Activation of stress response by ionomycin in rat hepatoma cells

All living systems respond to a variety of stress conditions by inducing the synthesis of stress or heat shock proteins (HSPs), which transiently protect cells. HSP synthesis was preceded by an increase in intracellular free calcium concentration [(Ca2+)i]. In this study, we show that Ca2+ ionophore, ionomycin, induced an immediate increase in intracellular free Ca2+ and examined how this increase affects heat shock response in rat hepatoma cell line H4II-E-C3. Results indicate that incubating H4II-E-C3 cells with 0.3 μM ionomycin at 37°C for 15 min results in the induction of HSP 70 in both Ca2+-containing and Ca2+-free medium. Associated with this increase in free Ca2+ is an in vivo change in membrane organization and activation of signaling molecules like ERKS and SAPKs/JNK. In Ca2+ containing medium HSP 70 induction mediated by HSF–HSE interaction was faster upon ionomycin treatment as compared to heat shock. Our results show that ionomycin, at sub lethal concentration, increases intracellular free Ca2+ concentration, activates SAPK/JNK and HSF–HSE interaction, and induces HSP 70 synthesis. J. Cell. Biochem. 86: 154–161, 2002. © 2002 Wiley-Liss, Inc.