Activation of stress response by lonomycin 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 muM ionomycin at 37degreesC 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. (C) 2002 Wiley-Liss, Inc.