AimTo investigate whether the downregulation of heat shock protein 90 (HSP90) was involved in cardiac cell injury induced by serum-glucose deprivation (SGD).MethodsH9c2 cardiomyocytes (H9c2 cells) were treated with SGD to establish an in vitro model of ischemic cardiac cell injury.H9c2 cells were pretreated with 17-AAG (a selective inhibitor of HSP90) for 60 min before exposure of cells to SGD.Cell viability was detected by CCK-8.The intracellular level of free calcium was measured by Fluo-3AM staining and photofluorography.The expressions of HSP90 and glucose-regulated protein 78 (GPR78) were tested by Western blot assay.ResultsTreatment of H9c2 cells with SGD for 24 h significantly induced downregulation of HSP90 expression, overload of intracellular calcium, and upregulation of GRP78 expression, which is a marker of endoplasmic reticulum stress.Pretreatment with 17-AAG, a selective HSP90 inhibitor, not only aggravated SGD-induced decrease in the viability of H9c2 cells, but also enhanced SGD-induced overload of intracellular calcium and upregulation of GRP78 expression in H9c2 cells.ConclusionInhibition of HSP90 may be one of the key mechanisms, by which H9c2 cells were damaged by SGD.