Kagaya A, Okada A, Jitsuiki H, Tawara Y, Inagaki M, Takebayashi M, Saeki T, Nishida A, Nakata Y, Yamawaki S
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
J Neural Transm (Vienna). 2000;107(8-9):919-29. doi: 10.1007/s007020070042.
This study was conducted to investigate an effect of heat stress at 44 degrees C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.
本研究旨在探讨44℃热应激30分钟对细胞内Ca2+信号系统及热休克蛋白（HSP）-70表达的影响。热应激后1小时、3小时和6小时，5-羟色胺（5-HT）诱导的Ca2+动员减少，热应激后12小时和24小时恢复至对照水平。热应激1小时后，无论5-HT浓度如何，刺激细胞时Ca2+升高均显著降低。热应激1小时后，凝血酶诱导的Ca2+增加也明显减少。热应激后6小时和9小时，HSP-70水平升高。在热休克蛋白合成抑制剂槲皮素处理的细胞中，热应激后HSP-70表达未增强，且对5-HT的Ca2+升高未恢复至对照水平。然而，在暴露于天冬氨酸-谷氨酸-缬氨酸-天冬氨酸-组氨酸（DEVD）的细胞中，应激后5-HT诱导的Ca2+升高未恢复至对照水平，而DEVD对热应激诱导的HSP-70合成影响不大。地塞米松未改变热应激后HSP-70表达或Ca2+反应的变化。这些结果表明，热应激减弱了5-HT诱导的Ca2+动员，且HSP-70表达可能通过C6细胞中的蛋白酶活性在Ca2+损伤恢复中起重要作用。
