PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation

被引:14
作者
Mockridge, JW
Punn, A
Latchman, DS
Marber, MS
Heads, RJ
机构
[1] St Thomas Hosp, Rayne Inst, Univ London Kings Coll, Dept Cariol, London SE1 7EH, England
[2] Inst Child Hlth, London WC1N 1EH, England
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2000年 / 279卷 / 02期
关键词
cytoprotection; mitogen-activated protein kinases; extracellular signal-regulated kinases; p38; protein kinase C; cardiomyocytes;
D O I
10.1152/ajpheart.2000.279.2.H492
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In this study we used an in vitro model of delayed preconditioning to investigate activation of mitogen-activated protein kinases (MAPKs) and their potential role in protection. Neonatal rat cardiomyocytes were preconditioned using a buffer containing glycolytic inhibitors and low pH (minimal metabolic preconditioning; MMPC) consisting of modified Krebs buffer, 10 mM 2-deoxy-glucose, and 20 mM lactate, pH 6.8, for 2 h followed by 24 h of simulated reperfusion before lethal simulated ischemia (LSI). MAPK activation during the MMPC protocol was determined using phospho-specific antisera and the effect on protection determined following LSI. Rapid, transient phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 MAPK was observed during each of the MMPC, reperfusion, and LSI phases; an effect blocked by MAPK inhibitors PD-98059 and SB-203580, respectively, but not by the protein kinase C (PKC) inhibitor Ro31-8220. However, although MMPC was blocked by Ro31-8220, treatment with the MAPK inhibitors during the preconditioning protocol did not block delayed protection conferred by MMPC. Thus the data suggest that, in this model of delayed preconditioning, protection appears to be PKC dependent but independent of ERK1/2 or p38 MAPK activation.
引用
收藏
页码:H492 / H501
页数:10
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