Yatscoff Michael A, Jaswal Jagdip S, Grant Meghan R, Greenwood Rachel, Lukat Trish, Beker Donna L, Rebeyka Ivan M, Lopaschuk Gary D
Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Pediatr Res. 2008 Dec;64(6):643-7. doi: 10.1203/PDR.0b013e318184d281.
After birth dramatic decreases in cardiac malonyl CoA levels result in the rapid maturation of fatty acid oxidation. We have previously demonstrated that the decrease in malonyl CoA is due to increased activity of malonyl CoA decarboxylase (MCD), and decreased activity of acetyl CoA carboxylase (ACC), enzymes which degrade and synthesize malonyl CoA, respectively. Decreased ACC activity corresponds to an increase in the activity of 5'-AMP activated protein kinase (AMPK), which phosphorylates and inhibits ACC. These alterations are delayed by myocardial hypertrophy. As rates of fatty acid oxidation can influence the ability of the heart to withstand an ischemic insult, we examined the expression of MCD, ACC, and AMPK in the newborn human heart. Ventricular biopsies were obtained from infants undergoing cardiac surgery. Immunoblot analysis showed a positive correlation between MCD expression and age. In contrast, a negative correlation in both ACC and AMPK expression and age was observed. All ventricular samples displayed some degree of hypertrophy, however, no differences in enzyme expression were found between moderate and severe hypertrophy. This indicates that increased expression of MCD, and the decreased expression of ACC and AMPK are important regulators of the maturation of fatty acid oxidation in the newborn human heart.
出生后，心脏丙二酰辅酶A水平急剧下降，导致脂肪酸氧化迅速成熟。我们之前已经证明，丙二酰辅酶A的减少是由于丙二酰辅酶A脱羧酶（MCD）活性增加，以及乙酰辅酶A羧化酶（ACC）活性降低，这两种酶分别负责降解和合成丙二酰辅酶A。ACC活性降低与5'-AMP激活蛋白激酶（AMPK）活性增加相对应，AMPK会使ACC磷酸化并抑制其活性。这些改变会因心肌肥大而延迟。由于脂肪酸氧化速率会影响心脏承受缺血性损伤的能力，我们检测了新生儿心脏中MCD、ACC和AMPK的表达。从接受心脏手术的婴儿身上获取心室活检组织。免疫印迹分析显示MCD表达与年龄呈正相关。相反，观察到ACC和AMPK表达与年龄呈负相关。所有心室样本均显示出一定程度的肥大，然而，在中度和重度肥大之间未发现酶表达存在差异。这表明MCD表达增加以及ACC和AMPK表达降低是新生儿心脏脂肪酸氧化成熟的重要调节因素。
