Rupert B E, Segar J L, Schutte B C, Scholz T D
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
J Mol Cell Cardiol. 2000 Dec;32(12):2287-97. doi: 10.1006/jmcc.2000.1257.
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.
在糖酵解活跃的新生心肌中已发现苹果酸/天冬氨酸穿梭和α-磷酸甘油穿梭（NADH穿梭）被激活。本研究的目的是确定随着底物利用从脂肪酸转向葡萄糖和乳酸，肥大心肌中的NADH穿梭及其调控基因是否被激活。在主动脉缩窄或假手术后1周、1个月和3个月分离的心脏线粒体中测定穿梭的能力。还测量了调节酶的心肌稳态mRNA和蛋白质水平。尽管左心室质量显著增加且心房利钠肽基因被激活，但在所研究的三个时间点中的任何一个时间点，均未发现苹果酸/天冬氨酸穿梭或α-磷酸甘油穿梭能力发生变化。在肥大心肌中未发现编码线粒体内膜调节蛋白的基因重新激活，尽管这些基因在主动脉缩窄后1周被下调。这些结果表明，心脏线粒体中存在足够的苹果酸/天冬氨酸穿梭和α-磷酸甘油穿梭能力，以适应肥大心肌糖酵解活性增加时穿梭通量的增加。
