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

线粒体转录因子A（TFAM）对小鼠衰老的影响

• 批准号: 17390095
• 负责人: KANG Dongchon
• 金额: $ 9.41万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390095/
• 关键词: mitochondria; mitochondrial DNA; aging; TFAM; learning ability; transgenic mouse; nucleoid; oxidative stress; 活性酸素; 電子伝達系; 心不全

1. Mitochondrial DNA nucleoid1.1. Identification of mitochondrial DNA nucleoid componentsMitochondrial 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 viabilityOver-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 miceTFAM-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.

1.线粒体DNA核蛋白1.1。线粒体DNA类核组分的鉴定用抗TFAM抗体免疫沉淀法纯化线粒体类核。通过LC/MS/MS鉴定了类核的蛋白组分。在鉴定的蛋白中，首先表征了PDIP 38。hMTH 1对线粒体DNA氧化损伤和细胞活力的保护作用过量表达MTH 1可减轻1-甲基-4-苯基-1，2，3，6-四氢吡啶和kinate对线粒体DNA的氧化损伤，提高细胞活力。这些结果提示MTH 1在防止氧化游离鸟嘌呤核苷酸引起的线粒体DNA氧化损伤中的重要作用.研究了TEAM对小鼠衰老的影响。TFAM小鼠比野生型小鼠表现出更强的抗心肌梗死能力。此外，TFAM小鼠在24周龄时通过水迷宫测试判断的学习能力比同龄野生型小鼠好得多。这些结果表明，线粒体DNA参与衰老过程，TFAM可以通过维持线粒体DNA来延缓衰老过程。

项目成果

Synergistic enhancement of TRAIL- and tumor necrosis factor alpha-induced cell death by a phenoxazine derivative.

吩恶嗪衍生物协同增强 TRAIL 和肿瘤坏死因子 α 诱导的细胞死亡。

• 发表时间: 2005
• 期刊: Mol Cancer Ther 4
• 作者: Hara;K.;Okamoto;M.;Aki;T.;Yagita;H.;Tanaka;H.;Mizukami;Y.;Nakamura;H.;Tomoda;A.;Hamasaki;N.;Kang;D.
• 通讯作者: D.

PDIP38 associates with proteins constituting mitochondrial DNA nucleoid.

PDIP38 与构成线粒体 DNA 核仁的蛋白质相关。

• 发表时间: 2005
• 期刊: J Biochem 138
• 作者: Cheng;X.;Kanki;T.;Fukuoh;A.;Ohgaki;K.;Takeya;R.;Aoki;Y.;Hamasaki;N.;Kang;D.
• 通讯作者: D.

A simple search of TM segments in polytopic membrane protein using matrix-assisted desorption ionization time-of-flight mass spectrometry

使用基质辅助解吸电离飞行时间质谱法简单搜索多面体膜蛋白中的 TM 片段

• 发表时间: 2006
• 期刊: Protein Pept Lett 13
• 作者: Abe;Y.et al.
• 通讯作者: Y.et al.

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.

人 MTH1 基因替代外显子 2C 起始处的 GT 至 GC 单核苷酸多态性赋予氨基末端延伸，起到线粒体靶向信号的作用。

• 发表时间: 2006
• 期刊: Journal of Molecular Medicine (in press)
• 作者: Y.Nakabeppu;et al.;Y.Sakai et al.
• 通讯作者: Y.Sakai et al.

Synergistic enhancement of TRAIL- and tumor necrosis factor alpha-induced cell death by a phenoxazine derivative

吩恶嗪衍生物协同增强 TRAIL 和肿瘤坏死因子 α 诱导的细胞死亡

• 发表时间: 2005
• 期刊: Mol Cancer Ther 4
• 作者: Hara;K.
• 通讯作者: K.