Effect of mitochondrial transcription factor A (TFAM) on aging of mouse
| Project/Area Number |
17390095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KANG Dongchon Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 教授 (80214716)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2005: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | mitochondria / mitochondrial DNA / aging / TFAM / learning ability / transgenic mouse / nucleoid / oxidative stress / 活性酸素 / 電子伝達系 / 心不全 |
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| Research Abstract |
1. Mitochondrial DNA nucleoid
1.1. Identification of mitochondrial DNA nucleoid components
Mitochondrial nucleoids were purified by immunoprecipitation with anti-TFAM. The protein components of the nucleoids were identified by LC/MS/MS. Of the identified proteins, PDIP38 was first characterized.
1.2. Protective effects of hMTH1 on oxidative damage of mitochondrial DNA and cell viability
Over-expression of MTH1 in mice reduced oxidative damage of mitochondrial DNA induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as well as kinate, resulting in the improvement of cell viability. These results suggest the importance of MTH1 in preventing from oxidatative damage of mitochondrial DNA caused by oxidized free guanine nucleotide.
2. Effects of TEAM on aging of mice
TFAM-overexpressing mice were produced. The TFAM mice showed stronger resistance to cardiac infarction than wild type mice. In addition, the TFAM mice showed much better a learning ability judged by a water maze test at 24-week old than did the same aged wild type mice. These results suggest that mitochondrial DNA is involved in the aging process and that TFAM can delay the aging process by maintaining mitochondrial DNA.
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Report
(3 results)
Research Products
(40 results)
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[Journal Article] The C-terminal tail of mitochondrial transcription factor a markedly strengthens its general binding to DNA.2007
Author(s)
Ohgaki, K., Kanki, T., Fukuoh, A., Kurisaki, H., Aoki, Y., Ikeuchi, M., Kim, S.H., Hamasaki, N., Kang, D.
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Journal Title
J Biochem 141
Pages: 201-11
Description
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Protein Pept Lett 13
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Biochemistry 45
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[Journal Article] The GT to GC single nucleotide polymorphism at the beginning of an alternative exon 2C of human MTH1 gene confers an amino terminal extension that functions as a mitochondrial targeting signal.2006
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J Mol Med 84
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J Biochem 139
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Cell Death Differ 13
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[Journal Article] PDIP38 associates with proteins constituting mitochondrial DNA nucleoid.2005
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Circulation 112
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