北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 心血管所  > 期刊论文
学科主题: 基础医学
题名:
Exendin-4 alleviates angiotensin II-induced senescence in vascular smooth muscle cells by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway
作者: Zhao, Liang1,2; Li, Ai Q.1,2; Zhou, Teng F.1,2; Zhang, Meng Q.1,2; Qin, Xiao M.1,2
关键词: Exendin-4 ; angiotensin II ; senescence ; NAD(P)H oxidase
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
发表日期: 2014-12-15
DOI: 10.1152/ajpcell.00151.2014
卷: 307, 期:12, 页:C1130-C1141
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Physiology
研究领域[WOS]: Cell Biology ; Physiology
关键词[WOS]: GLUCAGON-LIKE PEPTIDE-1 ; ELEVATION MYOCARDIAL-INFARCTION ; GLP-1 RECEPTOR AGONISTS ; ENDOTHELIAL-CELLS ; PREMATURE SENESCENCE ; CELLULAR SENESCENCE ; NADPH OXIDASES ; HUMAN ATHEROSCLEROSIS ; INDEPENDENT PATHWAYS ; MOLECULAR-MECHANISMS
英文摘要:

Vascular aging has been implicated in the progression of diabetes and age-related cardiovascular disorders. Glucagon-like peptide-1 (GLP-1) is an incretin hormone capable of cytoprotective actions in addition to its glucose-lowering effect. The present study was undertaken to examine whether Exendin-4, a specific ligand for the GLP-1 receptor, could prevent angiotensin (ANG) II-induced premature senescence in vascular smooth muscle cells (VSMCs) and to determine the underlying mechanism involved. Senescence-associated beta-galactosidase (SA beta-gal) assay showed that ANG II induced premature senescence of VSMCs. Pretreatment with Exendin-4 significantly attenuated ANG II-induced generation of H2O2 and the subsequent VSMC senescence. These effects were, however, reversed in the presence of exendin fragment 9-39, a GLP-1 receptor antagonist, or PKI14-22. Moreover, a marked increase in the levels of p53 and p21 induced by ANG II was blunted by the treatment with Exendin-4. Nevertheless, Exendin-4 failed to decrease ANG II-induced expression of NAD(P)H oxidase 1 (Nox1), NAD(P)H oxidase 4 (Nox4), p22(phox), or p47(phox) in VSMCs. Mechanistically, Exendin-4 blocked ANG II-induced Rac1 activation through the cAMP/PKA signaling cascade. Specifically, NSC23766, a Rac1 inhibitor, abrogated the suppressive effects of Exendin-4 on ANG II-induced premature senescence and H2O2 generation, respectively. Thus Exendin-4 confers resistance to ANG II-induced superoxide anion generation from NAD(P)H oxidase and the resultant VSMC senescence by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway. These findings demonstrate that GLP-1 as well as its analogs (GLP-1-related reagents) may hold therapeutic potential in the treatment of diabetes with cardiovascular disease.

语种: 英语
所属项目编号: 30700292 ; 30971160 ; 31271493
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000346473400008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53768
Appears in Collections:基础医学院_心血管所_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
C1130.full.pdf(537KB)期刊论文作者接受稿限制开放 联系获取全文

作者单位: 1.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China

Recommended Citation:
Zhao, Liang,Li, Ai Q.,Zhou, Teng F.,et al. Exendin-4 alleviates angiotensin II-induced senescence in vascular smooth muscle cells by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2014,307(12):C1130-C1141.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Zhao, Liang]'s Articles
[Li, Ai Q.]'s Articles
[Zhou, Teng F.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Zhao, Liang]‘s Articles
[Li, Ai Q.]‘s Articles
[Zhou, Teng F.]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace