科学研究中文献、数据、信息、知识、情报的综合利用
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科学杂志 Science. 2010 Mar 5;327(5970):1223-8.
论文题目 estrin as a feedback inhibitor of TOR that prevents age-related pathologies.
论文作者:Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, Ocorr K, Ellisman MH, Bodmer R, Bier E, Karin M.
作者机构:Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093-0723, USA.
Comment in: 对本文的评论
Abstract 摘要
Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO). Loss of dSesn resulted in age-associated pathologies including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction, which were prevented by pharmacological activation of AMPK or inhibition of TOR. Hence, dSesn appears to be a negative feedback regulator of TOR that integrates metabolic and stress inputs and prevents pathologies caused by chronic TOR activation that may result from diminished autophagic clearance of damaged mitochondria, protein aggregates, or lipids.
PMID: 20203043 [PubMed - indexed for MEDLINE]PMCID: PMC2866632 [Available on 2011/3/5]
Publication Types, MeSH Terms, Substances, Grant Support
Publication Types: 文献类型
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
MeSH Terms: 医学主题词
- AMP-Activated Protein Kinases/metabolism
- Aging*
- Amino Acid Sequence
- Animals
- Autophagy
- Cell Size
- Drosophila Proteins/antagonists & inhibitors
- Drosophila Proteins/chemistry
- Drosophila Proteins/genetics
- Drosophila Proteins/metabolism
- Drosophila Proteins/physiology*
- Drosophila melanogaster/cytology
- Drosophila melanogaster/growth & development
- Drosophila melanogaster/metabolism
- Drosophila melanogaster/physiology*
- Fat Body/metabolism
- Feedback, Physiological
- Forkhead Transcription Factors/metabolism
- Gene Expression Regulation
- Heart/physiology
- Heat-Shock Proteins/chemistry
- Heat-Shock Proteins/genetics
- Heat-Shock Proteins/physiology*
- JNK Mitogen-Activated Protein Kinases/metabolism
- Mitochondria, Muscle/physiology
- Mitochondria, Muscle/ultrastructure
- Models, Animal
- Molecular Sequence Data
- Muscles/physiology
- Oxidative Stress
- Protein Kinases/metabolism*
- Reactive Oxygen Species/metabolism
- Signal Transduction
- Transcription, Genetic
- Triglycerides/metabolism
- Wing/cytology
- Wing/growth & development
- Wing/metabolism
Substances: 物质名称
- Drosophila Proteins
- FOXO protein, Drosophila
- Forkhead Transcription Factors
- Heat-Shock Proteins
- Reactive Oxygen Species
- Triglycerides
- Protein Kinases
- target of rapamycin protein, Drosophila
- AMP-Activated Protein Kinases
- JNK Mitogen-Activated Protein Kinases
Grant Support: 基金资助信息
- AI070654/AI/NIAID NIH HHS/United States
- CA118165/CA/NCI NIH HHS/United States
- DK082080/DK/NIDDK NIH HHS/United States
- ES006376/ES/NIEHS NIH HHS/United States
- NS29870/NS/NINDS NIH HHS/United States
- P30-CA23100/CA/NCI NIH HHS/United States
- P41-RR004050/RR/NCRR NIH HHS/United States
- P42-ES010337/ES/NIEHS NIH HHS/United States
LinkOut - more resources 全球信息资源链接
Full Text Sources: 全文提供机构(出版商)
Other Literature Sources: 本研究论文同时在以下几个网站上
- Evaluations and comments from leading biologists - Faculty of 1000 Biology
- Evaluations and comments from leading researchers and clinicians - Faculty of 1000 Medicine
Medical: 医学知识平台
Libraries: 图书馆
- LinkOut Holdings 信息资源馆藏机构
原始文献期刊网站
- Cell biology. Burn out
or fade away? [Science. 2010]
Cell biology. Burn out or fade away?Topisirovic I, Sonenberg N. Science. 2010 Mar 5; 327(5970):1210-1.
- JNK/FOXO-mediated
neuronal expression of fly homologue of peroxiredoxin II reduces
oxidative stress and extends life span. [J Biol
Chem. 2009]
JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span.Lee KS, Iijima-Ando K, Iijima K, Lee WJ, Lee JH, Yu K, Lee DS. J Biol Chem. 2009 Oct 23; 284(43):29454-61. Epub 2009 Aug 31.
- Increased Rheb-TOR
signaling enhances sensitivity of the whole organism to oxidative
stress. [J Cell Sci. 2006]
Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress.Patel PH, Tamanoi F. J Cell Sci. 2006 Oct 15; 119(Pt 20):4285-92.
- Expression of Drosophila
FOXO regulates growth and can phenocopy starvation. [BMC Dev Biol. 2003]
Expression of Drosophila FOXO regulates growth and can phenocopy starvation.Kramer JM, Davidge JT, Lockyer JM, Staveley BE. BMC Dev Biol. 2003 Jul 5; 3:5. Epub 2003 Jul 5.
- Review
Drosophila aging 2005/06. [Exp Gerontol. 2006]
Review Drosophila aging 2005/06.Lim HY, Bodmer R, Perrin L. Exp Gerontol. 2006 Dec; 41(12):1213-6. Epub 2006 Nov 28.
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