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Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection: complex

T M Vondriska1, J Zhang, C Song

  • 1Department of Physiology, Division of Cardiology, University of Louisville, Louisville, KY, USA.

Circulation Research
|June 23, 2001
PubMed

Insights

Protein kinase C epsilon (PKCepsilon) and Src tyrosine kinase form functional signaling modules crucial for nitric oxide (NO)-induced late preconditioning. Inhibiting PKC blocked this cardioprotection, module formation, and Src activity.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Signal Transduction

Background:

  • Protein kinase C epsilon (PKCepsilon) plays a key role in cardioprotection.
  • The specific signaling mechanisms underlying this protective phenotype are not well understood.
  • Signal transduction pathways may involve the formation of multiprotein signaling complexes.

Purpose of the Study:

  • To investigate if multiprotein complex assembly mediates signaling in cardioprotection.
  • To characterize the association between PKCepsilon and Src tyrosine kinase in NO-induced late preconditioning.
  • To determine the functional role of the PKCepsilon-Src module in cardioprotection.

Main Methods:

  • Experiments were conducted in a conscious rabbit model of NO-induced late preconditioning.
  • Characterized associations between PKCepsilon and Src tyrosine kinase.
  • Assessed Src activity in response to PKCepsilon.
  • Utilized recombinant adenoviruses to deliver PKCepsilon into adult cardiac cells.
  • Investigated the effects of PKC inhibition on cardioprotection and module formation.

Main Results:

  • PKCepsilon and Src form functional signaling modules in vitro, with PKCepsilon activating Src.
  • PKCepsilon delivery via adenovirus increased Src activity in cardiac cells.
  • NO-induced late preconditioning involved PKCepsilon-Src module formation and enhanced Src activity.
  • PKC inhibition abolished cardioprotection, PKCepsilon-Src module formation, and associated Src activity.

Conclusions:

  • The PKCepsilon-Src module is functionally involved in NO-induced late preconditioning.
  • Formation of this signaling module is essential for orchestrating cardioprotection in rabbits.
  • This study elucidates a key signaling architecture in a critical aspect of cardiovascular protection.

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