Stress-activated protein kinase phosphorylation during cardioprotection in the ischemic myocardium

Ryan M. Fryer, Hemal H. Patel, Anna K. Hsu, Garrett J. Gross
2001 American Journal of Physiology. Heart and Circulatory Physiology  
Stress-activated protein kinase phosphorylation during cardioprotection in the ischemic myocardium. Am J Physiol Heart Circ Physiol 281: H1184-H1192, 2001.-Stress-activated protein kinases may be essential to cardioprotection. We assessed the role of p38 in an in vivo rat model of ischemia-reperfusion. Ischemic preconditioning (IPC) and the ␦ 1-opioid receptor agonist 2-methyl-4a␣-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a␣-octahydroquinolino [2,3,3-g]isoquinoline (TAN-67) significantly reduced
more » ... cantly reduced infarct size (IS), expressed as a percentage of the area at risk (AAR), versus animals subjected only to 30 min of ischemia and 2 h of reperfusion (7.1 Ϯ 1.5 and 29.6 Ϯ 3.3 vs. 59.7 Ϯ 1.6%). The p38 antagonist SB-203580 attenuated IPC when it was administered before (34.0 Ϯ 6.9%) or after (25.0 Ϯ 3.8%) the IPC stimulus; however, it did not significantly attenuate TAN-67-induced cardioprotection (39.6 Ϯ 3.2). We also assessed the phosphorylation of p38 and c-jun NH 2-terminal kinase (JNK) throughout ischemiareperfusion in nuclear and cytosolic fractions. After either intervention, no increase was detected in the phosphorylation state of either enzyme in the nuclear fraction or for p38 in the cytosolic fraction versus control hearts. However, there was a robust increase in JNK activity in the cytosolic fraction immediately on reperfusion that was more pronounced in animals subjected to IPC or administered TAN-67. These data suggest that SB-203580 likely attenuates IPC via the inhibition of kinases other than p38, which may include JNK. The data also suggest that activation of JNK during early reperfusion may be an important component of cardioprotection. preconditioning; opioid; mitogen-activated protein kinase; p38; c-jun NH 2-terminal kinase
doi:10.1152/ajpheart.2001.281.3.h1184 pmid:11514286 fatcat:3tmqt6jzb5glxh7fs6o5fauml4