytosis of ATP-enriched vesicles contributes to ATP release from liver cells. However, this rapid\\u000a ATP release is transient, and ceases in ~30 s after the exposure to hypotonic solution. The purpose of these studies was to\\u000a assess the role of vesicular

Svjetlana Dolovcak; Shar L. Waldrop; Feng Xiao; Gordan Kilic

362

Mechanical effects of muscle contraction increase intravascular ATP draining quiescent and active skeletal muscle in humans.  

PubMed

Intravascular adenosine triphosphate (ATP) evokes vasodilation and is implicated in the regulation of skeletal muscle blood flow during exercise. Mechanical stresses to erythrocytes and endothelial cells stimulate ATP release in vitro. How mechanical effects of muscle contractions contribute to increased plasma ATP during exercise is largely unexplored. We tested the hypothesis that simulated mechanical effects of muscle contractions increase [ATP](venous) and ATP effluent in vivo, independent of changes in tissue metabolic demand, and further increase plasma ATP when superimposed with mild-intensity exercise. In young healthy adults, we measured forearm blood flow (FBF) (Doppler ultrasound) and plasma [ATP](v) (luciferin-luciferase assay), then calculated forearm ATP effluent (FBF×[ATP](v)) during rhythmic forearm compressions (RFC) via a blood pressure cuff at three graded pressures (50, 100, and 200 mmHg; Protocol 1; n = 10) and during RFC at 100 mmHg, 5% maximal voluntary contraction rhythmic handgrip exercise (RHG), and combined RFC + RHG (Protocol 2; n = 10). [ATP](v) increased from rest with each cuff pressure (range 144-161 vs. 64 ± 13 nmol/l), and ATP effluent was graded with pressure. In Protocol 2, [ATP](v) increased in each condition compared with rest (RFC: 123 ± 33; RHG: 51 ± 9; RFC + RHG: 96 ± 23 vs. Mean Rest: 42 ± 4 nmol/l; P < 0.05), and ATP effluent was greatest with RFC + RHG (RFC: 5.3 ± 1.4; RHG: 5.3 ± 1.1; RFC + RHG: 11.6 ± 2.7 vs. Mean Rest: 1.2 ± 0.1 nmol/min; P < 0.05). We conclude that the mechanical effects of muscle contraction can 1) independently elevate intravascular ATP draining quiescent skeletal muscle without changes in local metabolism and 2) further augment intravascular ATP during mild exercise associated with increases in metabolism and local deoxygenation; therefore, it is likely one stimulus for increasing intravascular ATP during exercise in humans. PMID:23429876

Crecelius, Anne R; Kirby, Brett S; Richards, Jennifer C; Dinenno, Frank A

2013-02-21

363

Apyrase Functions in Plant Phosphate Nutrition and Mobilizes Phosphate from Extracellular ATP  

Microsoft Academic Search

ATP, which is present in the extracellular matrix of multicellular organisms and in the extracellular fluid of unicellular organisms, has been shown to function as a signaling molecule in animals. The concentration of extracellular ATP (xATP) is known to be function- ally modulated in part by ectoapyrases, membrane-associated pro- teins that cleave the g- and b-phosphates on xATP. We present

Collin Thomas; Yu Sun; Katie Naus; Alan Lloyd; Stanley Roux

1999-01-01

364

Copper-dependent trafficking of Wilson disease mutant ATP7B proteins  

Microsoft Academic Search

We have previously developed a functional assay in yeast for the copper transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant ATP7B proteins revealed that several were able to completely, or nearly completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was disrupted, indicating that these ATP7B proteins retained copper transport activity. We analyzed the

John R. Forbes; Diane W. Cox

2000-01-01

365

The ydaO motif is an ATP-sensing riboswitch in Bacillus subtilis.  

PubMed

We report what is to our knowledge the first natural RNA that regulates gene expression in response to intracellular ATP. Using a biochemical screen, we found that several putative riboswitches bind ATP in vitro. The ydaO motif specifically bound ATP and regulated expression of endogenous and reporter genes in response to ATP concentrations in Bacillus subtilis. This discovery demonstrates a role for RNAs in regulating gene expression in response to energy balance in bacteria. PMID:23086297

Watson, Peter Y; Fedor, Martha J

2012-10-21

366

Lung epithelial cells release ATP during ozone exposure: signaling for cell survival.  

PubMed

The common air pollutant ozone causes acute toxicity to human airways. In primary and transformed epithelial cells from all levels of human or rat airways, ozone levels relevant to air pollution (50-200 ppb) increased extracellular [ATP] within 7-30 min. A human bronchial epithelial cell line (16HBE14o(-)) that forms electrically resistant polarized monolayers had up to 10-fold greater apical than basolateral surface extracellular [ATP] within 7 min of ozone exposure. Increased extracellular [ATP] appeared due to ATP secretion or release because (1) inhibition of ectonucleotidase (cell surface enzyme(s) which degrade ATP) by ozone did not occur until >120 min of ozone exposure and (2) brefeldin A, a secretory inhibitor, eliminated elevation of extracellular [ATP] without affecting intracellular ATP. Extracellular ATP protected against ozone toxicity in a P2Y receptor-dependent manner as (1) removal of ATP and adenosine by apyrase and adenosine deaminase, respectively, potentiated ozone toxicity, (2) extracellular supplementation with ATP, a poorly hydrolyzable ATP analog ATPgammaS, or UTP inhibited apoptotic and necrotic ozone-mediated cell death, and (3) ATP-mediated protection was eliminated by P2 and P2Y receptor inhibitors suramin and Cibacron blue (reactive blue 2), respectively. The decline in glucose uptake caused by prolonged ozone exposure was prevented by supplemental extracellular ATP, an effect blocked by suramin. Further, Akt and ERK phosphorylation resulted from exposure to supplemental extracellular ATP. Thus, extracellularly released ATP signals to prevent ozone-induced death and supplementation with ATP or its analogs can augment protection, at least in part via Akt and /or ERK signaling pathways and their metabolic effects. PMID:15964513

Ahmad, Shama; Ahmad, Aftab; McConville, Glen; Schneider, Barbara K; Allen, Corrie B; Manzer, Rizwan; Mason, Robert J; White, Carl W

2005-03-28

367

Dynamic modeling for shear stress induced ATP release from vascular endothelial cells  

Microsoft Academic Search

A dynamic model is proposed for shear stress induced adenosine triphosphate (ATP) release from endothelial cells (ECs). The\\u000a dynamic behavior of the ATP\\/ADP concentration at the endothelial surface by viscous shear flow is investigated through simulation\\u000a studies based on the dynamic ATP release model. The numerical results demonstrate that the ATP\\/ADP concentration against time\\u000a at endothelium-fluid interface predicted by the

Kai Rong Qin; Cheng Xiang; Zhe Xu; Ling Ling Cao; Shuzhi Sam Ge; Zong Lai Jiang

2008-01-01

368

The chloroplast genes encoding subunits of the H+ATP synthase  

Microsoft Academic Search

Three CF1 and three CF0 subunits of the chloroplast H+-ATP synthase are encoded on the chloroplast genome. The chloroplast atp genes are organized as two operons in plants but not in the green alga, Chlamydomonas reinhardtii. The atpBE or ß operon shows a relatively simple organisation and transcription pattern, while the atpIHFA or a operon is transcribed into a large

Graham S. Hudson; John G. Mason

1988-01-01

369

ATP Requirements and Small Interfering RNA Structure in the RNA Interference Pathway  

Microsoft Academic Search

We examined the role of ATP in the RNA interference (RNAi) pathway. Our data reveal two ATP-dependent steps and suggest that the RNAi reaction comprises at least four sequential steps: ATP-dependent processing of double-stranded RNA into small interfering RNAs (siRNAs), incorporation of siRNAs into an inactive ?360 kDa protein\\/RNA complex, ATP-dependent unwinding of the siRNA duplex to generate an active

