Ghrelin inhibits apoptosis signal-regulating kinase 1 activity via upregulating heat-shock protein 70
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- 作者：Min Yang ; Shengdi Hu ; Bin Wu ; Yanying Miao ; Hui Pan ; Shigong Zhu
- 关键词：Ghrelin ; Apoptosis ; ASK1 ; HSP70
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 出版时间：27 July 2007
- 年：2007
- 卷：359
- 期：2
- 页码：373-378
- 全文大小：204 K
文摘
Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which has been originally isolated from rat stomach. It has been reported that ghrelin inhibited apoptosis in several cells, such as cardiomyocytes, endothelial cells, adipocyte, adrenal zona glomerulosa cells, pancreatic β-cells, osteoblastic MC3T3-E1 cells, intestinal epithelial cells and hypothalamic neurons. However, it is unknown whether heat-shock protein 70 (HSP70) or apoptosis signal-regulating kinase 1 (ASK1) is the important target molecule which mediates the anti-apoptotic effects of ghrelin. We show that ghrelin inhibited ASK1 activity induced by sodium nitroprusside (SNP), inhibited ASK1-mediated caspase 3 activation and apoptosis in PC12 cells. Ghrelin promoted expression of HSP70. Quercetin, an inhibitor of HSP70, blocked the effects of ghrelin on ASK1 activity. Thus, ghrelin inhibits ASK1-mediated apoptosis and ASK1 activation by a mechanism involving induction of HSP70 expression. The results of the present study suggest the therapeutic potential of ghrelin for some pathological processes or disorders.