Translocation of HSP27 to sarcomere induced by ischemic preconditioning in isolated rat hearts.
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.
Sakamoto
K
K
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 3-1 Hongo 7-chome, Bunkyo-ku, Tokyo, 113-0033, Japan.
Urushidani
T
T
Nagao
T
T
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins; D006321:Heart / Q000187:drug effects; D006360:Heat-Shock Proteins; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases; D009206:Myocardium / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010477:Perfusion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D009363:Neoplasm Proteins; D011725:Pyridines; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; C093642:SB 203580