Institutional Repository of Peking University School of Basic Medical Sciences
|Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca2+ uptake via K-ATP channel and PI3K/Akt pathway|
|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|
|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|
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.
|项目编号||2012CB517806 ; 30890042 ; 81170235 ; 81070114 ; 81121061|
|资助机构||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|
|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
|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.|
|APA||Chen, Yu,Zhao, Jing,Du, Junbao,Xu, Guoheng,Tang, Chaoshu,&Geng, Bin.(2012).Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca2+ uptake via K-ATP channel and PI3K/Akt pathway.LIFE SCIENCES,91(7-8),271-278.|
|MLA||Chen, Yu,et al."Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca2+ uptake via K-ATP channel and PI3K/Akt pathway".LIFE SCIENCES 91.7-8(2012):271-278.|