Vasopressin-induced hypertrophy in H9c2 heart-derived myocytes
Vasopressin-induced hypertrophy in H9c2 heart-derived myocytes
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DOI：
10.1016/s1357-2725(00)00037-6
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发表时间：
2000-09-01
影响因子：
4
通讯作者：
Bostrom, CO
中科院分区：
文献类型：
--
作者：
Brostrom, MA;Reilly, BA;Bostrom, CO
H9c2心肌细胞的蛋白质合成对精氨酸加压素(1um)有双时相反应。最初50%的抑制可归因于肌浆/内质网的钙动员，随后是恢复，随后转化为1.5倍的刺激。这项研究是为了确定加压素是否使H9c2细胞肥大或增殖，以及编程是否需要早期的翻译抑制。翻译抑制仅在加压素浓度(>；1 nM)时观察到，导致广泛的(>；50%)钙储存耗竭，并在超生理细胞外钙浓度时减弱。相反，对蛋白质合成的刺激不受依赖于基因转录的细胞外钙离子变化的影响，被蛋白激酶C假底物序列(肽19-27)抑制，并在ph1加压素浓度下观察到。MAP激酶、肌醇磷脂3-激酶、钙调神经磷酸酶、S6激酶、olelF4不参与刺激，持续24 h。细胞蛋白积累发生在PM激素浓度下，被19-27肽阻断，观察到无论维甲酸预防肌源性转分化，都可以观察到细胞蛋白积累，并在完全补充钙库之前观察到。H9c2细胞具有V1受体信号的所有基本特征，为研究血管加压素诱导的心肌细胞肥大提供了一个方便的模型。血管加压素诱导的H9c2心肌细胞肥大不需要早期的翻译抑制，而蛋白激酶C的激活似乎是必不可少的。(C)2000爱思唯尔科学有限公司。保留所有权利。
Protein synthesis in H9c2 heart-derived myocytes responds biphasically to arginine vasopressin (1 muM). An initial 50% inhibition attributable to Ca2+ mobilization from the sarcoplasmic/endoplasmic reticulum is followed by a recovery that subsequently converts to a 1.5-fold stimulation. This study was undertaken to ascertain whether vasopressin programs H9c2 cells to undergo hypertrophy or to proliferate and whether early translational inhibition is required for programming. Translational suppression was observed only at vasopressin concentrations (>1 nM) causing extensive (> 50%) depletion of Ca2+ stores and was diminished at supraphysiologic extracellular Ca2+ concentrations. Stimulation of protein synthesis, by contrast, was unaffected by changes in extracellular Ca2+ depended on gene transcription, was suppressed by a protein kinase C pseudosubstrate sequence (peptide 19-27), and was observed at phl vasopressin concentrations. Activation of MAP kinases, phosphoinositide 3-kinase, calcineurin, S6 kinase, ol elF4 could not be implicated in the stimulation, which persisted for 24 h. Vasopressin-treated H9c2 cells underwent hypertrophy by standard criteria. Cellular protein accumulation occurred at pM hormone concentrations, was blocked by peptide 19-27, was observed regardless of retinoic acid pretreatment to prevent myogenic transdifferentiation, and preceded full repletion of Ca2+ stores. It is proposed that H9c2 cells, which possess all basic features of V1-vasoplessin receptor signaling, provide a convenient model for investigating vasopressin-induced myocyte hypertrophy. Early translational suppression is not needed for vasopressin-induced H9c2 myocyte hypertrophy whereas activation of protein kinase C appears essential. (C) 2000 Elsevier Science Ltd. All rights reserved.