Medical College of Wisconsin
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Metabolic adaptation of the hypertrophied heart: role of the malate/aspartate and alpha-glycerophosphate shuttles. J Mol Cell Cardiol 2000 Dec;32(12):2287-97

Date

12/13/2000

Pubmed ID

11113004

DOI

10.1006/jmcc.2000.1257

Scopus ID

2-s2.0-0034509885   29 Citations

Abstract

Activation of the malate/aspartate and alpha -glycerophosphate shuttles (the NADH shuttles) has been identified in glycolytically active newborn myocardium. The goal of this study was to determine if the NADH shuttles and their regulatory genes are activated in hypertrophied myocardium as substrate utilization shifts away from fatty acids and toward glucose and lactate. Capacity of the shuttles was determined in cardiac mitochondria isolated one week, one month, and three months following aortic banding or sham operation. Myocardial steady-state mRNA and protein levels of regulatory enzymes were also measured. Despite a significant increase in left ventricular mass and activation of the atrial natriuretic peptide gene, no change in malate/aspartate nor alpha -glycerophosphate shuttle capacity was found at any of the three time points studied. Reactivation of the genes encoding the regulatory inner mitochondrial membrane proteins was not found in the hypertrophied myocardium, though these genes were down regulated one week following aortic-banding. These results suggest that sufficient malate/aspartate and alpha -glycerophosphate shuttle capacity exists in cardiac mitochondria to accommodate increased shuttle flux as hypertrophied myocardium becomes more glycolytically active.

Author List

Rupert BE, Segar JL, Schutte BC, Scholz TD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Aorta
Aspartic Acid
Atrial Natriuretic Factor
Blotting, Northern
Cardiomegaly
Fatty Acids
Glucose
Glycerophosphates
Immunoblotting
Lactic Acid
Malate Dehydrogenase
Malates
Male
Mitochondria
Models, Biological
Myocardium
NAD
RNA, Messenger
Rats
Rats, Sprague-Dawley
Time Factors
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc