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首页> 外文期刊>Molecular and Cellular Biology >Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids.
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Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids.

机译：黄酮类化合物在体内和体外抑制热休克因子的激活。

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Transcriptional activation of human heat shock protein (HSP) genes by heat shock or other stresses is regulated by the activation of a heat shock factor (HSF). Activated HSF posttranslationally acquires DNA-binding ability. We previously reported that quercetin and some other flavonoids inhibited the induction of HSPs in HeLa and COLO 320DM cells, derived from a human colon cancer, at the level of mRNA accumulation. In this study, we examined the effects of quercetin on the induction of HSP70 promoter-regulated chloramphenicol acetyltransferase (CAT) activity and on the binding of HSF to the heat shock element (HSE) by a gel mobility shift assay with extracts of COLO 320DM cells. Quercetin inhibited heat-induced CAT activity in COS-7 and COLO 320DM cells which were transfected with plasmids bearing the CAT gene under the control of the promoter region of the human HSP70 gene. Treatment with quercetin inhibited the binding of HSF to the HSE in whole-cell extracts activated in vivo by heat shock and in cytoplasmic extracts activated in vitro by elevated temperature or by urea. The binding of HSF activated in vitro by Nonidet P-40 was not suppressed by the addition of quercetin. The formation of the HSF-HSE complex was not inhibited when quercetin was added only during the binding reaction of HSF to the HSE after in vitro heat activation. Quercetin thus interacts with HSF and inhibits the induction of HSPs after heat shock through inhibition of HSF activation.
机译：通过热休克因子（HSF）的激活来调节热休克或其他应激对人类热休克蛋白（HSP）基因的转录激活。活化的HSF在翻译后获得DNA结合能力。我们以前曾报道过槲皮素和其他一些类黄酮在人类积聚癌的HeLa和COLO 320DM细胞中在mRNA积累水平上抑制了HSP的诱导。在这项研究中，我们通过用COLO 320DM细胞提取物进行的凝胶迁移率移动试验研究了槲皮素对HSP70启动子调节的氯霉素乙酰转移酶（CAT）活性的诱导以及对HSF与热休克元件（HSE）结合的影响。 。槲皮素抑制了COS-7和COLO 320DM细胞中热诱导的CAT活性，所述COS-7和COLO 320DM细胞在人HSP70基因启动子区的控制下被带有CAT基因的质粒转染。用槲皮素处理抑制了热激在体内激活的全细胞提取物中以及高温或尿素在体外激活的细胞质提取物中HSF与HSE的结合。加入槲皮素未抑制Nonidet P-40在体外激活的HSF结合。当仅在体外热活化后HSF与HSE的结合反应期间加入槲皮素时，HSF-HSE复合物的形成未被抑制。槲皮素因此与HSF相互作用，并通过抑制HSF活化来抑制热休克后HSP的诱导。

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