Samali A, Robertson J D, Peterson E, Manero F, van Zeijl L, Paul C, Cotgreave I A, Arrigo A P, Orrenius S
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Cell Stress Chaperones. 2001 Jan;6(1):49-58. doi: 10.1379/1466-1268(2001)006<0049:hpmotc>2.0.co;2.
Enhanced cell survival and resistance to apoptosis during thermotolerance correlates with an increased expression of heat shock proteins (Hsps). Here we present additional evidence in support of the hypothesis that the induction of Hsp27 and Hsp72 during acquired thermotolerance in Jurkat T-lymphocytes prevents apoptosis. In thermotolerant cells, Hsp27 was shown to associate with the mitochondrial fraction, and inhibition of Hsp27 induction during thermotolerance in cells transfected with hsp27 antisense potentiated mitochondrial cytochrome c release after exposure to various apoptotic stimuli, despite the presence of elevated levels of Hsp72. Caspase activation and apoptosis were inhibited under these conditions. In vitro studies revealed that recombinant Hsp72 more efficiently blocked cytochrome c-mediated caspase activation than did recombinant Hsp27. A model is presented for the inhibition of apoptosis during thermotolerance in which Hsp27 preferentially blocks mitochondrial cytochrome c release, whereas Hsp72 interferes with apoptosomal caspase activation.
热耐受期间细胞存活率提高和对凋亡的抗性增强与热休克蛋白（Hsps）表达增加相关。在此，我们提供额外证据支持以下假说：Jurkat T淋巴细胞获得性热耐受过程中Hsp27和Hsp72的诱导可防止细胞凋亡。在热耐受细胞中，Hsp27显示与线粒体部分相关联，在用hsp27反义转染的细胞中，热耐受期间抑制Hsp27诱导会增强暴露于各种凋亡刺激后线粒体细胞色素c的释放，尽管Hsp72水平升高。在这些条件下，半胱天冬酶激活和细胞凋亡受到抑制。体外研究表明，重组Hsp72比重组Hsp27更有效地阻断细胞色素c介导的半胱天冬酶激活。本文提出了一个热耐受期间细胞凋亡抑制模型，其中Hsp27优先阻断线粒体细胞色素c释放，而Hsp72干扰凋亡小体半胱天冬酶激活。
