Effect of mitochondrial transcription factor A (TFAM) on aging of mouse

• Project/Area Number: 17390095
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: KANG Dongchon Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 教授 (80214716)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥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)
• 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

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.

Research Products

• [Journal Article] Mitochondrial transcription factor A (TFAM) : roles in maintenance of mtDNA and cellular functions (2007)
  • Author(s): Kang, D. et al.
  • Journal Title: Mitochondrion 7 Pages: 39-44
  • Description: 「研究成果報告書概要(和文)」より
• [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.
  • Journal Title: J Biochem 141 Pages: 201-11
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibitory effect of coenzyme Q on eukaryotic DNA polymerase gamma and DNA topoisomerase II activities on the growth of a human cancer cell line (2006)
  • Author(s): Yonezawa, Y. et al.
  • Journal Title: Cancer Sci 97 Pages: 716-723
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2006)
  • Author(s): Yamaguchi, H et al.
  • Journal Title: Cell Death Differ 13 Pages: 551-563
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The GT to GC single nucleotide polymorphism at the beginning of an alternative exon 2C of human MTll1 gene confers an amino terminal extension that functions as a mitochondrial targetine sienal. (2006)
  • Author(s): Sakai, Y. et al.
  • Journal Title: J Mol Med 84 Pages: 660-670
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The functional role of arginine 901 at the C-terminus of the human anion transporter band 3 protein (2006)
  • Author(s): Takazaki, S et al.
  • Journal Title: J Biochem 139 Pages: 903-912
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Factor XII gene (F12) -4C/C polymorphism in combination with low protein S activity is associated with deep vein thrombosis (2006)
  • Author(s): Kanaji, T. et al.
  • Journal Title: Thromb Haemost 96 Pages: 854-855
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity (2006)
  • Author(s): Kajitani, K. et al.
  • Journal Title: J Neurosci 26 Pages: 1688-1698
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Study on immunocapture-chemiluminescence assay of lipase activity in a biological sample (2006)
  • Author(s): Ichibangase, T. et al.
  • Journal Title: Luminescence 21 Pages: 62-66
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A simple secarch of TM segments in polytopic membrane protein using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (2006)
  • Author(s): Abe, Y.et al.
  • Journal Title: Protein Pept Lett 13 Pages: 761-767
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mitochondrial disease : maintenance of mitohondrial genome and molecular diagnosis (2006)
  • Author(s): Kang, D. et al.
  • Journal Title: Adv Clin Chem 42 Pages: 217-254
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of Oxidized Methionine Sites in Erythrocyte Membrane Protein using LC/ESI MS Peptide Mapping (2006)
  • Author(s): Li, C.Y.et al.
  • Journal Title: Biochemistry 45 Pages: 12117-12124
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A simple search of TM segments in polytopic membrane protein using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. (2006)
  • Author(s): Abe, Y., Hamasaki, T., Turusaki, S., Takazaki, S., Jin, X., Kang, D., Hamasaki, N.
  • Journal Title: Protein Pept Lett 13 Pages: 761-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Study on immunocapture-chemiluminescence assay of lipase activity in a biological sample. (2006)
  • Author(s): Ichibangase, T., Hamabe, C., Ohba, Y., Kishikawa, N., Nakashima, K., Kayamori, Y., Kang, D., Hamasaki, N., Kuroda, N.
  • Journal Title: Luminescence 21 Pages: 62-66
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity. (2006)
  • Author(s): Kajitani, K., Yamaguchi, H., Dan, Y., Furuichi, M., Kang, D., Nakabeppu, Y.
  • Journal Title: J Neurosci 26 Pages: 1688-98
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Factor XII gene (F12)-4C/C polymorphism in combination with low protein S activity is associated with deep vein thrombosis. (2006)
  • Author(s): Kanaji, T., Watanabe, K., Hattori, S., Urata, M., Iida, H., Kinoshita, S., Kayamori, Y., Kang, D., Hamasaki, N.
  • Journal Title: Thromb Haemost 96 Pages: 854-5
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of Oxidized Methionine Sites in Erythrocyte Membrane Protein using LC/ESI MS Peptide Mapping. (2006)
  • Author(s): Li, C.Y., Takazaki, S., Jin, X.R., Kang, D., Abe, Y., Hamasaki, N.
  • Journal Title: Biochemistry 45 Pages: 12117-12124
  • Description: 「研究成果報告書概要(欧文)」より
• [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)
  • Author(s): Sakai, Y., Oda, H., Yoshimura, D., Furuichi, M., Kang, D., Iwai, S., Hara, T., Nakabeppu, Y.
  • Journal Title: J Mol Med 84 Pages: 660-670
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The functional role of arginine 901 at the C-terminus of the human anion transporter band 3 protein. (2006)
