ACTIVATION OF THE HEAT-SHOCK TRANSCRIPTION FACTOR BY HYPOXIA IN MAMMALIAN-CELLS
ACTIVATION OF THE HEAT-SHOCK TRANSCRIPTION FACTOR BY HYPOXIA IN MAMMALIAN-CELLS
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DOI：
10.1073/pnas.87.16.6263
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发表时间：
1990-08-01
影响因子：
11.1
通讯作者：
WILLIAMS, RS
中科院分区：
文献类型：
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作者：
BENJAMIN, IJ;KROGER, B;WILLIAMS, RS
应激蛋白家族的成员如HSP 70在缺血组织中被诱导，并可能有助于细胞在短暂性循环功能不全发作中存活的能力。然而，导致这种诱导的生化事件，以及它们与热应激引发的途径的相似程度，尚未确定。在这项研究中，我们表明，短暂暴露培养的C2C12小鼠肌源性细胞缺氧的气氛刺激DNA结合活性的热休克转录因子通过机制，是独立的新的蛋白质合成。缺氧细胞中热休克转录因子的激活与内源性HSP70基因转录的诱导和由人HSP70启动子控制的异源报告基因的诱导在时间上相关。此外，缺氧诱导人HSP 70启动子需要一个完整的热休克元件，这表明该复杂启动子中包含的其他顺式作用转录控制元件不足以抑制缺氧细胞内产生的信号。这些发现提供了强有力的证据表明，缺氧和热休克诱导HSP 70基因的表达相似，如果不是相同的，机制。
Members of the stress protein family such as HSP70 are induced in ischemic tissues and may contribute to the ability of cells to survive episodes of transient circulatory insufficiency. However, the biochemical events that lead to this induction, and their degree of similarity with pathways triggered by heat stress, have not been defined. In this study, we demonstrate that transient exposure of cultured C2C12 mouse myogenic cells to a hypoxic atmosphere stimulates DNA binding activity of the heat shock transcription factor through mechanisms that are independent of new protein synthesis. Activation of heat shock transcription factor in hypoxic cells is temporally associated with induction of endogenous HSP70 gene transcription and with induction of a heterologous reporter gene controlled by the human HSP70 promoter. Furthermore, induction of the human HSP70 promoter by hypoxia requires an intact heat shock element, indicating that other cis-acting transcriptional control elements contained within this complex promoter are not sufficient to transduce signals generated within hypoxic cells. These findings provide strong evidence that hypoxia and heat shock induce expression of the HSP70 gene by similar, if not identical, mechanisms.