We investigated whether the type of energy metabolism directly affects cardiac gene expression. During development, the heart switches from glycolysis to fatty acid β-oxidation in vivo, as demonstrated by the developmental switching of the major isoform of myosin heavy chain (MHC) from β to α. However, the β-MHC isoform predominates in monocrotaline-induced pulmonary hypertension, a model of right ventricular hypertrophy in vivo. Cultured cardiomyocytes showed a predominance of β-MHC expression over that of α-MHC, the same pattern as in the hypertrophied heart, suggesting that the in vitro condition itself causes the energy metabolism of cardiomyocytes to be switched to glycolysis. Electrical stimulation of cultured cardiomyocytes decreased the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and hypoxia-inducible factor-1α (HIF-1α), but not that of peroxisome-proliferator-activated receptor-γ co-activator, suggesting that electrical stimulation suppresses the glycolytic system. Furthermore, a higher oxygen content (50%) decreased drastically the expression of GAPDH, HIF-1α and endothelin-1 (ET-1), and increased [3H]palmitate uptake. These findings indicate that the intrinsic energy metabolic system in cultured cardiomyocytes in vitro is predominantly glycolysis, and that the gene expression of cardiac ET-1 parallels the state of the glycolytic system. An antisense oligonucleotide against HIF-1α greatly decreased the gene expression of ET-1 and GAPDH, suggesting that cardiac ET-1 gene expression is regulated by cardiac energy metabolism through HIF-1α. In conclusion, it is suggested that the pattern of gene expression of ET-1 reflects the level of the glycolytic system in cardiomyocytes, and that enhanced glycolysis regulates the cardiac gene expression of ET-1 via HIF-1α.
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September 2002
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Conference Article|
September 01 2002
Enhancement of glycolysis in cardiomyocytes elevates endothelin-1 expression through the transcriptional factor hypoxia-inducible factor-1 α
Yoshihiko KAKINUMA;
Yoshihiko KAKINUMA
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
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Takashi MIYAUCHI;
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
Dr Takashi Miyauchi (e-mail [email protected]).
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Takahiko SUZUKI;
Takahiko SUZUKI
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
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Koichi YUKI;
Koichi YUKI
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
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Nobuyuki MURAKOSHI;
Nobuyuki MURAKOSHI
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
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Katsutoshi GOTO;
Katsutoshi GOTO
†Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
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Iwao YAMAGUCHI
Iwao YAMAGUCHI
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8575, Japan
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 210S–214S.
Citation
Yoshihiko KAKINUMA, Takashi MIYAUCHI, Takahiko SUZUKI, Koichi YUKI, Nobuyuki MURAKOSHI, Katsutoshi GOTO, Iwao YAMAGUCHI; Enhancement of glycolysis in cardiomyocytes elevates endothelin-1 expression through the transcriptional factor hypoxia-inducible factor-1 α. Clin Sci (Lond) 1 September 2002; 103 (s2002): 210S–214S. doi: https://doi.org/10.1042/CS103S210S
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