Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase Cε, but not p42/44MAPK

Susan Wilson, Wu Song, Kaszala Karoly, Tanya Ravingerova, Agnes Vegh, Juluisby Papp, Shogo Tomisawa, James R. Parratt, Nigel J. Pyne

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKCε and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence that p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKCε to cell membranes, a response that is sustained for up to 4 h. However, PKCε is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKCε is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKCε from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKCε mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKCε persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKCε.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalMolecular and Cellular Biochemistry
Volume160-161
DOIs
Publication statusPublished - Oct 19 1996

Keywords

  • Classical preconditioning
  • Heat shock proteins
  • Immediate early genes
  • Noradrenaline
  • Nuclear transcription
  • P42/44MAPK
  • Protein kinase Cε

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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