Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasmic reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction

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 alleviate s hemodynamic dysfunction. To test this hypothesis, the effects of MET-88 o n protein content of SERCA2 were evaluated using the same rat model of hear t failure. Myocardial protein content of hexokinase, which is one of the ke y enzymes of glucose utilization, was also measured. Either MET-88 (MET-88 group) ora placebo (MI group) was administered for 20 days to rats with MI induced by coronary artery ligation. The control group underwent sham surge ry (no Ligation) and received placebo. In LV myocardial homogenates, the my ocardial SERCA2 protein content was 32 % lower (p < 0.05) in the MI group t han in the control group. However, in the MET-88 group myocardial SERCA2 co ntent was the same as in the control group. Hexokinase I protein content wa s 29 % lower (p < 0.05) in the MI group compared with the control. In contr ast, hexokinase II protein content did not differ significantly among the t hree groups. Consequently, inhibition of carnitine synthesis ameliorates de pression of SERCA2 and hexokinase I protein content which may reduce tissue damage caused by MI.