HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ussher, J. R. Articles by Lopaschuk, G. D. Search for Related Content PubMed PubMed Citation Articles by Ussher, J. R. Articles by Lopaschuk, G. D.

Role of the atypical protein kinase C in regulation of 5'-AMP-activated protein kinase in cardiac and skeletal muscle

Cardiovascular Research Group, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

Submitted 6 January 2009 ; accepted in final form 12 May 2009

During metabolic stress, phosphorylation and activation of 5'-AMP-activated protein kinase (AMPK) becomes a major regulator of cellular energy metabolism in heart and skeletal muscle. Despite this, the upstream regulation of AMPK in both heart and muscle is poorly understood. Recent work has implicated the atypical protein kinase C (PKC) as a regulator of AMPK in endothelial cells via phosphorylation of LKB1, an upstream AMPK kinase (AMPKK). Our goal was to determine the potential role PKC plays in regulating AMPK in cardiac and skeletal muscle. Cultures of H9c2 myocytes (cardiac) and C₂C₁₂ myotubes (skeletal muscle) were pretreated with a selective PKC pseudosubstrate peptide inhibitor and treated with various AMPK activating agents to determine whether PKC regulates AMPK. PKC activity was also examined in isolated working rat hearts subjected to ischemia. We show that PKC is not involved in regulating threonine 172 AMPK phosphorylation induced by metformin or phenformin in either cardiac or skeletal muscle cells but is involved in 5-aminoimidazole-4-carboxamine-1-β-D-ribofuranoside (AICAR)-induced AMPK phosphorylation in cardiac muscle cells. Activation of PKC with high palmitate concentrations is also insufficient to increase AMPK phosphorylation. Furthermore, we show that the ischemia-induced activation of AMPK is not accompanied by increased PKC activity. Finally, we show that PKC may actually be a downstream target of AMPK in skeletal muscle, since adenoviral expression of a dominant-negative mutant of AMPK prevented metformin- and AICAR-induced phosphorylation of PKC. We conclude that PKC plays a very minor role in the regulation of AMPK in cardiac and skeletal muscle and may actually be a downstream target of AMPK in skeletal muscle.

5'-adenosine monophosphate-activated protein kinase; 5'-adenosine monophosphate-activated protein kinase kinase; Akt; ischemia