Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasmic reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction |
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Authors: | Katsunori Yonekura Yoko Eto Ikuo Yokoyama Akihiro Matsumoto Seiryo Sugiura Shin-ichi Momomura Tsukasa Kirimoto Yukio Hayashi Masao Omata Teruhiko Aoyagi |
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Institution: | (1) Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113-8655, E-mail: aoyagi-2im@h.u-tokyo.ac.jp, JP;(2) Taiho Pharmaceutical Co., Ltd., Tokushima, Japan, JP |
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Abstract: | It was previously reported than 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.
Received: 26 July 1999 Returned for 1. revision: 14 September 1999 1. Revision received: 14 December 1999 Returned for 2.
revision: 26 January 2000 2. Revision received: 28 February 2000 Accepted: 6 April 2000 |
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Keywords: | Carnitine inhibition – 3-(2 2 2-trimethyl-hydrazinium) propionate – sarcoplasmic reticulum Ca2+-ATPase – hexokinase – myocardial infarction |
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