  • Author(s): Takazaki, S., Abe, Y., Kang, D., Li, C., Jin, X., Ueda, T., Hamasaki, N.
  • Journal Title: J Biochem 139 Pages: 903-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. (2006)
  • Author(s): Yamaguchi, H., Kajitani, K., Dan, Y., Furuichi, M., Ohno, M., Sakumi, K., Kang, D., Nakabeppu, Y.
  • Journal Title: Cell Death Differ 13 Pages: 551-63
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibitory effect of coenzyme Q on eukaryotic DNA polymerase gamma and DNA topoisomerase II activities on the growth of a human cancer cell line. (2006)
  • Author(s): Yonezawa, Y., Kuriyama, I., Fukuoh, A., Muta, T., Kang, D., Takemura, M., Kato, I., Yoshida, H., Mizushina, Y.
  • Journal Title: Cancer Sci 97 Pages: 716-23
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells. (2006)
  • Author(s): Goto, Y., Hayashi, R., Kang, D., Yoshida, K.
  • Journal Title: J Cell Physiol 209 Pages: 923-34
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (2006)
  • Author(s): Yamaguchi, H et al.
  • Journal Title: Cell Death Differ 13 Pages: 551-563
• [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)
  • Author(s): Sakai, Y. et al.
  • Journal Title: J Mol Med 84 Pages: 660-670
• [Journal Article] Study on immunocapture-chemiluminescence assay of lipase activity in a biological sample (2006)
  • Author(s): Ichibangase, T. et al.
  • Journal Title: Liminescence 21 Pages: 62-66
• [Journal Article] A simple search of TM segments in polytopic membrane protein using matrix-assisted desorption ionization time-of-flight mass spectrometry (2006)
  • Author(s): Abe, Y.et al.
  • Journal Title: Protein Pept Lett 13 Pages: 761-767
• [Journal Article] Mitochondrial disease : maintenance of mitohondrial genome and molecular diagnosis (2006)
  • Author(s): Kang.D.et al.
  • Journal Title: Adv Clin Chem 42 Pages: 217-254
• [Journal Article] Synergistic enhancement of TRAIL- and tumor necrosis factor alpha-induced cell death by a phenoxazine derivative (2005)
  • Author(s): Hara, K.
  • Journal Title: Mol Cancer Ther 4 Pages: 1121-1127
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction (2005)
  • Author(s): Ikeuchi, M.
  • Journal Title: Circulation 112 Pages: 683-690
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protein S and protein C gene mutations in Japanese deep vein thrombosis patients (2005)
  • Author(s): Kinoshita, S.
  • Journal Title: Clin Biochem 38 Pages: 908-915
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PDIP38 associates with proteins constituting mitochondrial DNA nucleoid (2005)
  • Author(s): Cheng, X.
  • Journal Title: J Biochem 138 Pages: 673-678
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Study on immunocapture-chemiluminescence assay of lipase activity in a biological sample (2005)
  • Author(s): Ichibangase, T.
  • Journal Title: Luminescence 21 Pages: 62-66
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alterations of Mitochondrial DNA in Common Diseases and Disease States : Aging, Neurodegeneration, Heart Failure, Diabetes and Cancer (2005)
  • Author(s): Kang, D.
  • Journal Title: Curr. Med. Chem. 12 Pages: 429-441
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PDIP38 associates with proteins constituting mitochondrial DNA nucleoid. (2005)
  • Author(s): Cheng, X., Kanki, T., Fukuoh, A., Ohgaki, K., Takeya, R., Aoki, Y., Hamasaki, N., Kang, D.
  • Journal Title: J Biochem 138 Pages: 673-678
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Synergistic enhancement of TRAIL- and tumor necrosis factor alpha-induced cell death by a phenoxazine derivative. (2005)
  • Author(s): Hara, K., Okamoto, M., Aki, T., Yagita, H., Tanaka, H., Mizukami, Y., Nakamura, H., Tomoda, A., Hamasaki, N., Kang, D.
  • Journal Title: Mol Cancer Ther 4 Pages: 1121-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction. (2005)
  • Author(s): Ikeuchi, M., Matsusaka, H., Kang, D., Matsushima, S., Ide, T., Kubota, T., Fujiwara, T., Hamasaki, N., Takeshita, A., Sunagawa, K., Tsutsui, H.
  • Journal Title: Circulation 112 Pages: 683-90
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protein S and protein C gene mutations in Japanese deep vein thrombosis patients. (2005)
  • Author(s): Kinoshita, S., Iida, H., Inoue, S., Watanabe, K., Kurihara, M., Wada, Y., Tsuda, H., Kang, D., Hamasaki, N.
  • Journal Title: Clin Biochem 38 Pages: 908-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Synergistic enhancement of TRAIL-and tumor necrosis factor alpha-induced cell death by a phenoxazine derivative (2005)
  • Author(s): Hara, K.
  • Journal Title: Mol Cancer Ther 4 Pages: 1121-1127
• [Journal Article] PDIP38 associates with proteins constituting mitoehondrial DNA nucleoid (2005)
  • Author(s): Cheng, X.
  • Journal Title: J Biochem 138 Pages: 673-678
• [Journal Article] Alterations of Mitochondrial DNA in Common Diseases and Disease States : Aging, Neurodegeneration, Heart Failure, Diabetes and Cancer (2005)
  • Author(s): Kang, D.
  • Journal Title: Curr.Med.Chem. 12 Pages: 429-441