Elsevier

Biochemical Pharmacology

Volume 56, Issue 9, 1 November 1998, Pages 1151-1155
Biochemical Pharmacology

Molecular and Cellular Pharmacology
Modulation of the heat-induced activation of mitogen-activated protein (MAP) kinase by quercetin

https://doi.org/10.1016/S0006-2952(98)00253-6Get rights and content

Abstract

Effects of quercetin, a bioflavonoid compound, on heat-induced activation of mitogen-activated protein (MAP) kinase in rat hepatoma (H4) cells were examined. Quercetin decreased cell viability and induced DNA fragmentation in heat-shocked H4 cells. MAP kinase in heat-shocked cells was activated and reached a peak at 1 hr after the heat shock, and then gradually decreased. Quercetin inhibited the heat-induced activation of MAP kinase observed at 1 hr after heat shock, but markedly stimulated MAP kinase activity at 4 hr after heat shock. Thus, quercetin modulated the heat-induced activation of MAP kinase in a biphasic manner. Present observations indicate that quercetin modulates protein phosphorylation, especially that controled by MAP kinase, in early events of heat shock response.

Section snippets

Cell culture and heat shock conditions

H4 cells were grown at 37° on tissue culture dishes with Swims-77S medium supplemented with 5% fetal bovine serum and 5% horse serum. At 1 hr before experimentation, the incubation medium was changed to Krebs–Ringer–HEPES buffer, pH 7.4, containing 132 mM NaCl, 4.8 mM KCl, 2.4 mM MgCl2, 0.1 mM EGTA, 1 mM CaCl2, 20 mM HEPES, 10 mM glucose, and 0.1% of BSA. For heat shock, 100-mm culture dishes were immersed in a water bath for 10 min at 45°. The cells (106 cells) were processed for assays at 0

Effects of heat shock and quercetin on H4 cell viability

We treated H4 cells at 45° for 10 min and then incubated them at 37° for 0–4 hr. As shown in Fig. 1, the viability of heat-shocked cells was comparable to that of control cells. Although treatment of cells with 0.1 mM quercetin alone slightly decreased cell viability, more than 90% of the cells survived for the 4-hr incubation at 37°. In the presence of 0.1 mM quercetin, the viability of heat-shocked cells rapidly decreased to 75% of control cells within the 2-hr incubation at 37° after heat

Discussion

Quercetin was reported to be a hyperthermic sensitizer in HeLa cells [13]. Quercetin has various biological activities: the inhibition of cultured cell growth [13], inhibitory effects on glycolysis [24], macromolecule synthesis [25], and the activity of protein kinases [19] and ATPases [26]. Furthermore, quercetin was reported to inhibit HSF activity and HSP synthesis at the transcriptional level 15, 16, 17. Because the synthesis of HSPs is a major event in heat shock responses, the inhibition

References (27)

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