Giffard Rona G, Yenari Midori A
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA.
J Neurosurg Anesthesiol. 2004 Jan;16(1):53-61. doi: 10.1097/00008506-200401000-00010.
Overexpression of inducible Hsp70 has been shown to provide protection from cerebral ischemia both in animal models of stroke and in cell culture models. New work suggests that there are multiple routes of cell death, including apoptotic and necrotic cell death. Hsp70 is known to protect from both necrotic and apoptotic cell death. In addition to the well-studied role of Hsp70 as a molecular chaperone assisting in correct protein folding, several new mechanisms by which Hsp70 can prevent cell death have been described. Hsp70 is now known to regulate apoptotic cell death both directly by interfering with the function of several proteins that induce apoptotic cell death as well as indirectly by increasing levels of the anti-death protein bcl-2. Despite these new insights into the ways in which Hsp70 functions as an anti-death protein, further surprises are likely as we continue to gain insight into the functioning of this multifaceted protein.
在中风的动物模型和细胞培养模型中,诱导型Hsp70的过表达已被证明能为大脑缺血提供保护。新的研究表明,细胞死亡有多种途径,包括凋亡性和坏死性细胞死亡。已知Hsp70能保护细胞免受坏死性和凋亡性细胞死亡。除了作为分子伴侣协助正确蛋白质折叠这一已被充分研究的作用外,还描述了Hsp70预防细胞死亡的几种新机制。现在已知Hsp70通过直接干扰几种诱导凋亡性细胞死亡的蛋白质的功能以及间接增加抗死亡蛋白bcl-2的水平来调节凋亡性细胞死亡。尽管对Hsp70作为抗死亡蛋白的作用方式有了这些新的认识,但随着我们继续深入了解这种多面蛋白的功能,可能还会有更多惊喜。