Atlante Anna, Seccia Teresa M, De Bari Lidia, Marra Ersilia, Passarella Salvatore
Istituto di Biomembrane e Bioenergetica, CNR, Bari, Italy.
Int J Mol Med. 2006 Jul;18(1):177-86.
A substantial increase in NADH production, arising from accelerated glycolysis, occurs in cardiac hypertrophy and this raises the question of how the NADH is oxidised. We have addressed this problem by reconstructing appropriate mitochondrial shuttles in vitro, using mitochondria from the left ventricles of both normotensive and spontaneously hypertensive rats at 5 and 24 weeks of age as model systems for left ventricle hypertrophy and hypertrophy/hypertension respectively. We found that most NADH oxidation occurs via a novel malate/oxaloacetate shuttle, the activity of which increases with time and with the progression of hypertrophy and development of hypertension as judged by statistical ANOVA analysis. In contrast, alpha-glycerol-phosphate and the malate/aspartate shuttles were shown to make only a minor contribution to NADH oxidation in a manner essentially independent of age and progression of hypertrophy/hypertension. The rate of malate transport in exchange with oxaloacetate proved to limit the rate of NADH oxidation via this malate/oxaloacetate shuttle.
在心脏肥大过程中，由于糖酵解加速，NADH生成显著增加，这就引发了NADH如何被氧化的问题。我们通过体外重建合适的线粒体穿梭系统来解决这个问题，使用5周龄和24周龄正常血压大鼠及自发性高血压大鼠左心室的线粒体，分别作为左心室肥大和肥大/高血压的模型系统。我们发现，大多数NADH氧化通过一种新的苹果酸/草酰乙酸穿梭系统进行，通过统计方差分析判断，其活性随时间以及肥大进展和高血压发展而增加。相比之下，α-甘油磷酸穿梭系统和苹果酸/天冬氨酸穿梭系统对NADH氧化的贡献很小，且其方式基本独立于年龄以及肥大/高血压的进展。事实证明，苹果酸与草酰乙酸交换的转运速率限制了通过该苹果酸/草酰乙酸穿梭系统的NADH氧化速率。
