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Suppression of 5'-AMP-activated protein kinase activity does not impair recovery of contractile function during reperfusion of ischemic hearts.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2009 Jul; Vol. 297 (1), pp. H313-21. Date of Electronic Publication: 2009 May 08. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- AMP-Activated Protein Kinases metabolism
AMP-Activated Protein Kinases physiology
Acetyl Coenzyme A metabolism
Adenine Nucleotides metabolism
Aerobiosis
Animals
Energy Metabolism drug effects
Energy Metabolism physiology
Enzyme Inhibitors pharmacology
Fatty Acids, Nonesterified metabolism
Glycogen metabolism
Hypoglycemic Agents pharmacology
In Vitro Techniques
Insulin pharmacology
Mice
Myocardial Ischemia metabolism
Myocardial Reperfusion Injury metabolism
Palmitates metabolism
Recovery of Function
Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors
Myocardial Contraction drug effects
Myocardial Ischemia physiopathology
Myocardial Reperfusion Injury physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 297
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 19429810
- Full Text :
- https://doi.org/10.1152/ajpheart.01298.2008