Document Detail


Suppression of 5'-AMP-activated protein kinase activity does not impair recovery of contractile function during reperfusion of ischemic hearts.
MedLine Citation:
PMID:  19429810     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of 5'-AMP-activated protein kinase (AMPK) may benefit the heart during ischemia-reperfusion by increasing energy production. While AMPK stimulates glycolysis, mitochondrial oxidative metabolism is the major source of ATP production during reperfusion of ischemic hearts. Stimulating AMPK increases mitochondrial fatty acid oxidation, but this is usually accompanied by a decrease in glucose oxidation, which can impair the functional recovery of ischemic hearts. To examine the relationship between AMPK and cardiac energy substrate metabolism, we subjected isolated working mouse hearts expressing a dominant negative (DN) alpha(2)-subunit of AMPK (AMPK-alpha(2) DN) to 20 min of global no-flow ischemia and 40 min of reperfusion with Krebs-Henseleit solution containing 5 mM [U-(14)C]glucose, 0.4 mM [9, 10-(3)H]palmitate, and 100 microU/ml insulin. AMPK-alpha(2) DN hearts had reduced AMPK activity at the end of reperfusion (82 +/- 9 vs. 141 +/- 7 pmol.mg(-1).min(-1)) with no changes in high-energy phosphates. Despite this, AMPK-alpha(2) DN hearts had improved recovery of function during reperfusion (14.9 +/- 0.8 vs. 9.4 +/- 1.4 beats.min(-1).mmHg.10(-3)). During reperfusion, fatty acid oxidation provided 44.0 +/- 2.8% of total acetyl-CoA in AMPK-alpha(2) DN hearts compared with 55.0 +/- 3.2% in control hearts. Since insulin can inhibit both AMPK activation and fatty acid oxidation, we also examined functional recovery in the absence of insulin. Functional recovery was similar in both groups despite a decrease in AMPK activity and a decreased reliance on fatty acid oxidation during reperfusion (66.4 +/- 9.4% vs. 85.3 +/- 4.3%). These data demonstrate that the suppression of cardiac AMPK activity does not produce an energetically compromised phenotype and does not impair, but may in fact improve, the recovery of function after ischemia.
Authors:
Clifford D L Folmes; Cory S Wagg; Mei Shen; Alexander S Clanachan; Rong Tian; Gary D Lopaschuk
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-08
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  297     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-30     Completed Date:  2009-08-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H313-21     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Group and Department of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / metabolism,  physiology
Acetyl Coenzyme A / metabolism
Adenine Nucleotides / metabolism
Aerobiosis
Animals
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
Energy Metabolism / drug effects,  physiology
Enzyme Inhibitors / pharmacology
Fatty Acids, Nonesterified / metabolism
Glycogen / metabolism
Hypoglycemic Agents / pharmacology
Insulin / pharmacology
Mice
Myocardial Contraction / drug effects*
Myocardial Ischemia / metabolism,  physiopathology*
Myocardial Reperfusion Injury / metabolism,  physiopathology*
Palmitates / metabolism
Recovery of Function
Chemical
Reg. No./Substance:
0/Adenine Nucleotides; 0/Enzyme Inhibitors; 0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Palmitates; 11061-68-0/Insulin; 72-89-9/Acetyl Coenzyme A; 9005-79-2/Glycogen; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/AMPK alpha2 subunit, mouse; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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