File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Role of the atypical protein kinase Cζ in regulation of 5′-AMP-activated protein kinase in cardiac and skeletal muscle

TitleRole of the atypical protein kinase Cζ in regulation of 5′-AMP-activated protein kinase in cardiac and skeletal muscle
Authors
Keywords5′-adenosine monophosphate-activated protein kinase
5′-adenosine monophosphate-activated protein kinase kinase
Akt
Ischemia
Issue Date2009
Citation
American Journal of Physiology - Endocrinology and Metabolism, 2009, v. 297 n. 2, p. E349-E357 How to Cite?
AbstractDuring 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 Cζ (PKCζ) 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 PKCζ plays in regulating AMPK in cardiac and skeletal muscle. Cultures of H9c2 myocytes (cardiac) and C2C12 myotubes (skeletal muscle) were pretreated with a selective PKCζ pseudosubstrate peptide inhibitor and treated with various AMPK activating agents to determine whether PKCζ regulates AMPK. PKCζ activity was also examined in isolated working rat hearts subjected to ischemia. We show that PKCζ 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 PKCζ 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 PKCζ activity. Finally, we show that PKCζ 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 PKCζ. We conclude that PKCζ 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. Copyright © 2009 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/195855
ISSN
2023 Impact Factor: 4.2
2023 SCImago Journal Rankings: 1.479
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorUssher, JR-
dc.contributor.authorJaswal, JS-
dc.contributor.authorWagg, CS-
dc.contributor.authorArmstrong, HE-
dc.contributor.authorLopaschuk, DG-
dc.contributor.authorKeung, W-
dc.contributor.authorLopaschuk, GD-
dc.date.accessioned2014-03-19T01:46:10Z-
dc.date.available2014-03-19T01:46:10Z-
dc.date.issued2009-
dc.identifier.citationAmerican Journal of Physiology - Endocrinology and Metabolism, 2009, v. 297 n. 2, p. E349-E357-
dc.identifier.issn0193-1849-
dc.identifier.urihttp://hdl.handle.net/10722/195855-
dc.description.abstractDuring 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 Cζ (PKCζ) 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 PKCζ plays in regulating AMPK in cardiac and skeletal muscle. Cultures of H9c2 myocytes (cardiac) and C2C12 myotubes (skeletal muscle) were pretreated with a selective PKCζ pseudosubstrate peptide inhibitor and treated with various AMPK activating agents to determine whether PKCζ regulates AMPK. PKCζ activity was also examined in isolated working rat hearts subjected to ischemia. We show that PKCζ 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 PKCζ 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 PKCζ activity. Finally, we show that PKCζ 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 PKCζ. We conclude that PKCζ 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. Copyright © 2009 the American Physiological Society.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Physiology - Endocrinology and Metabolism-
dc.subject5′-adenosine monophosphate-activated protein kinase-
dc.subject5′-adenosine monophosphate-activated protein kinase kinase-
dc.subjectAkt-
dc.subjectIschemia-
dc.titleRole of the atypical protein kinase Cζ in regulation of 5′-AMP-activated protein kinase in cardiac and skeletal muscle-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpendo.00009.2009-
dc.identifier.pmid19625676-
dc.identifier.scopuseid_2-s2.0-68049115412-
dc.identifier.volume297-
dc.identifier.issue2-
dc.identifier.spageE349-
dc.identifier.epageE357-
dc.identifier.isiWOS:000268252700009-
dc.identifier.issnl0193-1849-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats