Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids
Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids
复制标题
黄酮类化合物对体内外热休克因子激活的抑制作用
DOI：
10.1128/mcb.12.8.3490-3498.1992
复制
发表时间：
1992
影响因子：
5.3
通讯作者：
K. Nagata
中科院分区：
文献类型：
--
作者：
N. Hosokawa;K. Hirayoshi;H. Kudo;H. Takechi;A. Aoike;K. Kawai;K. Nagata
人类热休克蛋白(HSP)基因的转录激活受热休克因子(HSF)的激活调控。激活的HSF在翻译后获得DNA结合能力。我们以前报道过，在人类结肠癌的HeLa和Colo 320 DM细胞中，槲皮素和其他一些黄酮类化合物在mRNA积累水平上抑制了热休克蛋白的诱导。在这项研究中，我们用Colo 320 DM细胞提取物的凝胶迁移率改变分析，研究了槲皮素对HSP70启动子调控的氯霉素乙酰转移酶(CAT)活性的诱导以及HSF与热休克元件(HSE)结合的影响。在人HSP70基因启动子区域的调控下，将CAT基因导入COS-7和COLO 320 DM细胞后，槲皮素能抑制热诱导的CAT活性。在体内被热休克激活的全细胞提取液和体外被高温或尿素激活的细胞质提取液中，用槲皮素处理可抑制HSF与HSE的结合。体外激活的HSF的结合不受槲皮素的抑制。只有在体外热激活后的HSF与HSE的结合反应中才加入槲皮素，不能抑制HSF-HSE复合体的形成。因此，Quercetin与HSF相互作用，并通过抑制HSF的激活来抑制热休克后HSPs的诱导。
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.
影响因子：
56.9
作者：
PETERS, NK;FROST, JW;LONG, SR
通讯作者：
LONG, SR