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
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.