Metabolic adaptation of the hypertrophied heart: Role of the malate/aspartate and alpha-glycerophosphate shuttles

Citation
Be. Rupert et al., Metabolic adaptation of the hypertrophied heart: Role of the malate/aspartate and alpha-glycerophosphate shuttles, J MOL CEL C, 32(12), 2000, pp. 2287-2297
Citations number
38
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
ISSN journal
00222828 → ACNP
Volume
32
Issue
12
Year of publication
2000
Pages
2287 - 2297
Database
ISI
SICI code
0022-2828(200012)32:12<2287:MAOTHH>2.0.ZU;2-Q
Abstract
Activation of the malate/aspartate and alpha -glycerophosphate shuttles (th e NADH shuttles) has been identified in glycolytically active newborn myoca rdium. The goal of this study was to determine if the NADH shuttles and the ir regulatory genes are activated in hypertrophied myocardium as substrate utilization shifts away from fatty acids and toward glucose and lactate. Ca pacity of the shuttles was determined in cardiac mitochondria isolated one week, one month, and three months following aortic banding or sham operatio n. Myocardial steady-state mRNA and protein levels of regulatory enzymes we re also measured. Despite a significant increase in left ventricular mass a nd 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 regul atory inner mitochondrial membrane proteins was not found in the hypertroph ied myocardium, though these genes were down regulated one week following a ortic-banding. These results suggest that sufficient malate/aspartate and a lpha -glycerophosphate shuttle capacity exists in cardiac mitochondria to a ccommodate increased shuttle nux as hypertrophied myocardium becomes more g rycolytically active. (C) 2000 Academic Press.