Radford N B, Fina M, Benjamin I J, Moreadith R W, Graves K H, Zhao P, Gavva S, Wiethoff A, Sherry A D, Malloy C R, Williams R S
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2339-42. doi: 10.1073/pnas.93.6.2339.
Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart.
热休克蛋白被认为可限制多种环境应激所导致的损伤，但在脊椎动物中，这种细胞保护功能的直接代谢证据在很大程度上仅限于对培养细胞的研究。我们构建了转基因小鼠品系，使其在心肌中组成性表达人70-kDa热休克蛋白。从这些动物分离出的心脏显示，在经历足以诱导同窝非转基因小鼠心脏这些变量持续异常的短暂全心缺血后，高能磷酸储存的恢复增强，代谢性酸中毒得到纠正。这些数据证明了70-kDa热休克蛋白对增强完整心脏缺血后恢复具有直接的心脏保护作用。
