Differential activation of mitogen-activated protein kinase cascades and apoptosis by protein kinase C ε and δ in neonatal rat ventricular myocytes

Maria C. Heidkamp, Allison L. Bayer, Jody L. Martin, Allen M. Samarel

Research output: Contribution to journalArticle

136 Scopus citations


Protein kinase C (PKC) ε and PKCδ translocation in neonatal rat ventricular myocytes (NRVMs) is accompanied by subsequent activation of the ERK, JNK, and p38MAPK cascades; however, it is not known if either or both novel PKCs are necessary for their downstream activation. Use of PKC inhibitors to answer this question is complicated by a lack of isoenzyme specificity, and the fact that many PKC inhibitors stimulate JNK and p38MAPK activity. Therefore, replication-defective adenoviruses (Advs) encoding constitutively active (ca) mutants of PKCε and PKCδ were used to test if either or both of these PKCs are sufficient to activate ERKs, JNKs, and/or p38MAPK in NRVMs. Adv-caPKCε infection (1 to 25 multiplicities of viral infection (MOI); 4 to 48 hours) increased total PKC-levels in a time- and dose-dependent manner, with maximal expression observed 8 hours after Adv infection. Adv-caPKCε induced a time- and dose-dependent increase in phosphorylated p42 and p44 ERKs, as compared with a control Adv encoding β-galactosidase (Adv-neβgal). Maximal ERK phosphorylation occurred 8 hours after Adv infection. In contrast, JNK was only minimally activated, and p38MAPK was relatively unaffected. Adv-caPKCδ infection (1 to 25 MOI, 4 to 48 hours) increased total PKCδ levels in a similar fashion. Adv-caPKCδ (5 MOI) induced a 29-fold increase in phosphorylated p54 JNK, and a 15-fold increase in phosphorylated p38MAPK 24 hours after Adv infection. In contrast, p42 and p44 ERK were only minimally activated. Whereas neither Adv induced NRVM hypertrophy, Adv-caPKCδ but not Adv-caPKCε induced NRVM apoptosis. We conclude that the novel PKCs differentially regulate MAPK cascades and apoptosis in an isoenzyme-specific and time-dependent manner.

Original languageEnglish (US)
Pages (from-to)882-890
Number of pages9
JournalCirculation research
Issue number10
StatePublished - Nov 9 2001



  • Adenovirus
  • Cardiomyocyte
  • Hypertrophy
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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