Antti Nykänen; Benjamin Haley; Phillip D. Zamore

2001-01-01

370

Escrt-III  

Microsoft Academic Search

The sorting of transmembrane proteins (e.g., cell surface receptors) into the multivesicular body (MVB) pathway to the lysosomal\\/vacuolar lumen requires the function of the ESCRT protein complexes. The soluble coiled-coil-containing proteins Vps2, Vps20, Vps24, and Snf7 are recruited from the cytoplasm to endosomal membranes where they oligomerize into a protein complex, ESCRT-III. ESCRT-III contains two functionally distinct subcomplexes. The Vps20-Snf7

Markus Babst; David J. Katzmann; Eden J. Estepa-Sabal; Timo Meerloo; Scott D. Emr

2002-01-01

371

Definition and Quantitation in Ecology  

Microsoft Academic Search

AUSTIN1, in commenting on my communication2, has provided an example of the problems which arise in justifying a non-quantitative approach to a subject such as ecology. Austin attaches significance to an imprecision of definition in my examination of the relationships among functional properties of Californian grasslands, and concludes ``more adequate definitions are necessary before McNaughton's suggestions ... can profitably be

S. J. McNaughton

1968-01-01

372

Secretion of adenylate kinase 1 is required for extracellular ATP synthesis in C2C12 myotubes  

Microsoft Academic Search

Extracellular ATP (exATP) has been known to be a crit- ical ligand regulating skeletal muscle differentiation and contractibility. ExATP synthesis was greatly in- creased with the high level of adenylate kinase 1 (AK1) and ATP synthase ? during C2C12 myogenesis. The exATP synthesis was abolished by the knock-down of AK1 but not by that of ATP synthase ? in C2C12

Hyo-Jung Choo; Bong-Woo Kim; Oh-Bong Kwon; Chang Seok Lee; Jong-Soon Choi; Young-Gyu Ko

2008-01-01

373

Roles of AtpI and two YidC-type proteins from alkaliphilic Bacillus pseudofirmus OF4 in ATP synthase assembly and nonfermentative growth.  

PubMed

AtpI, a membrane protein encoded by many bacterial atp operons, is reported to be necessary for c-ring oligomer formation during assembly of some ATP synthase complexes. We investigated chaperone functions of AtpI and compared them to those of AtpZ, a protein encoded by a gene upstream of atpI that has a role in magnesium acquisition at near-neutral pH, and of SpoIIIJ and YqjG, two YidC/OxaI/Alb3 family proteins, in alkaliphilic Bacillus pseudofirmus OF4. A strain with a chromosomal deletion of atpI grew nonfermentatively, and its purified ATP synthase had a c-ring of normal size, indicating that AtpI is not absolutely required for ATP synthase function. However, deletion of atpI, but not atpZ, led to reduced stability of the ATP synthase rotor, reduced membrane association of the F(1) domain, reduced ATPase activity, and modestly reduced nonfermentative growth on malate at both pH 7.5 and 10.5. Both spoIIIJ and yqjG, but not atpI or atpZ, complemented a YidC-depleted Escherichia coli strain. Consistent with such overlapping functions, single deletions of spoIIIJ or yqjG in the alkaliphile did not affect membrane ATP synthase levels or activities, but functional specialization was indicated by YqjG and SpoIIIJ showing respectively greater roles in malate growth at pH 7.5 and 10.5. Expression of yqjG was elevated at pH 7.5 relative to that at pH 10.5 and in ?spoIIIJ strains, but it was lower than constitutive spoIIIJ expression. Deletion of atpZ caused the largest increase among the mutants in magnesium concentrations needed for pH 7.5 growth. The basis for this phenotype is not yet resolved. PMID:23123906

Liu, Jun; Hicks, David B; Krulwich, Terry A

2012-11-02

374

Roles of AtpI and Two YidC-Type Proteins from Alkaliphilic Bacillus pseudofirmus OF4 in ATP Synthase Assembly and Nonfermentative Growth  

PubMed Central

AtpI, a membrane protein encoded by many bacterial atp operons, is reported to be necessary for c-ring oligomer formation during assembly of some ATP synthase complexes. We investigated chaperone functions of AtpI and compared them to those of AtpZ, a protein encoded by a gene upstream of atpI that has a role in magnesium acquisition at near-neutral pH, and of SpoIIIJ and YqjG, two YidC/OxaI/Alb3 family proteins, in alkaliphilic Bacillus pseudofirmus OF4. A strain with a chromosomal deletion of atpI grew nonfermentatively, and its purified ATP synthase had a c-ring of normal size, indicating that AtpI is not absolutely required for ATP synthase function. However, deletion of atpI, but not atpZ, led to reduced stability of the ATP synthase rotor, reduced membrane association of the F1 domain, reduced ATPase activity, and modestly reduced nonfermentative growth on malate at both pH 7.5 and 10.5. Both spoIIIJ and yqjG, but not atpI or atpZ, complemented a YidC-depleted Escherichia coli strain. Consistent with such overlapping functions, single deletions of spoIIIJ or yqjG in the alkaliphile did not affect membrane ATP synthase levels or activities, but functional specialization was indicated by YqjG and SpoIIIJ showing respectively greater roles in malate growth at pH 7.5 and 10.5. Expression of yqjG was elevated at pH 7.5 relative to that at pH 10.5 and in ?spoIIIJ strains, but it was lower than constitutive spoIIIJ expression. Deletion of atpZ caused the largest increase among the mutants in magnesium concentrations needed for pH 7.5 growth. The basis for this phenotype is not yet resolved.

Liu, Jun; Hicks, David B.

2013-01-01

375

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis  

PubMed Central

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

376

POAM III Validation Summary  

NASA Astrophysics Data System (ADS)

The Polar Ozone and Aerosol Measurement (POAM) III instrument has been making solar occultation measurements at polar latitudes in both hemispheres since April 1998. To date this data set comprises more than 32,000 high-resolution (1 km) vertical profiles of O3, NO2 and H2O density, as well as aerosol extinction from 350 to 1018 nm. In this paper we summarize the status of the POAM III validation analysis for all retrieved species. Using spatially and temporally coincident measurements, the POAM III retrievals are compared with data from other satellites (HALOE, SAGE II, SAGE III), as well as both in-situ and remote sensing aircraft- and balloon-based instruments, including a large sampling of high-latitude ozonesondes. These measurements have been obtained both in routine operation, and as part of special campaigns (e.g., SOLVE I and II). The comparisons provide a statistical estimate of the POAM III retrieval accuracy and precision. Results of this validation analysis are compared for consistency with estimated retrieval errors obtained from a formal error analysis. POAM III data are of high quality and are publicly available for scientific investigations and for validation of new and soon-to-be-launched satellite instruments.

Lumpe, J. D.; Randall, C. E.; Bevilacqua, R. M.; Hoppel, K. W.; Nedoluha, G. E.; Prados, A. I.

2003-12-01

377

The Definition of El Niño.  

NASA Astrophysics Data System (ADS)

A review is given of the meaning of the term El Niño and how it has changed in time, so there is no universal single definition. This needs to be recognized for scientific uses, and precision can only be achieved if the particular definition is identified in each use to reduce the possibility of misunderstanding. For quantitative purposes, possible definitions are explored that match the El Niños identified historically after 1950, and it is suggested that an El Niño can be said to occur if 5-month running means of sea surface temperature (SST) anomalies in the Niño 3.4 region (5°N-5°S, 120°-170°W) exceed 0.4°C for 6 months or more. With this definition, El Niños occur 31% of the time and La Niñas (with an equivalent definition) occur 23% of the time. The histogram of Niño 3.4 SST anomalies reveals a bimodal character. An advantage of such a definition is that it allows the beginning, end, duration, and magnitude of each event to be quantified. Most El Niños begin in the northern spring or perhaps summer and peak from November to January in sea surface temperatures.

Trenberth, Kevin E.

