Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes
Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes
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DOI：
10.1016/j.cardiores.2004.01.024
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发表时间：
2004-06-01
影响因子：
10.8
通讯作者：
Lago, F
中科院分区：
文献类型：
--
作者：
Iglesias, MJ;Piñeiro, R;Lago, F
目的：Ghrelin。生长激素促分泌素受体（GHS-R）的内源性配体，作用于垂体和下丘脑以刺激生长激素（GH）的释放并促进食欲和肥胖。据报道，它还可以增加心肌收缩力，诱导血管舒张。并防止心肌梗塞引起的心力衰竭。虽然主要来源于胃，但它也由其他组织产生。这项工作研究了心肌细胞是否合成和分泌ghrelin，以及它在这些细胞中的产生如何响应压力和外源性凋亡剂。研究方法：采用RT-PCR、免疫组织化学和竞争结合法研究了Ghrelin及其受体在小鼠心肌细胞系HL-1和原代培养的人心肌细胞中的表达。用放射免疫法测定心肌细胞培养液中Ghrelin的含量。MTT法和Hoechst染色法检测细胞活力和凋亡。结果如下：RT-PCR显示HL-1细胞产生ghrelin和GHS-R的mRNA，并且GHS-R1 a在人心肌细胞中表达;使用I-125标记的ghrelin的竞争性结合研究显示GHS-R在HL-1细胞表面的有效组成型表达。免疫组织化学证实了生长素释放肽的存在下，HL-1细胞和分离的人心肌细胞的原代培养的细胞质中。放射免疫分析显示，HL-1细胞和人心肌细胞均可分泌Ghrelin进入培养液。Ghrelin对HL-1细胞饥饿12小时后的存活率无明显影响，但对阿糖胞苷（AraC）具有保护作用。最后，HL-1心肌细胞生长素释放肽mRNA的产生减少阿糖胞苷，但增加，如果暴露于阿糖胞苷之前，生长激素治疗。结论：Ghrelin由分离的鼠和人心肌细胞合成和分泌，可能具有旁分泌/自分泌效应，并且可能参与保护这些细胞免于凋亡。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Ghrelin. the endogenous ligand of growth hormone secretaogue receptor(GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation. and protect against myocardial-infarction-induced heart failure. Though principally gastric in origin, it is also produced by other tissues. This work investigated whether cardiomyocytes synthesize and secrete ghrelin, and how its production in these cells responds to stress and exogenous apoptotic agents. Methods: Ghrelin and its receptor expression was studied by RT-PCR, immunohistochemistry, and competitive binding studies in mouse adult cardiomyocyte cell line HL-1, and primary Cultured human cardiomyocytes. Ghrelin accumulation in cardiomyocyte Culture medium was measured by radio immunoassay. Viability and apoptosis assays were carried on by MTT and Hoechst dye vital staining, respectively. Results: RT-PCR showed that HL-1 cells produce mRNAs for both ghrelin and GHS-R, and that GHS-R1a is expressed in human cardiomyocytes; and competitive binding studies using I-125-labelled ghrelin showed efficient constitutive expression of GHS-R at the Surface of HL-1 cells. Immunohistochemistry confirmed the presence of ghrelin in the cytoplasm of HL-1 cells and of isolated human cardiomyocytes in primary culture. Radioimmunoassay showed that ghrelin was secreted by HL-1 cells and human cardiomyocytes into the culture medium. Ghrelin did not modify the viability of HL-1 Cells subjected to 12-h starvation, but did protect against the apoptosis inducer cytosine arabinoside (AraC). Finally, production of ghrelin mRNA in HL-1 cardiomyocytes was reduced by AraC but increased if exposure to AraC was preceded by GH treatment. Conclusions: Ghrelin is synthesized and secreted by isolated murine and human cardiomyocytes, probably with paractine/autocrine effects, and may be involved in protecting these cells from apoptosis. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.