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学科主题: 基础医学
题名:
Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca2+ uptake via K-ATP channel and PI3K/Akt pathway
作者: Chen, Yu1,2; Zhao, Jing1; Du, Junbao3; Xu, Guoheng1; Tang, Chaoshu1,2; Geng, Bin1,2
关键词: Hydrogen sulfide ; Ca2+ uptake ; Sarcoplamic reticulum Ca2+-ATPase ; Phospholamban
刊名: LIFE SCIENCES
发表日期: 2012-09-17
DOI: 10.1016/j.lfs.2012.07.026
卷: 91, 期:7-8, 页:271-278
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: NITRIC-OXIDE SYNTHASE ; RAT CARDIOMYOCYTES ; REPERFUSION INJURY ; CALCIUM-TRANSPORT ; HYPERTENSIVE-RATS ; CARDIOPROTECTION ; AKT ; ACTIVATION ; MYOCYTES ; H2S
英文摘要:

Aims: To investigate the effects of hydrogen sulfide (H2S) on calcium uptake activity of the rat cardiac sarcoplasmic reticulum (SR) and possible signaling.

Main methods: Crude SR was isolated after treatment with H2S, then SR Ca2+ uptake and SR Ca2+-ATPase (SERCA) activity was measured by the isotopic tracer method. The possible roles of the K-ATP channel and PI3K/Akt and SR-membrane protein phospholamban (PLB) pathway were analyzed by specific blockers, and target protein activation was assayed by measuring protein phosphorylation.

Key findings: Exogenous H2S lowered Ca2+ uptake into the SR time or concentration dependently, which was associated with decreased SERCA activity. Inhibiting endogenous H2S production by DL-propargylglycine increased SR Ca2+ uptake and SERCA activity. H2S inhibition of PLB phosphorylation was through SERCA activity and was reversed by two PI3K inhibitors, wortmannin and LY294002. Glibenclamide (a K-ATP, channel blocker) blocked the inhibitory effects of H2S on PLB and Akt phosphorylation. Pinacidil (a K-ATP channel opener) reduced the phosphorylation of PLB and reversed the effects of DL-propargylglycine. H2S preconditioning increased PLB phosphorylation but did not affect SERCA activity.

Significance: Endogenous H2S transiently and reversibly inhibits SR Ca2+ uptake in rat heart SR because of downregulated SERCA activity associated with PLB phosphorylation by the PI3K/Akt or K-ATP channel. The transient negative regulation of SR Ca2+ uptake and the L-type Ca2+ channel contributes to Ca2+ cycle homeostasis, which might be an important molecular mechanism in ischemic diseases. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 2012CB517806 ; 30890042 ; 81170235 ; 81070114 ; 81121061
项目资助者: Major State Basic Research Development Program of the People&prime ; s Republic of China ; National Natural Science Foundation of People&prime ; s Republic of China
WOS记录号: WOS:000308681300008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54217
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 1, Inst Cardiovasc Res, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 1, Dept Pediat, Beijing 100191, Peoples R China

Recommended Citation:
Chen, Yu,Zhao, Jing,Du, Junbao,et al. Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca2+ uptake via K-ATP channel and PI3K/Akt pathway[J]. LIFE SCIENCES,2012,91(7-8):271-278.
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