IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase
Zhang, Gai-Gai1; Cai, Huai-Qiu2; Li, Yan-Hui3; Sui, Yu-Bin2; Zhang, Jin-Sheng3; Chang, Jin-Rui3; Ning, Ming1; Wu, Yang1; Tang, Chao-Shu3; Qi, Yong-Fen3; Yin, Xin-Hua2
关键词Ghrelin Heart Endoplasmic Reticulum Stress Apoptosis Amp-activated Protein Kinase
刊名PEPTIDES
2013-10-01
DOI10.1016/j.peptides.2013.08.015
48页:156-165
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
研究领域[WOS]Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
关键词[WOS]ENDOPLASMIC-RETICULUM STRESS ; MYOCARDIAL ENERGY-METABOLISM ; ISCHEMIA/REPERFUSION INJURY ; TRANSGENIC MICE ; ISCHEMIC-HEART ; RAT-HEART ; ISOPROTERENOL ; CARDIOMYOCYTES ; FAILURE ; PEPTIDE
英文摘要

Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), is a cardioprotective peptide. In our previous work, we have revealed that ghrelin could protect heart against ischemia/reperfusion (I/R) injury by inhibiting endoplasmic reticulum stress (ERS), which contributes to many heart diseases. In current study, using both in vivo and in vitro models, we investigated how ghrelin inhibits myocardial ERS. In the in vivo rat heart injury model induced by isoproterenol (ISO), we found that exogenous ghrelin could alleviate heart dysfunction, reduce myocardial injury and apoptosis and inhibit the excessive myocardial ERS induced by ISO. More importantly, the activation of AMP-activated protein kinase (AMPK) was observed. To explore the role of AMPK activation in ERS inhibition by ghrelin, we set up two in vitro ERS models by exposing cultured rat cardiomyocytes to tunicamycin(Tm) or dithiothreitol (DTT). In both models, compared with Tm or DTT treatment alone, pre-incubation cardiomyocytes with ghrelin significantly activated AMPK, reversed the upregulation of the ERS markers, C/EBP-homologous protein (CHOP) and cleaved caspase-12, and reduced apoptosis of cardiomyocytes. Further, we found that the ERS inhibitory and anti-apoptotic actions induced by ghrelin were blocked by an AMPK inhibitor. To investigate how ghrelin activates AMPK, selective antagonist of GHS-R1a and inhibitor of Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK) were added, respectively, before ghrelin pre-incubation, and we found that AMPK activation was prevented and the ERS inhibitory and anti-apoptotic actions of ghrelin were blocked. In conclusion, ghrelin could protect heart against ERS-induced injury and apoptosis, at least partially through a GHS-R1a/CaMKK/AMPK pathway. (C) 2013 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000324998300020
项目编号81000046 ; 81170082
资助机构National Natural Science Foundation of China
引用统计
被引频次:25[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52048
专题北京大学基础医学院_心血管所
北京大学基础医学院
作者单位1.Tsinghua Univ, Affiliated Hosp 1, Beijing Huaxin Hosp, Dept Geriatr & Gerontol, Beijing 100016, Peoples R China
2.Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin 150086, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
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GB/T 7714
Zhang, Gai-Gai,Cai, Huai-Qiu,Li, Yan-Hui,et al. Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase[J]. PEPTIDES,2013,48:156-165.
APA Zhang, Gai-Gai.,Cai, Huai-Qiu.,Li, Yan-Hui.,Sui, Yu-Bin.,Zhang, Jin-Sheng.,...&Yin, Xin-Hua.(2013).Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase.PEPTIDES,48,156-165.
MLA Zhang, Gai-Gai,et al."Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase".PEPTIDES 48(2013):156-165.
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