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Research on abnormal mitochondria and its change in gene expression in cellular senescence.

细胞衰老过程中线粒体异常及其基因表达变化的研究。

基本信息

批准号：
09835001
负责人：
MURANO Shunichi
金额：
$ 1.86万
依托单位：
Akita University (1998)Chiba University (1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Cultured skin fibroblasts have a limited replicative potential and it decreased by serial cultivations. This potential is called as cellular life span and its process is termed as cellular(replicative) senescence. By the way, mitochondria have charge of cellular respiratory function and indispensable in cellular maintenance. Mitochondria are always functionally exposed to oxygen and are main target of cellular damages by peroxides. Mitochondria have their own circular DNA and perform their own replication and transcription. The genes are not protected by histone proteins and do not have their own DNA repair systems. So, DNA damages are easily accumulate in mitochondrial genomes than in cellular genomes, In this research, we observed expression of mitochondrial genome by Northern analysis using a fragment of human mitochondrial DNA M1 as a probe in young and senescent cultured skin fibroblasts and fibroblasts from a patient with Werner syndrome. As a result, expressions of mitochondrial genome were decreased in senescent cells and Werner's cells than in young fibroblasts. Furthermore, we found that ratio of abnormal mitochondria being characterized by thin and long configurations, lower permiability and loss of cristae is increased in senescent cells with electron microscopy. But the morphological changes were not observed in Werner's cells which lost replicative potential by a special gene defect. Finally, these morphological changes were speculated to be induced by cumulative replications but not by replicative termination.

培养的皮肤成纤维细胞具有有限的复制潜力，并且其通过连续培养而降低。这种潜力被称为细胞寿命，其过程被称为细胞（复制）衰老。顺便说一句，线粒体负责细胞的呼吸功能，在细胞维护中不可或缺。线粒体在功能上总是暴露于氧，是过氧化物损伤细胞的主要靶点。线粒体有自己的环状DNA，并进行自己的复制和转录。这些基因不受组蛋白的保护，也没有自己的DNA修复系统。本研究以人线粒体DNA M1片段为探针，通过北方分析，观察了年轻和衰老培养的皮肤成纤维细胞和Werner综合征患者的成纤维细胞中线粒体基因组的表达。结果表明，衰老细胞和Werner细胞中线粒体基因组的表达比年轻成纤维细胞中的表达减少。电镜观察发现，衰老细胞中异常线粒体比例增加，表现为细长形、低通透性和嵴缺失。而Werner's细胞由于基因缺陷而丧失了复制能力，形态学改变不明显。最后，推测这些形态变化是由累积复制引起的，而不是由复制终止引起的。