Vasopressin-induced hypertrophy in H9c2 heart-derived myocytes

Abstract

Protein synthesis in H9c2 heart-derived myocytes responds biphasically to arginine vasopressin (1 μM). An initial 50% inhibition attributable to Ca 2+ 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 Ca 2+ stores and was diminished at supraphysiologic extracellular Ca 2+ concentrations. Stimulation of protein synthesis, by contrast, was unaffected by changes in extracellular Ca 2+, depended on gene transcription, was suppressed by a protein kinase C pseudosubstrate sequence (peptide 19–27), and was observed at pM vasopressin concentrations. Activation of MAP kinases, phosphoinositide 3-kinase, calcineurin, S6 kinase, or eIF4 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 Ca 2+ stores. It is proposed that H9c2 cells, which possess all basic features of V1-vasopressin 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.