| Project/Area Number |
06044103
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Nagoya University |
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Principal Investigator |
OZAWA Takayuki Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya professor, 医学部, 教授 (80022771)
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| Co-Investigator(Kenkyū-buntansha) |
NAGLEY Phillip Department of Biochemistry, Monash University professor, 医学部, 教授
LINNANE W.An モナッシュ大学, 理学部, 教授
HAYAKAWA Mika Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya Le, 医学部, 講師 (10238090)
TANAKA Masashi Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya As, 医学部, 助教授 (60155166)
LINNANE Anthony w. Center for Molecular Biology and Medicine, Monash University professor
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| Project Period (FY) |
1994 – 1995
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| Keywords | mitochondrial DNA / electron transfer defects / mitochondrial myopathy / mutation / reactive oxygen species / deletion / aging / degenerative diseases |
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| Research Abstract |
To understand the molecular mechanisms underlying mitochondrial dysfunction in the aging process and diseases, we analyzed accumulation of oxidative damage and mutations in the mitochondrial DNA (mtDNA). 1) Hayakawa et al demonstrated an age-dependent increase in the number of deleted mtDNA was detected in skeletal muscle of human individuals of various ages. 2) Linnane et al used rat administered with AZT to demonstrate the correlation between the contractile function of skeletal muscle with mitochondrial membrane potential of heart submitochondrial particles. They also showed that coenzyme Q_<10> and several analogs can be used as potential therapeutics for the re-energization of affected tissues. 3) Vaillant and Nagley isolated mutants of human Namalwa cells, denoted rho d (mtDNA-depleted), which contain a very low mtDNA copy number. These cells may represent a useful model for human diseases in which severe depletion of cellular mtDNA levels in tissues is encountered. 4) Point mutations of mtDNA were significantly increased in a patient with encephalomyopathy MELAS.5) The amount of 8-hydroxydeoxyguanosine and detectable deleted mtDNA were increased in a patient with cardiomyopathy. 6) A total of 212 different deleted mtDNAs were detected in the heart of a 7-year-old patient who underwent heat transplantation. Thus, the accumulation of both deletions and point mutations contribute to the vicious cycle leading to tissue degeneration associated with aging and diseases.
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