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Function analysis of the gene of an oxygen-dependent short life-scan mutant.

氧依赖性短寿命扫描突变体基因的功能分析。

基本信息

批准号：
10832008
负责人：
ISHII Naoaki
金额：
$ 2.11万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10832008/
关键词：
Oxidative stress Aging C.elegans Mitochondria Cytochrome b Electron transport Complex II life-span 酸化タンパク質突然変異

项目摘要

Much attention has been focused on the hypothesis that oxidative damage contributes to cellular and organismal aging. A mev-1 (kn1) mutant of the nematode Caenorhabditis elegans was isolated on the basis of its methyl viologen (paraquat) hypersensitivity and was also shown to be hypersensitive to hyperoxia. Unlike with wild type, its life span decreased dramatically as oxygen concentrations were increased from 1% to 60%. Strains bearing this mutation accumulated fluorescent materials and protein carbonyl groups, markers of aging, at faster rates than the wild type. We cloned mev-1 gene by transformation rescue and found that it is the previously sequenced gene (cyt-1) that encodes succinate dehydrogenase cytochrome b. The kn1 allele is a missense mutation that abolished complex II activity in the mitochondrial membrane but not succinate dehydrogenase enzyme activity per se. There are two important sets of biochemical changes in mev-1 animals that serve to explain these two phenotypes : 1) an overproduction of superoxide anion and a reciprocal reduction in glutathione content ; and 2) abnormalities in energy metabolism that likely lead to lactic acidosis. These data indicate that Cyt-1 plays an important role in the energy metabolism and protection from the oxidative stress.

很多注意力都集中在氧化损伤导致细胞和组织衰老的假说上。根据线虫对甲基紫精(百草枯)的过敏性，分离到线虫的MEV-1(Kn1)突变体，并证明其对高氧敏感。与野生型不同，当氧气浓度从1%增加到60%时，它的寿命急剧下降。携带这种突变的菌株积累荧光物质和蛋白质羰基的速度比野生型更快，这是衰老的标志。我们通过转化挽救的方法克隆了MEV-1基因，发现编码琥珀酸脱氢酶细胞色素b的是先前测序的基因(cyt-1)。Kn1等位基因是一个错义突变，使线粒体膜上的复合体II活性丧失，但本身并不影响琥珀酸脱氢酶的活性。在MEV-1动物中，有两组重要的生化变化有助于解释这两种表型：1)超氧阴离子的过度产生和谷胱甘肽含量的相对减少；2)能量代谢的异常，可能导致乳酸酸中毒。这些数据表明，Cyt-1在能量代谢和氧化应激保护中发挥着重要作用。