表皮生长因子对人二倍体成纤维细胞p21^(WAF-1)基因表达的双向性影响  

The Dual Effects of Epidermal Growth Factor on Expression of p21^( WAF-1) in Human Diploid Fibroblasts during Cell Aging

作　　者：杨东丽[1] 张宗玉[1] 张凌 童坦君[1] 

机构地区：[1]北京医科大学生物化学与分子生物学系,北京100083

出　　处：《中国生物化学与分子生物学报》2000年第1期116-119,共4页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金!重点项目 ( 3 993 0 170 );国家重点基础研究发展规划资助

摘　　要：p2 1 WAF-1又称 sdi- 1 ,是细胞周期蛋白依赖性蛋白激酶 ( CDK)的抑制物基因 ,与细胞增殖调控及细胞衰老密切相关 .本研究为了解正常细胞中 p2 1 WAF-1对生长因子的反应性 ,以及其在细胞衰老时的表现 .我们以不同代龄的人胚肺二倍体成纤维细胞 ( 2 BS细胞株 )为实验对象 ,通过 Northern杂交术 ,观察表皮生长因子 ( EGF)对年轻 (低代龄 )细胞与衰老 (高代龄 )细胞 p2 1 WAF-1基因表达的影响 .结果显示 :p2 1 WAF-1在衰老 2 BS细胞中高表达 .EGF对年轻细胞 p2 1 WAF-1的表达有诱导作用 ,对衰老细胞有轻微诱导作用 ,在刺激后 3h左右达高峰 ,3～ 6h逐渐回落 ,并持续下降 .作用后 1 2h,其表达水平反而远低于作用前 .此作用在年轻细胞较为明显 .由此可见 :( 1 ) EGF对人二倍体成纤维细胞 p2 1 WAF-1的表达有双向性影响 ,先是一过性诱导 ,随后转为阻抑 ;( 2 )衰老细胞 p2 1p21 WAF 1 , also named as senescent cell derived inhibitor of DNA synthesis (sdi 1), is a cyclin dependent kinase inhibitor. It is closely related to cell growth control and cell aging. In order to understand the responsiveness of p21 WAF 1 to epidermal growth factor (EGF) in normal cells and the changes during cell aging, the expression of p21 WAF 1 was examined in human diploid fibroblasts (2BS) by Northern blotting after EGF stimulation at different population doubling (PD) levels. The results show that p21 WAF 1 was over expressed in senescent fibroblasts (55～65PD), and induced by EGF obviously in young cells (23～29PD). The peaks of the induction appeared around 3 h after the stimulation. After 3 6 h the expression declined gradually. 12 h later the expression level of p21 WAF 1 was even much lower than that before stimulation. These effects were more obvious in young cells than in old ones. It is concluded that EGF had dual effects on expression of p21 WAF 1 in 2BS, i.e.after transient induction of p21 WAF 1 , the repressing effects appeared, and the responsiveness of p21 WAF 1 to EGF in old cells was decreased.

关 键 词：p21^WAF-1 细胞衰老 基因表达 老年病 EGF 

分 类 号：Q25[生物学—细胞生物学] R592[医药卫生—老年医学]