Ghrelin inhibits apoptosis induced by high glucose and sodium palmitate in adult rat cardiomyocytes through the PI3K-Akt signaling pathway

被引：85

作者：

Liu Kui ^{[1
]}

Zhang Weiwei ^{[1
]}

Liu ling ^{[2
]}

He Daikun ^{[1
]}

Zhou Guoming ^{[3
]}

Zhou Linuo ^{[1
]}

Hu Renming ^{[1
]}

机构：

[1] Fudan Univ, Huashan Hosp, Dept Endocrinol & Metab, Shanghai 200040, Peoples R China

[2] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200040, Peoples R China

[3] Fudan Univ, Shanghai Med Coll, Dept Histol & Embryol, Shanghai 200040, Peoples R China

来源：

REGULATORY PEPTIDES | 2009年 / 155卷 / 1-3期

关键词：

Cardiomyocytes; Ghrelin; Oxidative stress; Apoptosis; PI3K; MITOCHONDRIAL PERMEABILITY TRANSITION; CHRONIC HEART-FAILURE; GROWTH-FACTOR-I; NF-KAPPA-B; OXIDATIVE STRESS; CELL-DEATH; PHOSPHOINOSITIDE; 3-KINASE; DIABETIC CARDIOMYOPATHY; MESSENGER-RNA; ACTIVATION;

D O I：

10.1016/j.regpep.2009.03.003

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective: Ghrelin is a gastric acyl-peptide that has been identified as an endogenous ligand for the growth hormone secretagogue receptor. It has been reported to have cardioprotective activities independent of growth hormone release. We investigated the effect of ghrelin on apoptosis induced by high glucose and sodium palmitate and the mechanisms underlying the cardioprotective activities of ghrelin. Research design and methods: Cardiomyocytes were isolated from hearts of adult rats and cultured in serum-free MEM. High glucose (30 mM) or sodium palmitate (0.5 mM) were used to induce apoptosis. Apoptosis was detected using an annexin V-FITC/PI binding assay and a caspase 3 activity assay. Reactive oxygen species were detected using a DCFH-DA fluorescent probe. Phospho-Akt, phospho-ERK, and NF kappa B levels were determined using ELISA. The transcription of genes was analyzed using real-time PCR. Results: Ghrelin can inhibit apoptosis induced by oxidative stress in cardiomyocytes from adult rats through the activation of the PI3K-Akt signaling pathway. In addition, ghrelin does not decrease intracellular oxidative stress. Activation of the MEK-ERK1/2 signaling pathway has no influence on the inhibition of apoptosis. Finally, ghrelin activates NF kappa B and subsequently increases the transcription of survival genes such as Bcl-2, Bcl-xL, c-iap, and c-fos. Conclusion: Our research provides evidence that ghrelin may act as a survival factor under oxidative stress in cardiomyocytes. This may provide a clue for therapy for myocardial disease in diabetes mellitus. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：62 / 69

页数：8

共 57 条

[1]

Ghrelin and growth hormone secretagogue receptor are expressed in the rat adrenal cortex: evidence that ghrelin stimulates the growth, but not the secretory activity of adrenal cells [J].