Ishii Naoaki, Ishii Takamasa, Hartman Philip S
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
Exp Gerontol. 2006 Oct;41(10):952-6. doi: 10.1016/j.exger.2006.06.037. Epub 2006 Sep 7.
Much attention has been focused on the hypothesis that oxidative damage contributes to cellular and organismal aging. A mev-1 mutation in the cytochrome b large subunit (SDHC) of complex II results in superoxide anion (O(2)(-)) overproduction and therefore leads to apoptosis and precocious aging in the nematode Caenorhabditis elegans. To extend these data, a transgenic mouse cell line was constructed with a homologous mutation to mev-1. Many of the mutant nematode phenotypes (e.g., increased superoxide anion production, apoptosis) were recapitulated in the mouse. In addition, a significant fraction of the cells that survived apoptosis were transformed. These data support the notion that oxidative stress from mitochondria play an important role of both apoptosis, which leads to precocious aging, and cancer.
许多注意力都集中在氧化损伤导致细胞和机体衰老的假说上。复合物II细胞色素b大亚基（SDHC）中的mev-1突变会导致超氧阴离子（O(2)(-)）过量产生，进而导致线虫秀丽隐杆线虫凋亡和早衰。为了扩展这些数据，构建了一个与mev-1具有同源突变的转基因小鼠细胞系。小鼠重现了许多突变线虫的表型（例如，超氧阴离子产生增加、凋亡）。此外，很大一部分在凋亡中存活下来的细胞发生了转化。这些数据支持了这样一种观点，即线粒体产生的氧化应激在导致早衰的凋亡和癌症中都起着重要作用。
