| Co-Investigator(Kenkyū-buntansha) |
IIJIMA Mikio Kagoshima University, Faculty of Medicine, Research Associate, 医学部, 助手 (00305111)
HORIUCHI Masahisa Kagoshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50264403)
KOBAYASHI Keiko Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70108869)
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| Research Abstract |
Carnitine is an essential co factor for β-oxidation of long-chain fatty acids. Juvenile visceral steatosis (JVS) mice have been reported as an animal model for Reye-like syndrome in 1988, suffering from fatty liver, hypoglycemia, hyperammonemia and growth retardation. Then, the mice have been established as an animal model for systemic carnitine deficiency caused by a defect of plasma membrane carnitine transport protein, Octn2. One of the most notable symptoms of the mice is cardiac hypertrophy. In the present study, we characterized the structure and function of three novel genes which differentially expressed in the ventricles of JVS mice, CDV-1, -2, and -3 (carnitine-deficiency-associated genes expressed in ventricle). CDV-1 is heart-specific gene and specifically suppressed in the hypertrophied ventricles of JVS mice, while CDV-1R is CDV-1 related gene which is expressed not only in the heart but also in the kidney and brain and not differentially expressed. CDV-1 mRNA is constructed from the 3'-half of CDV-1R and the presumed promoter sequence for CDV-1 locates in the intron 14. CDV-2 is highly expressed in the ventricles of JVS mice and was found to be a mouse homolog of pyruvate dehydrogenase kinase 4 (PDK4). The cardiac expression of CDV-3 is also augmented in the ventricles of JVS mice and suppressed by the carnitine treatment. The sequence analysis revealed that CDV-3 has a high similarity to a human predicted nuclear protein (H41) which has been reported to be up-regulated in breast cancer cells overexpressed c-erbB-2 (a kind of tyrosine kinase). These results suggest that CDV-1 and CDV-3 are directly involved in cardiac hypertrophy and CDV-2, or PDK4, is more related to carnitine deficiency. Effect of dietary lipid on the development of cardiac hypertrophy is also reported.
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