PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits

Peipei Ping, Jun Zhang, Shuang Huang, Xinan Cao, Xian Liang Tang, Richard C.X. Li, Yu Ting Zheng, Yumin Qiu, Angela Clerk, Peter Sugden, Jiahuai Han, Roberto Bolli

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

A conscious rabbit model was used to study the effect of ischemic preconditioning (PC) on stress-activated kinases [c-Jun NH2-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (MAPK)] in an environment free of surgical trauma and attending external stress. Ischemic PC (6 cycles of 4-min ischemia/4-min reperfusion) induced significant activation of protein kinase C (PKC)-ε in the particulate fraction, which was associated with activation of p46 JNK in the nuclear fraction and p54 JNK in the cytosolic fraction; all of these changes were completely abolished by the PKC inhibitor chelerythrine. Selective enhancement of PKC-ε activity in adult rabbit cardiac myocytes resulted in enhanced activity of p46/p54 JNKs, providing direct in vitro evidence that PKC-ε is coupled to both kinases. Studies in rabbits showed that the activation of p46 JNK occurred during ischemia, whereas that of p54 JNK occurred after reperfusion. A single 4-min period of ischemia induced a robust activation of the p38 MAPK cascade, which, however, was attenuated after 5 min of reperfusion and disappeared after six cycles of 4-min ischemia/reperfusion. Overexpression of PKC-ε in cardiac myocytes failed to increase the p38 MAPK activity. These results demonstrate that ischemic PC activates p46 and p54 JNKs via a PKC-ε- dependent signaling pathway and that there are important differences between p46 and p54 JNKs with respect to the subcellular compartment (cytosolic vs. nuclear) and the mechanism (ischemia vs. reperfusion) of their activation after ischemic PC.

Original languageEnglish (US)
Pages (from-to)H1771-H1785
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number5 46-5
DOIs
StatePublished - Nov 1999

Keywords

  • C-Jun NH-terminal kinases
  • Ischemia-reperfusion
  • P38 mitogen-activated protein kinases
  • Protein kinase C
  • Stress-activated protein kinases

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Ping, P., Zhang, J., Huang, S., Cao, X., Tang, X. L., Li, R. C. X., Zheng, Y. T., Qiu, Y., Clerk, A., Sugden, P., Han, J., & Bolli, R. (1999). PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits. American Journal of Physiology - Heart and Circulatory Physiology, 277(5 46-5), H1771-H1785. https://doi.org/10.1152/ajpheart.1999.277.5.h1771