1997-12-01

378

Peroxisomal ATP Import Is Essential for Seedling Development in Arabidopsis thaliana  

Microsoft Academic Search

Several recent proteomic studies of plant peroxisomes indicate that the peroxisomal matrix harbors multiple ATP- dependent enzymes and chaperones. However, it is unknown whether plant peroxisomes are able to produce ATP by substrate-level phosphorylation or whether external ATP fuels the energy-dependent reactions within peroxisomes. The existence of transport proteins that supply plant peroxisomes with energy for fatty acid oxidation and

Nicole Linka; Frederica L. Theodoulou; Richard P. Haslam; Marc Linka; Jonathan A. Napier; H. Ekkehard Neuhaus; A. P. M. Weber

2008-01-01

379

Evidence for Myocardial ATP Compartmentation from NMR Inversion Transfer Analysis of Creatine Kinase Fluxes  

Microsoft Academic Search

The interpretation of creatine kinase (CK) flux measured by 31P NMR magnetization transfer in vivo is complex because of the presence of competing reactions, metabolite compartmentation, and CK isozyme localization. In the isovolumic perfused rat heart, we considered the influence of both ATP compartmentation and ATP-Pi exchange on the forward (Ff: PCr ? ATP) and reverse (Fr) CK fluxes derived

F. Joubert; B. Gillet; J. L. Mazet; P. Mateo; J.-C. Beloeil; J. A. Hoerter

2000-01-01

380

A rapid method for determining ATP by the firefly luciferin-luciferase system  

Microsoft Academic Search

Zusammenfassung Eine schnelle Methode zur Bestimmung von ATP in picogramm-Mengen wird beschrieben. Die Grundlage für die Methode ist eine Reaktion zwischen ATP und einem Inkubationsansatz, der Luciferin, Mg2+ und partiell gereinigte Luciferase enthält, und ist zur Bestimmung von ATP in biologischem Material von unterschiedlicher Beschaffenheit (Bakterien, Pflanzen-und Tiergewebe) geeignet.

H. A. Neufeld; R. D. Towner; Judith Pace

1975-01-01

381

Modeling of basolateral ATP release induced by hypotonic treatment in A6 cells  

Microsoft Academic Search

ATP is released from the basolateral membrane of A6 epithelia in response to hypotonic treatment. This study addresses the problem of ATP diffusion through the permeable supports used to culture the cells. A theoretical analysis of a recently introduced experimental protocol is presented and a model of ATP diffusion through the compartments of the measuring system is proposed. The model

Mihaela Gheorghiu; Willy Van Driessche

2004-01-01

382

Ultrastructural alterations during ATP-induced secretion of lysosomal enzymes from rabbit polymorphonuclear leukocytes  

Microsoft Academic Search

Rabbit neutrophils incubated in low-ionic-strength media were stimulated by ATP to secrete lysosomal enzymes. This was greatly enhanced in the presence of cytochalasin B. ATP in these circumstances induced the cell to form large cytoplasmic extensions that were largely devoid of granules. In the presence of both ATP and cytochalasin B, however, the projections contained granules in close proximity to

P. M. Henson; J. E. Henson; E. L. Becker

1975-01-01

383

Defective ATP-dependent mucin secretion by cystic fibrosis pancreatic epithelial cells  

Microsoft Academic Search

The response of confluent monolayers of normal and cystic fibrosis (CF) pancreatic epithelial cells to stimulation by extracellular ATP and ATP analogues was investigated in terms of mucin secretion. Mucin secretion was measured as release of M1 antigens by a direct sandwich enzyme immunoassay. Extracellular ATP provoked rapid (?15 min) and strong mucin secretion (+480 ± 35%) by the normal

C. Montserrat; M. Merten; C. Figarella

1996-01-01

384

ATP and adenosine stimulate phosphatidylcholine secretion in type II pneumocytes by different mechanisms  

Microsoft Academic Search

ATP and adenosine (A) stimulate phosphatidylcholine (PC) secretion in type II cells. ATP stimulates approx. 5-fold while A stimulates only 2-fold. There is evidence that the effect of A is mediated by the Aâ subtype of the P⁠receptor and involves an increase in intracellular cAMP. The aim of this study was to determine if ATP and A stimulate PC

S. A. Rooney; A. M. Gilfillan

1987-01-01

385

Released ATP Is an Extracellular Cytotoxic Mediator in Salivary Histatin 5Induced Killing of Candida albicans  

Microsoft Academic Search

Salivary histatins (Hsts) are antifungal peptides with promise as therapeutic agents against candidiasis. Hst 5 kills the fungal pathogen Candida albicans via a mechanism that involves release of cellular ATP in the absence of cytolysis. Here we demonstrate that released ATP has a further role in Hst 5 killing. Incubation of the cells with ATP analogues induced cell death, and

SVETLANA E. KOSHLUKOVA; MARCELO W. B. ARAUJO; DIDI BAEV; MIRA EDGERTON

2000-01-01

386

Isolation and Identification of ATP-Secreting Bacteria from Mice and Humans?  

PubMed Central

In a recent report, ATP, which was possibly secreted by some intestinal bacteria, was shown to cause colitis in mice via Th17 cell differentiation. However, the ATP-secreting bacteria have not been isolated and identified. In the present study, we report that Enterococcus gallinarum, which is a vancomycin-resistant Gram-positive coccus isolated from mice and humans, secretes ATP.

Iwase, Tadayuki; Shinji, Hitomi; Tajima, Akiko; Sato, Fumiya; Tamura, Taku; Iwamoto, Takeo; Yoneda, Minoru; Mizunoe, Yoshimitsu

2010-01-01

387

Nerve Growth Factor and ATP Excite Different Neck Muscle Nociceptors in Anaesthetized Mice  

Microsoft Academic Search

Neck muscle nociception probably plays a major role in the pathophysiology of tension-type headache. Recent studies have demonstrated sustained facilitation of brainstem nociception due to noxious neck muscle input evoked by nerve growth factor (NGF) or ?,?-methylene ATP (ATP) in mice. Hypothesized different afferent pathways in NGF and ATP models were addressed by local application of tetrodotoxin (TTX) in neck

J Ellrich; A Makowska

2007-01-01

388

The effect of ATP analogs on posthydrolytic and force development steps in skinned skeletal muscle fibers.  

PubMed Central

ATP, 2-deoxy ATP (dATP), CTP, and UTP support isometric force and unloaded shortening velocity (Vu) to various extents (Regnier et al., Biophys. J. 74:3044-3058). Vu correlated with the rate of cross-bridge dissociation after the power stroke and the steady-state hydrolysis rate in solution, whereas force was modulated by NTP binding and cleavage. Here we studied the influence of posthydrolytic cross-bridge steps on force and fiber shortening by measuring isometric force and stiffness, the rate of tension decline (kPi) after Pi photogeneration from caged Pi, and the rate of tension redevelopment (ktr) after a sudden release and restretch of fibers. The slope of the force versus [Pi] relationship was the same for ATP, dATP, and CTP, but for UTP it was threefold less. ktr and kPi increased with increasing [Pi] with a similar slope for ATP, dATP, and CTP, but had an increasing magnitude of the relationship ATP < dATP < CTP. UTP reduced ktr but increased kPi. The results suggest that the rate constant for the force-generating isomerization increases with the order ATP < dATP < CTP < UTP. Simulations using a six-state model suggest that increasing the force-generating rate accounts for the faster kPi in dATP, CTP, and UTP. In contrast, ktr appears to be strongly affected by the rates of NTP binding and cleavage and the rate of the force-generating isomerization.

Regnier, M; Homsher, E

1998-01-01

389

Conserved properties of hydrogenosomal and mitochondrial ADP\\/ATP carriers: a common origin for both organelles  

Microsoft Academic Search

Mitochondria are one of the hallmarks of eukaryotic cells, exporting ATP in exchange for cytosolic ADP using ADP\\/ATP carriers (AAC) located in the inner mitochondrial membrane. In contrast, several evolutionarily important anaerobic eukaryotes lack mitochondria but contain hydrogenosomes, peculiar organelles of controversial ancestry that also supply ATP but, like some fermentative bacteria, make molecular hydrogen in the process. We have

Mark van der Giezen; Dirk Jan Slotboom; David S. Horner; Patricia L. Dyal; Marilyn Harding; Gang-Ping Xue; T. Martin Embley; Edmund R. S. Kunji

2002-01-01

390

7 CFR 3300.88 - Fees for U.S. ATP certificates.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300...EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION...Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for...

2013-01-01

391

Customer Satisfaction Findings from the Advanced Technology Program's Survey of ATP Applicants 2002.  

