Arachidonate is a potent modulator of human heat shock gene transcription.
Arachidonate is a potent modulator of human heat shock gene transcription.
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花生四烯酸是人类热休克基因转录的有效调节剂。
DOI：
10.1073/pnas.91.6.2280
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发表时间：
1994
影响因子：
11.1
通讯作者：
Morimoto,RI
中科院分区：
文献类型：
--
作者：
Jurivich,DA;Sistonen,L;Sarge,KD;Morimoto,RI
细胞和组织损伤通过花生四烯酸及其代谢物的作用激活炎症反应，导致急性期蛋白和炎性细胞因子的表达。在分子水平上，花生四烯酸如何调节炎症反应知之甚少。由于炎症也与局部组织温度升高有关，我们研究了花生四烯酸是否直接参与热休克反应。细胞外暴露于花生四烯酸诱导热休克基因转录的剂量依赖性的方式通过收购的DNA结合活性和磷酸化的热休克因子1（HSF 1）。此外，将细胞暴露于低浓度的花生四烯酸（其本身不诱导HSF 1 DNA结合活性），将HSF 1活化的温度阈值从与生理学无关的升高的温度（> 42 ℃）降低到在发热反应期间可以达到的温度（39-40 ℃）。这些结果表明，升高的热休克基因表达是花生四烯酸介导的细胞反应的直接后果。
Cell and tissue injury activate the inflammatory response through the action(s) of arachidonic acid and its metabolites, leading to the expression of acute-phase proteins and inflammatory cytokines. At the molecular level, little is known how arachidonic acid regulates the inflammatory response. As inflammation is also associated with local increase in tissue temperatures, we examined whether arachidonic acid was directly involved in the heat shock response. Extracellular exposure to arachidonic acid induced heat shock gene transcription in a dose-dependent manner via acquisition of DNA-binding activity and phosphorylation of heat shock factor 1 (HSF1). In addition, exposure of cells to low concentrations of arachidonic acid, which by themselves did not induce HSF1 DNA-binding activity, reduced the temperature threshold for HSF1 activation from elevated temperatures which are not physiologically relevant (> 42 degrees C) to temperatures which can be attained during the febrile response (39-40 degrees C). These results indicate that elevated heat shock gene expression is a direct consequence of an arachidonic acid-mediated cellular response.