RGD Reference Report - Activation of AMPK alpha- and gamma-isoform complexes in the intact ischemic rat heart. - Rat Genome Database

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Activation of AMPK alpha- and gamma-isoform complexes in the intact ischemic rat heart.

Authors: Li, J  Coven, DL  Miller, EJ  Hu, X  Young, ME  Carling, D  Sinusas, AJ  Young, LH 
Citation: Li J, etal., Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1927-34. Epub 2006 Apr 28.
RGD ID: 1600447
Pubmed: (View Article at PubMed) PMID:16648175
DOI: Full-text: DOI:10.1152/ajpheart.00251.2006

AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple isoforms. Mutations in the cardiac gamma(2)-isoform have been associated with hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological regulation of AMPK complexes containing different subunit isoforms is not well defined and is important for an understanding of the function of this signaling pathway in the intact heart. We evaluated the kinase activity associated with heart AMPK complexes containing specific alpha- and gamma-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated alpha(1)-isoform (6-fold, P < 0.01) and alpha(2)-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of alpha-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory gamma(1)- and gamma(2)-isoforms were expressed in the heart. The gamma(1)- and gamma(2)-isoforms coimmunoprecipitated with alpha(1)- and alpha(2)-isoforms in proportion to alpha-subunit content. gamma(1)-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation (Thr(172)) in hearts. Ischemia similarly increased AMPK activity associated with the gamma(1)- and gamma(2)-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic alpha(1)- and alpha(2)-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory gamma(1)- or gamma(2)-isoforms to which they are complexed. Despite the pathophysiological importance of gamma(2)-isoform mutations, gamma(1)-isoform complexes account for most of the AMPK activity in the ischemic heart.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Prkaa1  (protein kinase AMP-activated catalytic subunit alpha 1)
Prkaa2  (protein kinase AMP-activated catalytic subunit alpha 2)
Prkab1  (protein kinase AMP-activated non-catalytic subunit beta 1)
Prkab2  (protein kinase AMP-activated non-catalytic subunit beta 2)
Prkag1  (protein kinase AMP-activated non-catalytic subunit gamma 1)
Prkag2  (protein kinase AMP-activated non-catalytic subunit gamma 2)


Additional Information