National Technical Information Service (NTIS)

During the first part of 2004, the Advanced Technology Program (ATP) and Westat, a survey research firm under contract to ATP, conducted a survey of all applicants to the 2002 ATP competition. Seventeen of the survey questions addressed issues of customer...

A. Wang J. Kerwin S. Campbell

2005-01-01

392

76 FR 13069 - Airworthiness Directives; BAE Systems (Operations) Limited Model ATP Airplanes; BAE Systems...  

Federal Register 2010, 2011, 2012, 2013

...BAE Systems (Operations) Limited Model ATP Airplanes; BAE Systems (Operations) Limited...The MCAI states: Early in the life of the ATP (circa 1989), a report was received that...contact. BAE Systems responded by issuing SB ATP- 27-11, describing a one-time...

2011-03-10

393

7 CFR 3300.88 - Fees for U.S. ATP certificates.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300...EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION...Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for...

2010-01-01

394

7 CFR 3300.88 - Fees for U.S. ATP certificates.  

Code of Federal Regulations, 2010 CFR

...2009-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300...EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION...Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for...

2009-01-01

395

Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+  

PubMed Central

The identity and forms of activating ligands for ion channels are fundamental to their physiological roles in rapid electrical signaling. P2X receptor channels are ATP-activated cation channels that serve important roles in sensory signaling and inflammation, yet the active forms of the nucleotide are unknown. In physiological solutions, ATP is ionized and primarily found in complex with Mg2+. Here we investigated the active forms of ATP and found that the action of MgATP2? and ATP4? differs between subtypes of P2X receptors. The slowly desensitizing P2X2 receptor can be activated by free ATP, but MgATP2? promotes opening with very low efficacy. In contrast, both free ATP and MgATP2? robustly open the rapidly desensitizing P2X3 subtype. A further distinction between these two subtypes is the ability of Mg2+ to regulate P2X3 through a distinct allosteric mechanism. Importantly, heteromeric P2X2/3 channels present in sensory neurons exhibit a hybrid phenotype, characterized by robust activation by MgATP2? and weak regulation by Mg2+. These results reveal the existence of two classes of homomeric P2X receptors with differential sensitivity to MgATP2? and regulation by Mg2+, and demonstrate that both restraining mechanisms can be disengaged in heteromeric channels to form fast and sensitive ATP signaling pathways in sensory neurons.

Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.

2013-01-01

396

Genetic Variation in ATP5O Is Associated with Skeletal Muscle ATP50 mRNA Expression and Glucose Uptake in Young Twins  

Microsoft Academic Search

Background: Impaired oxidative capacity of skeletal muscle mitochondria contribute to insulin resistance and type 2 diabetes (T2D). Furthermore, mRNA expression of genes involved in oxidative phosphorylation, including ATP5O, is reduced in skeletal muscle from T2D patients. Our aims were to investigate mechanisms regulating ATP5O expression in skeletal muscle and association with glucose metabolism, and the relationship between ATP5O single nucleotide

Tina Rönn; Pernille Poulsen; Tiinamaija Tuomi; Bo Isomaa; Leif Groop; Allan Vaag; Charlotte Ling

2009-01-01

397

LATE RECTAL SEQUELAE FOLLOWING DEFINITIVE RADIATION THERAPY FOR CARCINOMA OF THE UTERINE CERVIX: A DOSIMETRIC ANALYSIS  

Microsoft Academic Search

Purpose: This study attempted to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients treated with radiation therapy (RT) for cervical carcinoma. Methods and Materials: A total of 183 patients with cervical carcinoma (67 Stage I, 93 Stage II, and 23 Stage III) treated with definitive RT with a minimum of 2 years follow-up

JOHN C. ROESKE; ARNO J. MUNDT; HOWARD HALPERN; PATRICK SWEENEY; HAROLD SUTTON; CLAIRE POWERS; JACOB ROTMENSCH; STEVE WAGGONER; RALPH R. WEICHSELBAUM

398

Evidence for sustained ATP release from liver cells that is not mediated by vesicular exocytosis.  

PubMed

Extracellular ATP regulates many important cellular functions in the liver by stimulating purinergic receptors. Recent studies have shown that rapid exocytosis of ATP-enriched vesicles contributes to ATP release from liver cells. However, this rapid ATP release is transient, and ceases in ~30 s after the exposure to hypotonic solution. The purpose of these studies was to assess the role of vesicular exocytosis in sustained ATP release. An exposure to hypotonic solution evoked sustained ATP release that persisted for more than 15 min after the exposure. Using FM1-43 (N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide) fluorescence to measure exocytosis, we found that hypotonic solution stimulated a transient increase in FM1-43 fluorescence that lasted ~2 min. Notably, the rate of FM1-43 fluorescence and the magnitude of ATP release were not correlated, indicating that vesicular exocytosis may not mediate sustained ATP release from liver cells. Interestingly, mefloquine potently inhibited sustained ATP release, but did not inhibit an increase in FM1-43 fluorescence evoked by hypotonic solution. Consistent with these findings, when exocytosis of ATP-enriched vesicles was specifically stimulated by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), mefloquine failed to inhibit ATP release evoked by NPPB. Thus, mefloquine can pharmacologically dissociate sustained ATP release and vesicular exocytosis. These results suggest that a distinct mefloquine-sensitive membrane ATP transport may contribute to sustained ATP release from liver cells. This novel mechanism of membrane ATP transport may play an important role in the regulation of purinergic signaling in liver cells. PMID:21630025

Dolovcak, Svjetlana; Waldrop, Shar L; Xiao, Feng; Kilic, Gordan

2011-06-01

399

TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F F{sub 1}-ATP synthase and ubiquinone  

SciTech Connect

Mitochondria generate ATP and participate in signal transduction and cellular pathology and/or cell death. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) decreases hepatic ATP levels and generates mitochondrial oxidative DNA damage, which is exacerbated by increasing mitochondrial glutathione redox state and by inner membrane hyperpolarization. This study identifies mitochondrial targets of TCDD that initiate and sustain reactive oxygen production and decreased ATP levels. One week after treating mice with TCDD, liver ubiquinone (Q) levels were significantly decreased, while rates of succinoxidase and Q-cytochrome c oxidoreductase activities were increased. However, the expected increase in Q reduction state following TCDD treatment did not occur; instead, Q was more oxidized. These results could be explained by an ATP synthase defect, a premise supported by the unusual finding that TCDD lowers ATP/O ratios without concomitant changes in respiratory control ratios. Such results suggest either a futile cycle in ATP synthesis, or hydrolysis of newly synthesized ATP prior to release. The TCDD-mediated decrease in Q, concomitant with an increase in respiration, increases complex 3 redox cycling. This acts in concert with glutathione to increase membrane potential and reactive oxygen production. The proposed defect in ATP synthase explains both the greater respiratory rates and the lower tissue ATP levels.

Shertzer, Howard G. [Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056 Cincinnati, OH 45267-0056 (United States)]. E-mail: shertzhg@ucmail.uc.edu; Genter, Mary Beth [Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056 Cincinnati, OH 45267-0056 (United States); Shen, Dongxiao [Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056 Cincinnati, OH 45267-0056 (United States); Nebert, Daniel W. [Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056 Cincinnati, OH 45267-0056 (United States); Chen, Ying [Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056 Cincinnati, OH 45267-0056 (United States); Dalton, Timothy P. [Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056 Cincinnati, OH 45267-0056 (United States)

2006-12-15

400

The coupling ion in the methanoarchaeal ATP synthases: H(+) vs. Na(+) in the A(1)A(o) ATP synthase from the archaeon Methanosarcina mazei Gö1.  

PubMed

To establish a system to analyze ATP synthesis by the archaeal A(1)A(o) ATP synthase and to address the nature of the coupling ion, the operon encoding the A(1)A(o) ATP synthase from the mesophile Methanosarcina mazei Gö1 was cloned in an expression vector and it was expressed in the F(1)F(o) ATP synthase-negative mutant Escherichia coli DK8. Western blot analyses revealed that each of the subunits was produced, and the subunits assembled to a functional, membrane-embedded ATP synthase/ATPase. ATP hydrolysis was inhibited by dicyclohexylcarbodiimide but also by tributyltin, which turned out to be the most efficient inhibitor of the A(o) domain of A(1)A(o) ATP synthase known to date. ATP hydrolysis was not dependent on the Na(+) concentration of the medium, and inhibition of the enzyme by dicyclohexylcarbodiimide could not be relieved by Na(+). The enzyme present in the cytoplasmic membrane of E. coli catalyzed ATP synthesis driven by an artificial DeltapH but not by DeltapNa or DeltamuNa(+). PMID:17986085

Pisa, Kim Y; Weidner, Claudia; Maischak, Heiko; Kavermann, Holger; Müller, Volker

2007-12-01

401

Calcium induced ATP synthesis: Isotope effect, magnetic parameters and mechanism  

NASA Astrophysics Data System (ADS)

ATP synthesis by creatine kinase with calcium ions is accompanied by 43Ca/ 40Ca isotope effect: the enzyme with 43Ca 2+ was found to be 2.0 ± 0.3 times more active than enzymes, in which Ca 2+ ions have nonmagnetic nuclei 40Ca. The effect demonstrates that primary reaction in ATP synthesis is electron transfer between reaction partners, ?a( HO)n2+ ( n ? 3) and Ca 2+(ADP) 3-. It generates ion-radical pair, in which spin conversion results in the isotope effect. Magnetic parameters (g-factors and HFC constants a( 43Ca) and a( 31P)) confirm that namely terminal oxygen atom of the ADP ligand in the complex Ca 2+(ADP) 3- donates electron to the Ca( HO)n2+ ion.

Buchachenko, A. L.; Kuznetsov, D. A.; Breslavskaya, N. N.; Shchegoleva, L. N.; Arkhangelsky, S. E.

2011-03-01

402

Bioluminescence microscopy: application to ATP measurements in single living cells  

NASA Astrophysics Data System (ADS)

Bioluminescence microscopy can be used to measure intracellular cofactors and ionic concentrations (Ca2+, K+, ATP, NADH), as an alternative to micro- spectrophotometry and micro-fluorimetry, due to the development of sensitive detectors (cooled photomultipliers tubes and CCD). The main limitation comes from the very small and brief intensity of the emitted light. Our instrumentation based on an inverted microscope, equipped with high aperture immersion lenses is presented. Light intensity measurements are carried out through a photomultiplier sorted for low dark current and cooled at -5 degree(s)C to reduce thermal noise. Our first aim is to quantify ATP on single living cells using the firefly luciferin-luciferase couple. Experimental and kinetic aspects are presented to emphasize the potentialities of the technique.

Brau, Frederic; Helle, Pierre; Bernengo, Jean C.

1997-12-01

403

Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels.  

PubMed

Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%-2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death. PMID:23498975

Bartolome, Fernando; Wu, Hsiu-Chuan; Burchell, Victoria S; Preza, Elisavet; Wray, Selina; Mahoney, Colin J; Fox, Nick C; Calvo, Andrea; Canosa, Antonio; Moglia, Cristina; Mandrioli, Jessica; Chiò, Adriano; Orrell, Richard W; Houlden, Henry; Hardy, John; Abramov, Andrey Y; Plun-Favreau, Helene

2013-03-14

404

Biomimetic gel exhibiting self-beating motion in ATP solution.  

PubMed

Biomimetic material systems using stimuli-responsive polymers and gels have been widely studied for applications to artificial muscles, drug delivery systems, biosensors, etc. In almost all cases, however, the action is driven by on-off switching of external signals. In contrast, here we show a novel biomimetic gel to exhibit autonomous self-beating motion in ATP solution under constant condition, similar to heart muscle. An anionic polymer gel with phosphoric groups, in which creatine kinase was immobilized, was prepared. When the gel was immersed in the ATP solution, the enzymatic reaction occurs in the gel and the concentration of calcium ion changes periodically. Since the chelates between phosphoric groups and the divalent calcium ion, which acts a physical crosslinking point, are formed and dissociated periodically, the gel repeats swelling and deswelling autonomously. PMID:16283708

Yoshida, Ryo; Uesusuki, Yusuke

405

Students' interdisciplinary reasoning about "high-energy bonds" and ATP  

NASA Astrophysics Data System (ADS)

Students' sometimes contradictory ideas about ATP (adenosine triphosphate) and the nature of chemical bonds have been studied in the biology and chemistry education literatures, but these topics are rarely part of the introductory physics curriculum. We present qualitative data from an introductory physics course for undergraduate biology majors that seeks to build greater interdisciplinary coherence and therefore includes these topics. In these data, students grapple with the apparent contradiction between the energy released when the phosphate bond in ATP is broken and the idea that an energy input is required to break a bond. We see that students' perceptions of how each scientific discipline bounds the system of interest can influence how they justify their reasoning about a topic that crosses disciplines. This has consequences for a vision of interdisciplinary education that respects disciplinary perspectives while bringing them into interaction in ways that demonstrate consistency amongst the perspectives.

Dreyfus, Benjamin W.; Geller, Benjamin D.; Sawtelle, Vashti; Svoboda, Julia; Turpen, Chandra; Redish, Edward F.

2013-01-01

406

Diversity of Operation in ATP-dependent Chromatin Remodelers  

PubMed Central

Chromatin is actively restructured by a group of proteins that belong to the family of ATP-dependent DNA translocases. These chromatin remodelers can assemble, relocate or remove nucleosomes, the fundamental building blocks of chromatin. The family of ATP-dependent chromatin remodelers has many properties in common, but there are also important differences that may account for their varying roles in the cell. Some of the important characteristics of these complexes have begun to be revealed such as their interactions with chromatin and their mechanism of operation. The different domains of chromatin remodelers are discussed in terms of their targets and functional roles in mobilizing nucleosomes. The techniques that have driven these findings are discussed and how these have helped develop the current models for how nucleosomes are remodeled.

Hota, Swetansu K.; Bartholomew, Blaine

2011-01-01

407

Mossbauer spectra of trispyrrolidylcarbodithioates of Cr(III), Co(III), Ga(III), and In(III) doped with Fe(III). Evidence of cross relaxation between Fe(III)&sngbnd;Cr(III)  

Microsoft Academic Search

Mossabauer spectra have been measured at 298, 78, and 4.2°K on chromium (III), cobalt(III), gallium(III), and indium(III) trispyrrolidylcarbodithioates containing 1–35 at.% iron(III). At 4.2°K the usual six line pattern due to magnetic hyperfine splitting is observed for the iron(III) doped diamagnetic matrices. However, for the paramagnetic chromium (III) matrix, a five line spectrum is found at iron concentrations of 1–18

Stephen F. Krzeminski; Darel K. Straubt

1973-01-01

408

The ATPases of Propionigenium modestum and Bacillus alcalophilus. Strategies for ATP synthesis under low energy conditions.  

PubMed

In Propionigenium modestum, ATP synthesis is coupled via delta mu Na+ to the decarboxylation of (S)-methylmalonyl-CoA. The low energy yield of this reaction implies that approx. 4 decarboxylation cycles are necessary to synthesize 1 molecule of ATP. Theoretical considerations in accord with experimental results suggest ATP synthesis in P. modestum at delta mu Na+ = -110 mV. Other anaerobic bacteria synthesize ATP at a delta mu H+ of similar size and alkaliphilic bacteria at pH 10.3 have a delta mu H+ of only -103 mV. In these cases, the H+(Na+) to ATP stoichiometry must be at least 4. PMID:1385980

Dimroth, P

1992-07-17

409

Extracellular ATP4- promotes cation fluxes in the J774 mouse macrophage cell line  

SciTech Connect

Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine 5'-(beta, gamma-imido)triphosphate (AMP-PNP) and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma-S) also stimulated /sup 86/Rb+ efflux, albeit at higher concentrations than that required for ATP4-. Exposure of J774 cells to 10 mM ATP for 45 min caused death of 95% of cells. By this means we selected variant J774 cells that did not exhibit /sup 86/Rb+ efflux in the presence of extracellular ATP but retained ecto-ATPase activity. These results show that the ecto-ATPase of J774 cells does not mediate the effects of ATP on these cells; that ATP4- and not MgATP2- promotes /sup 86/Rb+ efflux from these cells; and that hydrolysis of ATP is not required to effect this change in membrane permeability. These findings suggest that J774 cells possess a plasma membrane receptor which binds ATP4-, AMP-PNP, and ATP-gamma-S, and that the ecto-ATPase limits the effects of ATP on these cells by hydrolyzing Mg-ATP2-.

