SHIMOMURA Yoshiharu NAGOYA INST.OF TECHNOL.PROFESSOR, 工学部, 教授 (30162738)
谷口 健次 名古屋大学, 医学部, 医員
NAKAO Akimasa NAGOYA UNIV.SCHOOL OF MED.ASSOCIATE PROFESSOR, 医学部, 助教授 (70167542)
TAKAGI Hiroshi NAGOYA UNIV.SCHOOL OF MED.PROFESSOR, 医学部, 教授 (70154755)
KUROKAWA Tsuyoahi NAGOYA UNIV.SCHOOL OF MED.ASSISTANT PROFESSOR, 医学部, 助手 (50291406)
|Budget Amount *help
¥7,400,000 (Direct Cost : ¥7,400,000)
Fiscal Year 1997 : ¥3,700,000 (Direct Cost : ¥3,700,000)
Fiscal Year 1996 : ¥3,700,000 (Direct Cost : ¥3,700,000)
In study 1, in order to evaluate the effects of chronic liver diseases on mitochondrial DNA (mtDNA) transcription and replication, nuclear respiratory factor-1 (NRF-1) mRNA,mitochondrial transcription factor A (mtTFA) mRNA,a RNA component of ribonuclease (RNase) for mitochondrial RNA processing (MRP), mitochondrial cytochrome b mRNA,and mtDNA were reasured in normal, chronically viral-hepatitic and cirrhotic human livers. The expression levels of the regulatory factors for mitochondrial gene (NRF-1 and mtTFA) and cytochrome b mRNA were significantly increased by chronic hepatitis (160,280, and 175%, respectively) compared with those in normal livers, but were not different between cirrhotic and normal livers. On the other hand, concentrations of mtDNA and RNA component of RNAase MRP were not different among normal, chronically hepatitic, and cirrhotic livers. These results suggest that either persistent hepatitis viral infection or repeated cell necrosis and regeneration in chronically hepatitic livers may be associated with enhancement of the expression of the mitochondrial gene, and that mitochondrial transcription and replication in liver may not be damaged by chronic liver diseases.
In study 2, we measured the populations of mutated mitochondrial DNAs with the 7,436 bp or the 4,977 bp deletion from apparent normal human liver and human livers with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The amount of the mutated mtDNA was at the same level between normal and chronic hepatitic livers but was significantly lower in human livers with cirrhosis and hepatocellular carcinoma, especially the latter, than in normal human liver, suggesting that the mutated mitochondrial DNAs may be decreased with the progress of liver disease from chronic hepatitis to cirrhosis and hepatocellular carcinoma, being a phenomenon reverse to the aging process.