| High-affinity Na(+)-dependent dicarboxylate cotransporter promotes cellular senescence by inhibiting SIRT1. | |
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MedLine Citation:
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PMID: 20813124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High-affinity Na(+)-dependent dicarboxylate cotransporter (NaDC3) can transport Krebs cycle intermediates into cells. Our previous study has shown that NaDC3 promotes cellular senescence, but its mechanism is not clear. It is known that when the concentration of intermediates in Krebs cycle is increased, NAD(+)/NADH ratio will be decreased. NAD(+)-dependent histone deacetylase sirtuin1 (SIRT1) prolongs mammalian cellular lifespan. Therefore, we propose that NaDC3 accelerates cellular aging by inhibiting SIRT1. After NaDC3 was overexpressed in two human embryo lung fibroblastic cell lines, WI38 and MRC-5, we found that the cells displayed aging-related phenotypes in advance. Meanwhile, the level of SIRT1 activity was down-regulated. In WI38/hNaDC3 cells treated with the activators of SIRT1, aging-related phenotypes induced by NaDC3 were obviously improved. The NAD(+)/NADH ratio in WI38/hNaDC3 cells was also decreased. Further study found that enhanced intracellular NAD(+) level could attenuate the aging phenotypes induced by NaDC3. Thus, NaDC3 promotes cellular senescence probably by inhibiting NAD(+)-dependent SIRT1. |
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Authors:
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Weiping Liu; Quan Hong; Xue-Yuan Bai; Bo Fu; Yuansheng Xie; Xueguang Zhang; Jianjun Li; Suozhu Shi; Yang Lv; Xuefeng Sun; Xiangmei Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-09 |
Journal Detail:
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Title: Mechanisms of ageing and development Volume: 131 ISSN: 1872-6216 ISO Abbreviation: Mech. Ageing Dev. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2011-01-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0347227 Medline TA: Mech Ageing Dev Country: Ireland |
Other Details:
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Languages: eng Pagination: 601-13 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Nephrology, Chinese PLA Institute of Nephrology & Key Lab, Chinese PLA General Hospital, Beijing, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Aging / physiology* Cell Line Citric Acid Cycle / physiology Humans Male NAD / genetics, metabolism Organic Anion Transporters, Sodium-Dependent / genetics, metabolism* Rats Rats, Wistar Sirtuin 1 / antagonists & inhibitors, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Organic Anion Transporters, Sodium-Dependent; 53-84-9/NAD; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirt1 protein, rat; EC 3.5.1.-/Sirtuin 1 |
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