PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes

Richard C.X. Li, Peipei Ping, Jun Zhang, William B. Wead, Xinan Cao, Jiuming Gao, Yuting Zheng, Shuang Huang, Jiahuai Han, Roberto Bolli

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

We have previously shown that protein kinase C (PKC) nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) are essential signaling elements in ischemic preconditioning. In the present study, we examined whether activation of PKCε affects the activation ot NF-κB in cardiac myocytes and whether MAPKs are mediators of this signaling event. Activation of PKCε (+ 108% above control) in adult rabbit cardiomyocytes to a degree that has been previously shown to protect myocytes against hypoxic injury increased the DNA-binding activity of NF-κB (+164%) and activator protein (AP)-1 (+ 127%) but not that of Elk-1. Activation of PKCη did not have an effect on these transcription factors. Activation of PKCε also enhanced the phosphorylation activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH2-terminal kinases (JNKs). PKCε-induced activation of NF-κB and AP-1 was completely abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK kinase-4, indicating that both signaling pathways are necessary. Taken together, these data identify NF-κB and AP-1 as downstream targets of PKCε, thereby establishing a molecular link between activation of PKCε and activation of NF-κB and AP-1 in cardiomyocytes. The results further demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are essential mediators of this event.

Original languageEnglish (US)
Pages (from-to)H1679-H1689
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number4 48-4
DOIs
StatePublished - Jan 1 2000

Keywords

  • Activator protein-1
  • Nuclear factor-κB
  • Protein kinase Cε

ASJC Scopus subject areas

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

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    Li, R. C. X., Ping, P., Zhang, J., Wead, W. B., Cao, X., Gao, J., Zheng, Y., Huang, S., Han, J., & Bolli, R. (2000). PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes. American Journal of Physiology - Heart and Circulatory Physiology, 279(4 48-4), H1679-H1689. https://doi.org/10.1152/ajpheart.2000.279.4.h1679