Molecular and Cellular PharmacologyModulation of the heat-induced activation of mitogen-activated protein (MAP) kinase by quercetin
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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
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2015, Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and TherapyThe effect of quercetin on pro-apoptotic activity of cisplatin in HeLa cells
2005, Biochemical PharmacologyCitation Excerpt :One is that quercetin inhibits Hsp72 expression at the level of transcription by preventing the Heat shock factors 1 and 2 (Hsf1 and Hsf2) binding to the conserved DNA sequence known as the Heat Shock Element (HSE) in the promoter region of hsp genes [51]. Other experiments indicate that quercetin acts on early events before Hsps synthesis, by blocking the additional modifications necessary for activation of Hsf, like post-translational phosphorylation or by causing conformational changes of the factor, and inhibiting its interactions with other DNA-binding proteins in the promoter region [52,53]. We cannot exclude that also localization of Hsp72 in cells may play a supplementary role in pro-apoptotic activity of quercetin.
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2002, Biochemical PharmacologyCitation Excerpt :One possible explanation suggests that quercetin inhibits Hsp expression at the level of transcription by preventing the Heat shock factor 1 and 2 (Hsf1 and Hsf2) binding to the conserved DNA sequence known as the Heat Shock Element (HSE) in the promoter region of hsp genes [11,15]. Other experiments have indicated that quercetin acts on early events before Hsp synthesis, by blocking the additional modifications necessary for activation of Hsf, like posttranslational phosphorylation or by causing conformational changes of the factor, and inhibiting its interactions with other DNA-binding proteins in the promoter region [6,18]. Diminished Hsp27 expression by quercetin can be also explained by the ability of studied flavonoid to inhibit the activity of Hsp25 kinase, an enzyme necessary for the activation of small heat shock proteins [33].
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