| Autor: |
Ji Li, Coven, David L., Miller, Edward J., Xiaoyue Hu, Young, Martin E., Carling, David, Sinusas, Albert J., Young, Lawrence H. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Oct2006, Vol. 291 Issue 4, pH1927-H1934, 8p, 1 Diagram, 1 Chart, 4 Graphs |
| Abstrakt: |
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 α-subunits and regulatory β- and γ-subunits with multiple isoforms. Mutations in the cardiac α2-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 α- and γ-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated α1-isoform (6-fold, P < 0.01) and α2-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of α-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory γ1- and γ2-isoforms were expressed in the heart. Theγ1 and α2-isoforms coimmunoprecipitated with α1- and α2-isoforms in proportion to α-subunit content. γ1-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation (Thr172) in hearts. Ischemia similarly increased AMPK activity associated with the γ1- and γ2-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic α1- and α2-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory γ1- or γ2-isoforms to which they are complexed. Despite the pathophysiological importance of γ2-isoform mutations, γ1-isoform complexes account for most of the AMPK activity in the ischemic heart. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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