Benjamin I J, McMillan D R
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas 75235-8573, USA.
Circ Res. 1998 Jul 27;83(2):117-32. doi: 10.1161/01.res.83.2.117.
How a cell responds to stress is a central problem in cardiovascular biology. Diverse physiological stresses (eg, heat, hemodynamics, mutant proteins, and oxidative injury) produce multiple changes in a cell that ultimately affect protein structures and function. Cells from different phyla initiate a cascade of events that engage essential proteins, the molecular chaperones, in decisions to repair or degrade damaged proteins as a defense strategy to ensure survival. Accumulative evidence indicates that molecular chaperones such as the heat shock family of stress proteins (HSPs) actively participate in an array of cellular processes, including cytoprotection. The versatility of the ubiquitous HSP family is further enhanced by stress-inducible regulatory networks, both at the transcriptional and posttranscriptional levels. In the present review, we discuss the regulation and function of HSP chaperones and their clinical significance in conditions such as cardiac hypertrophy, vascular wall injury, cardiac surgery, ischemic preconditioning, aging, and, conceivably, mutations in genes encoding contractile proteins and ion channels.
细胞如何应对应激是心血管生物学中的核心问题。多种生理应激(如热、血流动力学、突变蛋白和氧化损伤)会在细胞内产生多种变化,最终影响蛋白质的结构和功能。来自不同门的细胞会启动一系列事件,使必需蛋白——分子伴侣参与到修复或降解受损蛋白的决策中,作为确保生存的防御策略。越来越多的证据表明,诸如应激蛋白热休克家族(HSPs)等分子伴侣积极参与一系列细胞过程,包括细胞保护。无处不在的HSP家族的多功能性在转录和转录后水平上通过应激诱导的调控网络进一步增强。在本综述中,我们讨论了HSP伴侣的调控和功能及其在诸如心肌肥大、血管壁损伤、心脏手术、缺血预处理、衰老等情况下的临床意义,以及可以想象的在编码收缩蛋白和离子通道的基因突变中的临床意义。