Vasopressin-induced hypertrophy in H9c2 heart-derived myocytes

Protein synthesis in H9c2 heart-derived myocytes responds biphasically to a rginine 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 w as undertaken to ascertain whether vasopressin programs H9c2 cells to under go hypertrophy or to proliferate and whether early translational inhibition is required for programming. Translational suppression was observed only a t vasopressin concentrations (>1 nM) causing extensive (> 50%) depletion of Ca2+ stores and was diminished at supraphysiologic extracellular Ca2+ conc entrations. Stimulation of protein synthesis, by contrast, was unaffected b y changes in extracellular Ca2+ depended on gene transcription, was suppres sed by a protein kinase C pseudosubstrate sequence (peptide 19-27), and was observed at phl vasopressin concentrations. Activation of MAP kinases, pho sphoinositide 3-kinase, calcineurin, S6 kinase, ol elF4 could not be implic ated in the stimulation, which persisted for 24 h. Vasopressin-treated H9c2 cells underwent hypertrophy by standard criteria. Cellular protein accumul ation occurred at pM hormone concentrations, was blocked by peptide 19-27, was observed regardless of retinoic acid pretreatment to prevent myogenic t ransdifferentiation, and preceded full repletion of Ca2+ stores. It is prop osed that H9c2 cells, which possess all basic features of V1-vasoplessin re ceptor 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 prot ein kinase C appears essential. (C) 2000 Elsevier Science Ltd. All rights r eserved.