Abstract
Signal mechanisms of regulatory volume increase (RVI) in HeLa cells and of RVI inhibition under apoptotic stimulationTakahashi, Nobuyuki; Subramanian, Muthangi; Okada, Yasunobu (Dept. Cell Physiol., Natl. Inst. Physiol. Sci., Okazaki, Japan)Most cells show cell volume recovery, called regulatory volume increase (RVI), after osmotic shrinkage. However, under apoptotic conditions, cell volume persistently decreases without exhibiting RVI. In human epithelial HeLa cells exposed to hypertonic solution, RVI was significantly inhibited by an Akt blocker. Moreover, exogenous expression of the dominant negative form of Akt inhibited RVI under hypertonic conditions. Akt was phosphorylated by hypertonicity, and this phosphorylation was inhibited by apoptotic stimulation by staurosporine, H2O2, or TNF-α. Either of these apoptotic stimuli suppressed RVI and then induced apoptotic cell death. Apoptosis signal-regulating kinase 1 (ASK1) was found to be activated by either apoptosis inducer. Overexpression of the kinase dead mutant of ASK1 restored both shrinkage-induced Akt phosphorylation and RVI under apoptotic conditions. Thus, it is concluded that Akt activation induced by hypertonicity is involved in the RVI mechanism in HeLa cells and that shrinkage-induced Akt activation is inhibited by ASK1 activated by various apoptotic stimuli thereby leading to persistent cell shrinkage in apoptotic cells. [J Physiol Sci. 2006;56 Suppl:S117]