Steinberg, T.H.; Silverstein, S.C.

1987-03-05

410

Order Promising Rolling Planning with ATP\\/CTP Reallocation Mechanism  

Microsoft Academic Search

Available-to-promise (ATP) exhibiting availability of manufacturing resources can be used to sup- port customer order promising. Recently, one advanced function called Capable-to-promise (CTP) is provided by several modern APS (advanced planning system) that checks available capacity for placing new production orders or increasing already scheduled production orders. At the customer enquiry stage while considering the order delivery date and quantity

Juin-Han Chen; James T. Lin; Yi-Sheng Wu

2008-01-01

411

Inhibition of Escherichia coli ATP synthase by amphibian antimicrobial peptides  

PubMed Central

Previously melittin, the ?-helical basic honey bee venom peptide, was shown to inhibit F1-ATPase by binding at the ?-subunit DELSEED motif of F1Fo ATP synthase. Herein, we present the inhibitory effects of the basic ?-helical amphibian antimicrobial peptides, ascaphin-8, aurein 2.2, aurein 2.3, carein 1.8, carein 1.9, citropin 1.1, dermaseptin, maculatin 1.1, maganin II, MRP, or XT-7, on purified F1 and membrane bound F1Fo E. coli ATP synthase. We found that the extent of inhibition by amphibian peptides is variable. Whereas MRP-amide inhibited ATPase essentially completely (~96% inhibition), carein 1.8 did not inhibit at all (0% inhibition). Inhibition by other peptides was partial with a range of ~13% to 70%. MRP-amide was also the most potent inhibitor on molar scale (IC50 ~3.25 µM). Presence of an amide group at the c-terminal of peptides was found to be critical in exerting potent inhibition of ATP synthase (~20–40% additional inhibition). Inhibition was fully reversible and found to be identical in both F1Fo membrane preparations as well as in isolated purified F1. Interestingly, growth of Escherichia coli was abrogated in the presence of ascaphin-8, aurein 2.2, aurein 2.3, citropin 1.1, dermaseptin, magainin II-amide, MRP, MRP-amide, melittin, or melittin-amide but was unaffected in the presence of carein 1.8, carein 1.9, maculatin 1.1, magainin II, or XT-7. Hence inhibition of F1-ATPase and E. coli cell growth by amphibian antimicrobial peptides suggests that their antimicrobial/anticancer properties are in part linked to their actions on ATP synthase.

Laughlin, Thomas F.; Ahmad, Zulfiqar

2010-01-01

412

Simulation of narrowband power line communication using ATP-EMTP  

Microsoft Academic Search

The simulation of narrowband power line communication is carried out by use of the J. Marti line model in the ATP-EMTP simulation program. The modal attenuation constants for three distribution line structures are obtained and frequency domain simulations on a ‘typical’ rural 11 kV network are carried out. It follows that the 11 kV network studied presents a channel to

Stephen Robson; Manu Haddad; Huw Griffiths

2009-01-01

413

Experimental non-ATP-competitive therapies for chronic myelogenous leukemia  

Microsoft Academic Search

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy driven by the BCR-ABL fusion tyrosine kinase. The central role played by BCR-ABL1 in the pathogenesis of CML facilitated the development of the tyrosine kinase inhibitor (TKI) imatinib mesylate, the first actual targeted therapy in cancer history. Imatinib competes with ATP at the active site of BCR-ABL1 kinase. Despite outstanding

A Quintás-Cardama

2008-01-01

414

ATP-binding cassette, subfamily G (ABCG family)  

Microsoft Academic Search

This review summarizes the characteristics of the ATP-binding cassette, subfamily G (ABCG family), which has five members:\\u000a ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. The members consist of a single ABC cassette in the amino terminal followed by six\\u000a putative transmembrane domains, and to become functionally active, they form homo- or obligate heterodimers. Except for ABCG2,\\u000a the members of the ABCG

Hiroyuki Kusuhara; Yuichi Sugiyama

2007-01-01

415

Association and Stoichiometry of K ATP Channel Subunits  

Microsoft Academic Search

ATP-sensitive potassium channels (KATP channels) are heteromultimers of sulfonylurea receptors (SUR) and inwardly rectifying potassium channel subunits (KIR6.x) with a (SUR–KIR6.x)4 stoichiometry. Association is specific for KIR6.x and affects receptor glycosylation and cophotolabeling of KIR6.x by 125I-azidoglibenclamide. Association produces digitonin stable complexes with an estimated mass of 950 kDa. These complexes can be purified by lectin chromatography or by using

John P. Clement IV; Kumud Kunjilwar; Gabriela Gonzalez; Mathias Schwanstecher; Uwe Panten; Lydia Aguilar-Bryan; Joseph Bryan

1997-01-01

416

ATP as a mediator of macula densa cell signalling.  

PubMed

Within each nephro-vascular unit, the tubule returns to the vicinity of its own glomerulus. At this site, there are specialised tubular cells, the macula densa cells, which sense changes in tubular fluid composition and transmit information to the glomerular arterioles resulting in alterations in glomerular filtration rate and blood flow. Work over the last few years has characterised the mechanisms that lead to the detection of changes in luminal sodium chloride and osmolality by the macula densa cells. These cells are true "sensor cells" since intracellular ion concentrations and membrane potential reflect the level of luminal sodium chloride concentration. An unresolved question has been the nature of the signalling molecule(s) released by the macula densa cells. Currently, there is evidence that macula densa cells produce nitric oxide via neuronal nitric oxide synthase (nNOS) and prostaglandin E(2) (PGE(2)) through cyclooxygenase 2 (COX 2)-microsomal prostaglandin E synthase (mPGES). However, both of these signalling molecules play a role in modulating or regulating the macula-tubuloglomerular feedback system. Direct macula densa signalling appears to involve the release of ATP across the basolateral membrane through a maxi-anion channel in response to an increase in luminal sodium chloride concentration. ATP that is released by macula densa cells may directly activate P2 receptors on adjacent mesangial cells and afferent arteriolar smooth muscle cells, or the ATP may be converted to adenosine. However, the critical step in signalling would appear to be the regulated release of ATP across the basolateral membrane of macula densa cells. PMID:19330465

Bell, P Darwin; Komlosi, Peter; Zhang, Zhi-Ren

2009-03-28

417

ATP-dependent proteases that also chaperone protein biogenesis  

Microsoft Academic Search

The ATP-dependent proteases Clp and FtsH from bacteria, as well as mitochondrial homologs of FtsH and Lon from yeast, may act as chaperones; they mediate not only proteolysis, but also the insertion of proteins into membranes and the disassembly or oligomerization of protein complexes. The coordination of such processes with selective proteolysis may function in the quality control of protein

Carolyn K. Suzuki; Martijn Rep; Jan Maarten van Dijl; Kitaru Suda; Leslie A. Grivell; Gottfried Schatz

1997-01-01

418

Electron transfer coupled with ATP hydrolysis in nitrogenase  

Microsoft Academic Search

Nitrogenase, which is not a membrane protein in vivo, performs energy coupling: the transfer of an electron coupled with ATP hydrolysis from one protein component of nitrogenase, Fe protein (Av2), to another its protein component, MoFe protein (Av1), to form the so-called “super-reduced state” of the active site responsible for the reduction of the substrates, FeMo cofactor (FeMoco) containing Fe,

L. A. Syrtsova; E. A. Timofeeva

2001-01-01

419

The distinctiveness of ATP:citrate lyase from Aspergillus nidulans  

Microsoft Academic Search

ATP:citrate lyase (ACL), an important enzyme in lipid synthesis, has been purified from Aspergillus nidulans to a specific activity of 19.6 ?mol min?1 mg?1, almost twice that of any other purified ACL and shown to be distinct from any previously purified ACL. The enzyme is a 371±31 kDa hexamer of 3?, 3? proteins, unlike the 4? tetramer found in rats

Ian P. Adams; Stephen Dack; F. Mark Dickinson; Colin Ratledge

2002-01-01

420

ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation  

Microsoft Academic Search

Histone acetylation in single-cell eukaryotes relies on acetyl coenzyme A (acetyl-CoA) synthetase enzymes that use acetate to produce acetyl-CoA. Metazoans, however, use glucose as their main carbon source and have exposure only to low concentrations of extracellular acetate. We have shown that histone acetylation in mammalian cells is dependent on adenosine triphosphate (ATP)-citrate lyase (ACL), the enzyme that converts glucose-derived

Kathryn E. Wellen; Georgia Hatzivassiliou; Uma M. Sachdeva; Thi V. Bui; Justin R. Cross; Craig B. Thompson

2009-01-01

421

Multiple chromatographic forms of ATP citrate lyase from rat liver.  

