Yonekura K, Eto Y, Yokoyama I, Matsumoto A, Sugiura S, Momomura S, Kirimoto T, Hayashi Y, Omata M, Aoyagi T
Department of Cardiovascular Medicine, University of Tokyo, Japan.
Basic Res Cardiol. 2000 Oct;95(5):343-8. doi: 10.1007/s003950070032.
It was previously reported that inhibition of carnitine synthesis by 3-(2,2,2-trimethyl-hydrazinium) propionate (MET-88) restores left ventricular (LV) systolic and diastolic function in rats with myocardial infarction (MI). Preservation of the calcium uptake function of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) is one of the possible mechanisms by which MET-88 alleviates hemodynamic dysfunction. To test this hypothesis, the effects of MET-88 on protein content of SERCA2 were evaluated using the same rat model of heart failure. Myocardial protein content of hexokinase, which is one of the key enzymes of glucose utilization, was also measured. Either MET-88 (MET-88 group) or a placebo (MI group) was administered for 20 days to rats with MI induced by coronary artery ligation. The control group underwent sham surgery (no ligation) and received placebo. In LV myocardial homogenates, the myocardial SERCA2 protein content was 32% lower (p<0.05) in the MI group than in the control group. However, in the MET-88 group myocardial SERCA2 content was the same as in the control group. Hexokinase I protein content was 29 % lower (p<0.05) in the MI group compared with the control. In contrast, hexokinase II protein content did not differ significantly among the three groups. Consequently, inhibition of carnitine synthesis ameliorates depression of SERCA2 and hexokinase I protein content which may reduce tissue damage caused by MI.
此前有报道称，3-(2,2,2-三甲基肼基)丙酸酯（MET-88）抑制肉碱合成可恢复心肌梗死（MI）大鼠的左心室（LV）收缩和舒张功能。肌浆网Ca2+-ATP酶（SERCA2）钙摄取功能的保留是MET-88减轻血流动力学功能障碍的可能机制之一。为验证这一假设，使用相同的心力衰竭大鼠模型评估了MET-88对SERCA2蛋白含量的影响。还测量了葡萄糖利用关键酶之一己糖激酶的心肌蛋白含量。对冠状动脉结扎诱导MI的大鼠给予MET-88（MET-88组）或安慰剂（MI组）20天。对照组进行假手术（不结扎）并接受安慰剂。在左心室心肌匀浆中，MI组的心肌SERCA2蛋白含量比对照组低32%（p<0.05）。然而，MET-88组的心肌SERCA2含量与对照组相同。MI组的己糖激酶I蛋白含量比对照组低29%（p<0.05）。相比之下，三组之间的己糖激酶II蛋白含量没有显著差异。因此，抑制肉碱合成可改善SERCA2和己糖激酶I蛋白含量的降低，这可能减少MI引起的组织损伤。
