Kobayashi A, Fujisawa S
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
J Mol Cell Cardiol. 1994 Apr;26(4):499-508. doi: 10.1006/jmcc.1994.1060.
Many studies have shown that L-carnitine has a positive effect on ischemic myocardium, probably by reducing accumulation of long-chain acyl coenzyme A (CoA) esters. Previous studies have involved whole-heart extracts and have not assessed changes of CoA ester levels in mitochondria, the site of translocase inhibition. To more precisely assess L-carnitine effects, we measured long-chain acyl CoA ester levels in cytosol and in mitochondria in the ischemic canine heart. Dogs were divided into four groups: a sham-operated control group; an untreated group; and high- and low-dose L-carnitine-treated groups (30 mg/kg and 100 mg/kg). After 60 min of ischemia, the heart was excised, and the cytosolic and mitochondrial fractions were isolated. CoA esters and the activity of carnitine palmitoylcarnitine transferase (CPT) I and II were measured in both compartments. Approximately 89% of cellular free CoA. 90% of cellular acetyl CoA, 97% of cellular shot-chain acyl CoA, and 92% of cellular long-chain acyl CoA were located in the mitochondrial space under the normal condition. Under the ischemic condition, mitochondrial free CoA was significantly decreased. Conversely, mitochondrial acetyl CoA and long-chain acyl CoA were significantly increased. Treatment with L-carnitine significantly decreased acetyl CoA and long-chain acyl CoA in the ischemic mitochondrial space in a dose-dependent manner. These results support the hypothesis that L-carnitine reduces accumulation of long-chain acyl CoA within the ischemic mitochondrial space and thereby improves mitochondrial function and adenine nucleotide translocation.
许多研究表明，左旋肉碱对缺血心肌有积极作用，可能是通过减少长链酰基辅酶A（CoA）酯的积累来实现的。以往的研究涉及全心脏提取物，并未评估转位酶抑制位点——线粒体中CoA酯水平的变化。为了更精确地评估左旋肉碱的作用，我们测量了缺血犬心脏细胞质和线粒体中的长链酰基辅酶A酯水平。犬被分为四组：假手术对照组；未治疗组；高剂量和低剂量左旋肉碱治疗组（30mg/kg和100mg/kg）。缺血60分钟后，切除心脏，分离细胞质和线粒体部分。在两个部分中测量CoA酯以及肉碱棕榈酰肉碱转移酶（CPT）I和II的活性。在正常情况下，约89%的细胞游离CoA、90%的细胞乙酰CoA、97%的细胞短链酰基辅酶A和92%的细胞长链酰基辅酶A位于线粒体空间。在缺血条件下，线粒体游离CoA显著降低。相反，线粒体乙酰CoA和长链酰基辅酶A显著增加。左旋肉碱治疗以剂量依赖的方式显著降低了缺血线粒体空间中的乙酰CoA和长链酰基辅酶A。这些结果支持了以下假设：左旋肉碱减少了缺血线粒体空间内长链酰基辅酶A的积累，从而改善了线粒体功能和腺嘌呤核苷酸转运。
