PHARMACOLOGICAL MODULATION OF HEAT-SHOCK FACTOR-1 BY ANTIINFLAMMATORY DRUGS RESULTS IN PROTECTION AGAINST STRESS-INDUCED CELLULAR-DAMAGE
PHARMACOLOGICAL MODULATION OF HEAT-SHOCK FACTOR-1 BY ANTIINFLAMMATORY DRUGS RESULTS IN PROTECTION AGAINST STRESS-INDUCED CELLULAR-DAMAGE
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DOI：
10.1073/pnas.92.16.7207
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发表时间：
1995-08-01
影响因子：
11.1
通讯作者：
MORIMOTO, RI
中科院分区：
文献类型：
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作者：
LEE, BS;CHEN, J;MORIMOTO, RI
热休克基因的激活由不同形式的环境和生理应激已牵连在许多人类疾病，包括缺血性损伤，再灌注损伤，感染，神经变性和炎症。热休克蛋白和分子伴侣水平的提高对急性致死性应激具有广泛的细胞保护作用。在这里，我们表明，强效消炎痛激活人热休克转录因子1（HSF 1）的DNA结合活性。可能与其药理学用途相关，吲哚美辛预处理降低了HSF 1激活的温度阈值，使得在本身不足的温度下可以获得完全的热休克反应。吲哚美辛和升高的温度的协同作用是生物学相关的，并且导致保护细胞免于暴露于细胞毒性条件。
The activation of heat shock genes by diverse forms of environmental and physiological stress has been implicated in a number of human diseases, including ischemic damage, reperfusion injury, infection, neurodegeneration, and inflammation. The enhanced levels of heat shock proteins and molecular chaperones have broad cytoprotective effects against acute lethal exposures to stress. Here, we show that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1). Perhaps relevant to its pharmacological use, indomethacin pretreatment lowers the temperature threshold of HSF1 activation, such that a complete heat shock response can be attained at temperatures that are by themselves insufficient. The synergistic effect of indomethacin and elevated temperature is biologically relevant and results in the protection of cells against exposure to cytotoxic conditions.