PubMed

ATP citrate lyase is shown to exist as multiple forms in extracts of rat liver. DEAE-Sephadex ion-exchange chromatography of liver supernatants reveals two peaks of activity. A minor, basic, component, comprising 14% of the recovered activity, is eluted without retention, whereas the major, acidic, form is eluted by a KCl gradient. Gel filtration of similar extracts shows the presence of a high-Mr form of ATP citrate lyase (Mr around 10(7) in addition to the tetrameric enzyme (Mr 4.1 X 10(5). This associated state, which represents 10% of the total activity, is unstable, breaking down to the tetramer, and appears to be disrupted by Mg2+. The basic form changes in the partially purified state to give the acidic form. Most of the high-Mr enzyme is acidic in nature. No evidence could be found for an association of the enzyme with mitochondrial or microsomal membranes. ATP citrate lyase from rat brain also shows two peaks of activity on DEAE-Sephadex ion-exchange chromatography, but the activity is distributed between the peaks in almost equal proportions. However, only the tetrameric enzyme was observed on gel filtration. PMID:6615476

Corrigan, A P; Rider, C C

1983-08-15

422

The Unbinding of ATP from F1-ATPase  

PubMed Central

Using molecular dynamics, we study the unbinding of ATP in F1-ATPase from its tight binding state to its weak binding state. The calculations are made feasible through use of interpolated atomic structures from Wang and Oster [Nature 1998, 396: 279–282]. These structures are applied to atoms distant from the catalytic site. The forces from these distant atoms gradually drive a large primary region through a series of sixteen equilibrated steps that trace the hinge bending conformational change in the ?-subunit that drives rotation of ?-subunit. As the rotation progresses, we find a sequential weakening and breaking of the hydrogen bonds between the ATP molecule and the ?- and ?-subunits of the ATPase. This finding agrees with the “binding-zipper” model [Oster and Wang, Biochim. Biophys. Acta 2000, 1458: 482–510.] In this model, the progressive formation of the hydrogen bonds is the energy source driving the rotation of the ?-shaft during hydrolysis. Conversely, the corresponding sequential breaking of these bonds is driven by rotation of the shaft during ATP synthesis. Our results for the energetics during rotation suggest that the nucleotide's coordination with Mg2+ during binding and release is necessary to account for the observed high efficiency of the motor.

Antes, Iris; Chandler, David; Wang, Hongyun; Oster, George

2003-01-01

423

Structure of the mitochondrial ATP synthase by electron cryomicroscopy  

PubMed Central

We have determined the structure of intact ATP synthase from bovine heart mitochondria by electron cryomicroscopy of single particles. Docking of an atomic model of the F1-c10 subcomplex into a major segment of the map has allowed the 32 ? resolution density to be interpreted as the F1-ATPase, a central and a peripheral stalk and an FO membrane region that is composed of two domains. One domain of FO corresponds to the ring of c-subunits, and the other probably contains the a-subunit, the transmembrane portion of the b-subunit and the remaining integral membrane proteins of FO. The peripheral stalk wraps around the molecule and connects the apex of F1 to the second domain of FO. The interaction of the peripheral stalk with F1-c10 implies that it binds to a non-catalytic ?–? interface in F1 and its inclination where it is not attached to F1 suggests that it has a flexible region that can serve as a stator during both ATP synthesis and ATP hydrolysis.

Rubinstein, John L.; Walker, John E.; Henderson, Richard

2003-01-01

424

Sulfide oxidation coupled to ATP synthesis in chicken liver mitochondria.  

PubMed

Chicken liver mitochondria consumed O2 at an accelerated rate when supplied with low concentrations of hydrogen sulfide. Maximum respiration occurred in 10 microM sulfide, and continued more slowly up to concentrations as high as 60 microM. Sulfide oxidation was coupled to adenosine triphosphate (ATP) synthesis, as shown by firefly luciferase luminescence and by measurement of the mitochondrial membrane electrochemical gradient. Synthesis of ATP required low, steady-state concentrations of sulfide (< 5 microM), which were maintained by use of a syringe pump. The ratio of consumed O2 to sulfide changed at low sulfide and O2 concentrations, indicating alternative metabolic reactions and products. In low concentrations of sulfide, presumably most similar to physiological, the O2/sulfide ratio was 0.75. This is the first report of sulfide oxidation linked to ATP synthesis in any organism not specifically adapted to a sulfide-rich environment. We suggest that this may be a widespread mitochondrial trait, and that it is consistent with the hypothesis that mitochondria originated from sulfide-oxidizing symbionts. PMID:11337256

Yong, R; Searcy, D G

2001-05-01

425

Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes  

PubMed Central

Viability of the tsetse fly-transmitted African trypanosome Trypanosoma brucei depends on maintenance and expression of its kinetoplast (kDNA), the mitochondrial genome of this parasite and a putative target for veterinary and human antitrypanosomatid drugs. However, the closely related animal pathogens T. evansi and T. equiperdum are transmitted independently of tsetse flies and survive without a functional kinetoplast for reasons that have remained unclear. Here, we provide definitive evidence that single amino acid changes in the nuclearly encoded F1FO–ATPase subunit ? can compensate for complete physical loss of kDNA in these parasites. Our results provide insight into the molecular mechanism of compensation for kDNA loss by showing FO-independent generation of the mitochondrial membrane potential with increased dependence on the ADP/ATP carrier. Our findings also suggest that, in the pathogenic bloodstream stage of T. brucei, the huge and energetically demanding apparatus required for kDNA maintenance and expression serves the production of a single F1FO–ATPase subunit. These results have important implications for drug discovery and our understanding of the evolution of these parasites.

Dean, Samuel; Gould, Matthew K.; Dewar, Caroline E.; Schnaufer, Achim C.

2013-01-01

426

Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes.  

PubMed

Viability of the tsetse fly-transmitted African trypanosome Trypanosoma brucei depends on maintenance and expression of its kinetoplast (kDNA), the mitochondrial genome of this parasite and a putative target for veterinary and human antitrypanosomatid drugs. However, the closely related animal pathogens T. evansi and T. equiperdum are transmitted independently of tsetse flies and survive without a functional kinetoplast for reasons that have remained unclear. Here, we provide definitive evidence that single amino acid changes in the nuclearly encoded F1FO-ATPase subunit ? can compensate for complete physical loss of kDNA in these parasites. Our results provide insight into the molecular mechanism of compensation for kDNA loss by showing FO-independent generation of the mitochondrial membrane potential with increased dependence on the ADP/ATP carrier. Our findings also suggest that, in the pathogenic bloodstream stage of T. brucei, the huge and energetically demanding apparatus required for kDNA maintenance and expression serves the production of a single F1FO-ATPase subunit. These results have important implications for drug discovery and our understanding of the evolution of these parasites. PMID:23959897

Dean, Samuel; Gould, Matthew K; Dewar, Caroline E; Schnaufer, Achim C

2013-08-19

427

Contesting Definitional Authority in the Collective  

ERIC Educational Resources Information Center

The field of rhetoric has generated studies of definitional disputes and of the relationship between definition and power. Informed by the idea of collective definition created over time, these studies raise an important theoretical-practical question about definition and contestation that may be approached through a concept of authority.…

Clarke, Lynn

2005-01-01

428

Developing a Standard Definition of Intermodal Transportation  

Microsoft Academic Search

Despite the growing emphasis being placed on intermodal transportation by government and industry, a consensus definition of intermodal transportation does not exist. The purpose of this paper is to propose a standard definition for intermodal transportation. Several definitions for intermodal transportation are presented, compared and critiqued. Themes common to this cross-section of definitions are combined with other potentially important concepts

W. Brad Jones; C. Richard Cassady; Royce O. Bowden

429

What is Cybersex? Heterosexual Students’ Definitions  

Microsoft Academic Search

This study examined university students’ definitions of cybersex. Participants (N = 292) provided a written definition of the term “cybersex” and completed background, cybersex, and online sexual activity measures. Qualitative analysis of the written definitions revealed eight content categories and two broad conceptualizations in the data. Cybersex was consistently defined as an interactive activity. However, definitions also reflected substantial individual

Krystelle Shaughnessy; Sandra Byers; Sara Jane Thornton

2011-01-01

430

Direct activation of cloned K(atp) channels by intracellular acidosis.  

