Sakamoto K, Urushidani T, Nagao T
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 3-1 Hongo 7-chome, Bunkyo-ku, Tokyo, 113-0033, Japan.
Biochem Biophys Res Commun. 2000 Mar 5;269(1):137-42. doi: 10.1006/bbrc.2000.2233.
We investigated the role of the 27-kDa heat shock protein (HSP27) in cardiac protection using Langendorff-perfused rat hearts. After preconditioning (a single episode of 5 min global ischemia followed by 5 min of reperfusion), HSP27 redistributed from the cytosol to the sarcomere and recovery of the contractile function, after 40 min of global ischemia and 50 min of reperfusion, was significantly enhanced. Both SB203580, a p38 MAP kinase inhibitor, and bisindolylmaleimide I, a protein kinase C inhibitor, prevented the effects of preconditioning. Both 2-chloro-N(6)-cyclopentyladenosine (adenosine A1 agonist) and anisomycin (activator of p38 MAP kinase and c-jun N-terminal kinase) mimicked preconditioning. These results suggest that activation of protein kinase C followed by activation of p38 MAP kinase elicits translocation of HSP27 to the sarcomere, a process which may be involved in the cardioprotective mechanism afforded by ischemic preconditioning in rat heart.
我们利用Langendorff灌注大鼠心脏研究了27 kDa热休克蛋白（HSP27）在心脏保护中的作用。预处理（5分钟全心缺血，随后5分钟再灌注）后，HSP27从胞质溶胶重新分布到肌节，并且在40分钟全心缺血和50分钟再灌注后，收缩功能的恢复显著增强。p38丝裂原活化蛋白激酶抑制剂SB203580和蛋白激酶C抑制剂双吲哚马来酰亚胺I均能阻止预处理的作用。2-氯-N(6)-环戊基腺苷（腺苷A1激动剂）和茴香霉素（p38丝裂原活化蛋白激酶和c-jun氨基末端激酶激活剂）均能模拟预处理。这些结果表明，蛋白激酶C激活后p38丝裂原活化蛋白激酶的激活引发HSP27向肌节的转位，这一过程可能参与了大鼠心脏缺血预处理提供的心脏保护机制。
