Joyeux, M; Boumendjel, A; Carroll, R; Ribuot, C; Godin-Ribuot, D; Yellon, DM; (2000) SB 203580, a mitogen-activated protein kinase inhibitor, abolishes resistance to myocardial infarction induced by heat stress. CARDIOVASC DRUG THER , 14 (3) 337 - 343.
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Heat stress (HS) is known to confer protection against ischemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the mechanisms involved in this cardioprotection are yet to be elucidated. Mitogen-activated protein (MAP) kinase cascades have been demonstrated to be involved in cellular response to different stresses. In particular, p38 MAP kinase is known to be activated by HS. Therefore, we investigated the implication of this kinase in HS-induced resistance to myocardial infarction, in the isolated rat heart model, using SB 203580 (SB) to selectively inhibit p38 MAP kinase. Rats were treated with SB (2.83 mg/kg, i.p.) or vehicle (1% DMSO in saline, i.p.) before they were either heat stressed (42 degrees C for 15 minutes) or sham anesthetized. Their hearts were isolated 24 hours later, retrogradely perfused, and subjected to a 35-minute occlusion of the left coronary artery followed by 120 minutes of reperfusion. The infarct-to-risk ratio was significantly reduced in HS (16.9 +/- 2.0%) compared with sham (41.6 +/- 2.5%) hearts. This reduction in infarct size was abolished in the SB 203580-treated group (37.8 +/- 1.9% in HS + SB vs. 42.0 +/- 1.9% in sham + SB). Risk zones were similar between experimental groups. Western blot analysis of the myocardial HSP72 showed an HS-induced increase of this protein, which was not modified by the p38 MAP kinase inhibitor, SB 203580. We conclude that activation of p38 MAP kinase appears to play a role in the functional cardioprotection associated with the heat stress response, which seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the p38 MAP kinase and heat stress proteins in this adaptative response.
|Title:||SB 203580, a mitogen-activated protein kinase inhibitor, abolishes resistance to myocardial infarction induced by heat stress|
|Keywords:||heat stress, infarct size, mitogen-activated protein kinase, SB 203580, heat stress protein, ISCHEMIA-REPERFUSION INJURY, MAP KINASE, RAT HEARTS, DELAYED PROTECTION, SHOCK PROTEINS, IN-VIVO, PHOSPHORYLATION, INDUCTION, RABBIT, LIPOPOLYSACCHARIDE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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