氧化应激诱导的细胞衰老过程中细胞生长相关基因的表达

Cell Growth Associated Gene Expression in Oxidative Stress Induced Cellular Senescence

应激诱导的细胞早衰与复制性细胞衰老有相似的细胞表型,但其机制不尽相同.分析二者的衰老相关基因表达特点对了解应激因素诱导细胞衰老的机制有重要意义.本文对过氧化氢诱导的HeLa细胞早衰过程中的关键衰老相关基因及其转录后调控因子的表达做了分析.结果发现,在复制性衰老过程中明显降低的cyclin A、cyclin B1c、-fos及HuR,在温和过氧化氢诱导的细胞早衰过程中并无明显改变;在氧化应激诱导的细胞早衰过程中,p21与p16表达升高,AUF1则降低,与复制性衰老过程一致;p21 mRNA半衰期在复制性衰老过程中无明显变化,但在氧化应激诱导的细胞早衰过程中则显著延长.上述结果提示,尽管氧化应激诱导的细胞早衰与复制性衰老存在相似基因表达变化,调控机制则不尽相同.

The phenotype of stress-induced cell senescence is similar to that of replicative senescence,while the mechanisms underlying are not identical.Analyzing the expression of senescence-associated genes in these two types of cell senescence is of critical importance for better understanding the role of stress in premature senescence.In this study,we investigated the expression of key senescence-associated genes and the posttranscriptional factors involving in their regulation.The expression of cyclin A,cyclin B1,c-fos,and HuR,which was shown to be significantly reduced with replicative senescence,kept unchanged in oxidative stress induced cell aging;Increased protein levels of p21 and p16 as well as decreased AUF1 were also observed in oxidative stress induced cellular senescence,consistent with that observed in replicative senescence.The half-life of p21 mRNA,which was unchanged during replicative senescence,increased by oxidative stress.Therefore,although the expression of key senescence-associated genes in oxidative stress induced cell senescence could be similar to that of replicative senescence,the mechanisms underlying are different.