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 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.
Yonekura
K
K
Department of Cardiovascular Medicine, University of Tokyo, Japan.
Eto
Y
Y
Yokoyama
I
I
Matsumoto
A
A
Sugiura
S
S
Momomura
S
S
Kirimoto
T
T
Hayashi
Y
Y
Omata
M
M
Aoyagi
T
T
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000494:pharmacology; D002331:Carnitine / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006593:Hexokinase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
C506948:Atp2a2 protein, rat; D002317:Cardiovascular Agents; D007527:Isoenzymes; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D006593:Hexokinase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002331:Carnitine