Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance
Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance
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DOI：
10.1152/japplphysiol.01362.2011
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发表时间：
2012-08-01
影响因子：
3.3
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Muraki, Ayako;Miyashita, Kazutoshi;Itoh, Hiroshi
[10]李晓，李晓.辅酶Q（10）逆转阿托伐他汀治疗小鼠的线粒体功能障碍，并增加运动耐力。J Appl Physiol 113：479 - 486，2012.首次发表于2012年5月31日; doi：10.1152/japplphysiol.01362.2011. -他汀类药物是广泛用于预防心血管疾病的降胆固醇药物;然而，它们与各种类型的肌病相关。他汀类药物抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，从而降低低密度脂蛋白胆固醇的生物合成，也可能减少泛醌，线粒体电子传递链的必需辅酶，其中含有类异戊二烯残基，通过HMG-CoA还原酶依赖性途径合成。因此，我们假设他汀类药物治疗可能会影响身体的表现，通过肌肉线粒体功能障碍，由于泛醌缺乏。两种他汀类药物，阿托伐他汀和普伐他汀，对泛醌含量，线粒体功能，和物理性能的影响进行了检查，使用他汀治疗的小鼠。使用培养的心肌细胞研究了与他汀类药物治疗相关的能量代谢变化。我们发现，阿托伐他汀治疗的小鼠由于泛醌缺乏和运动耐力下降而发生肌肉线粒体功能障碍，但不影响肌肉质量和力量。而普伐他汀在阿托伐他汀的10倍剂量下则无此作用。在培养的心肌细胞中，阿托伐他汀相关的线粒体活性降低导致氧利用率降低和乳酸产生增加。相反，辅酶Q（10）治疗阿托伐他汀治疗的小鼠逆转了阿托伐他汀相关的线粒体功能障碍和氧利用率下降，从而提高了运动耐力。阿托伐他汀通过泛醌缺乏引起的线粒体功能障碍降低小鼠的运动耐力。辅酶Q（10）补充泛醌可以逆转阿托伐他汀相关的线粒体功能障碍，降低运动耐量。
Muraki A, Miyashita K, Mitsuishi M, Tamaki M, Tanaka K, Itoh H. Coenzyme Q(10) reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. J Appl Physiol 113: 479-486, 2012. First published May 31, 2012; doi: 10.1152/japplphysiol.01362.2011.-Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.