PubMed

ATP-sensitive K(+) (K(ATP)) channels may be regulated by protons in addition to ATP, phospholipids, and other nucleotides. Such regulation allows a control of cellular excitability in conditions when pH is low but ATP concentration is normal. However, whether the K(ATP) changes its activity with pH alterations remains uncertain. In this study we showed that the reconstituted K(ATP) was strongly activated during hypercapnia and intracellular acidosis using whole-cell recordings. Further characterizations in excised patches indicated that channel activity increased with a moderate drop in intracellular pH and decreased with strong acidification. The channel activation was produced by a direct action of protons on the Kir6 subunit and relied on a histidine residue that is conserved in all K(ATP). The inhibition appeared to be a result of channel rundown and was not seen in whole-cell recordings. The biphasic response may explain the contradictory pH sensitivity observed in cell-endogenous K(ATP) in excised patches. Site-specific mutations of two residues showed that pH and ATP sensitivities were independent of each other. Thus, these results demonstrate that the proton is a potent activator of the K(ATP). The pH-dependent activation may enable the K(ATP) to control vascular tones, insulin secretion, and neuronal excitability in several pathophysiologic conditions. PMID:11278532

Xu, H; Cui, N; Yang, Z; Wu, J; Giwa, L R; Abdulkadir, L; Sharma, P; Jiang, C

2001-01-25

431

Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes.  

PubMed

A paradigm for control of insulin secretion is that glucose metabolism elevates cytoplasmic [ATP]/[ADP] in beta cells, closing K(ATP) channels and causing depolarization, Ca2+ entry, and insulin release. Decreased responsiveness of K(ATP) channels to elevated [ATP]/[ADP] should therefore lead to decreased insulin secretion and diabetes. To test this critical prediction, we generated transgenic mice expressing beta cell K(ATP) channels with reduced ATP sensitivity. Animals develop severe hyperglycemia, hypoinsulinemia, and ketoacidosis within 2 days and typically die within 5. Nevertheless, islet morphology, insulin localization, and alpha and beta cell distributions were normal (before day 3), pointing to reduced insulin secretion as causal. The data indicate that normal K(ATP) channel activity is critical for maintenance of euglycemia and that overactivity can cause diabetes by inhibiting insulin secretion. PMID:10761930

Koster, J C; Marshall, B A; Ensor, N; Corbett, J A; Nichols, C G

2000-03-17

432

P2X-purinoceptors in the heart: actions of ATP and UTP.  

PubMed

Positive inotropic effects of ATP and UTP (1 microM - 1mM) were studied in isolated rat and guinea pig cardiac tissues. The potency order obtained was ATP>UTP in both species, suggesting possible interaction with P2X-purinoceptors. Binding studies using [(3)H]alpha,beta-methylene ATP as marker of P2X-purinoceptors revealed two receptor sites: one high-, the other low-affinity, in atria and ventricles from rat and guinea pig. Both ATP and UTP were found to bind high-affinity sites of [(3)H]alpha,beta-methylene ATP. The effects of various calcium inhibitors such as nifedipine, dantrolene, ryanodine and TMB-8 on positive inotropic effects induced by ATP and UTP were also studied. The results suggest that ATP and UTP may increase inotropism by interaction with P2X-purinoceptors by means of a calcium-dependent mechanism. PMID:9126862

Froldi, G; Varani, K; Chinellato, A; Ragazzi, E; Caparrotta, L; Borea, P A

1997-01-01

433

Contributions of citrate in redox potential maintenance and ATP production: metabolic pathways and their regulation in Lactobacillus panis PM1.  

PubMed

Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli and can utilize various NADH-reoxidizing routes (e.g., citrate, glycerol, and oxygen) according to environmental conditions. In this study, we investigated the ability of L. panis PM1 to produce succinate, acetate, and lactate via citrate utilization. Possible pathways, as well as regulation, for citrate metabolism were examined on the basis of the genome sequence data and metabolic profiles of L. panis PM1. The presence of citrate led to the up-regulation, at the transcriptional level, of the genes encoding for citrate lyase, malate dehydrogenase, and malic enzyme of the citrate pathways by 10- to 120-fold. The transcriptional regulator of the dha operon coding for glycerol dehydratase of L. panis PM1 repressed the expression of the citrate lyase gene (10-fold). Metabolite analyses indicated that the transcriptional enhancement by citrate stimulated succinate yield. Citrate metabolism contributed to energy production by providing a major alternate pathway for NAD(+) regeneration and allowed acetyl phosphate to yield acetate/ATP instead of ethanol/NAD(+). Additionally, a branching pathway from oxaloacetate to pyruvate increased the pool of lactate, which was then used to produce ATP during stationary phase. However, the redirection of NADH-to-citrate utilization resulted in stress caused by end-products (i.e., succinate and acetate). This stress reduced succinate production by up to 50 % but did not cause significant changes at transcriptional level. Overall, citrate utilization was beneficial for the growth of L. panis PM1 by providing a NAD(+) regeneration route and producing extra ATP. PMID:23912115

Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2013-08-04

434

[Cloning and expression of atp6 and atp9 genes from ramie (Boehmeria nivea (L.) Gaud.) and their relationship with cytoplasmic male sterility].  

PubMed

The atp6 and apt9 gene fragments associated with cytoplasmic male sterility (CMS) were cloned from the mitochondrial DNA of a ramie (Boehmeria nivea (L.) Gaud.) cytoplasmic male sterile line and its maintainer and restorer lines using PCR and degenerated primer strategy. The primers were designed according to the reserved sequences in the encoding region of mitochondrial genes atp6 and atp9 of some dicotyledons from GenBank. These fragments did not have complete encoding region but showed the homology of 94% and 85% with atp6 and atp9 genes from the referred dicotyledons in GenBank. The complete atp6 and atp9 genes including the complete open reading frames were cloned by means of amplifying the 3' and 5'end unknown sequences of these gene fragments using DNA Walking method. The atp6 gene showed no difference among ramie male sterile line, maintainer and restorer lines at mtDNA sequence, transcription and translation control and protein level. However, compared to the maintainer and restorer lines, the atp9 gene of the male sterile line was different and deletion in several bases at the 3' end of the encoding region. An abnormally high expression of atp9 gene in the male sterile line at the budding stage and full-bloom stage was analyzed by RT-PCR analysis. These results indicated that the variation in DNA sequence and/or abnormality in expression of atp9 gene in the male sterile line maybe closely related to ramie CMS. PMID:19073559

Duan, Ji-Qiang; DU, Guang-Hui; Li, Jian-Yong; Liang, Xue-Ni; Liu, Fei-Hu

2008-11-01

435

Toward a Multiscale Description of Microvascular Flow Regulation: O2-Dependent Release of ATP from Human Erythrocytes and the Distribution of ATP in Capillary Networks  

PubMed Central

Integration of the numerous mechanisms that have been suggested to contribute to optimization of O2 supply to meet O2 need in skeletal muscle requires a systems biology approach which permits quantification of these physiological processes over a wide range of length scales. Here we describe two individual computational models based on in vivo and in vitro studies which, when incorporated into a single robust multiscale model, will provide information on the role of erythrocyte-released ATP in perfusion distribution in skeletal muscle under both physiological and pathophysiologi