HUMAN ENDOTHELIAL CELL SENESCENCE GENES

实验室已经证明，重组γ-干扰素（gIFN） 佛波醇酯（PMA）和肿瘤坏死因子（TNF）抑制人 内皮细胞增殖和r-g IFN诱导受体的损失， 内皮细胞表面HBGF-I。同样， 通过体外年龄的群体倍增（CPC>50）也导致 对HBGF-I的反应，但HBGF-I受体明显保守 内皮细胞静止与衰老诱导的静止有关。 随后，我们通过高分辨率对比2D凝胶 分析人衰老特异性多肽的表达 内皮细胞有趣的是，gIFN、PMA而不是TNF逆转了 这些衰老特异性多肽中的一些在衰老细胞中的表达 人内皮细胞群。这些数据表明， 年龄决定了他们的身份。此外，我们已经证明， 衰老细胞表达独特的可翻译的mRNA，因此希望 确定我们是否可以识别出人类内皮细胞特有的基因， 体外细胞老化。最后，我们构建了一个衰老的人， 在λ gt 10的内皮细胞cDNA文库中， 差减杂交因此，我们想进一步描述 衰老特异性多肽的二维凝胶结构 分析并独立表征推定的衰老特异性 cDNA克隆，试图为细胞的结构基础， 在体外老化过程中。

The laboratory has demonstrated that recombinant(r) gamma-interferon (gIFN) phorbol esters (PMA) and tumor necrosis factor (TNF) inhibit human endothelial cell proliferation and r-g IFN induces a loss of receptors on the endothelial cell surface for HBGF-I. Likewise, the cumulation of population doublings (CPC>50) by in vitro age also results in a loss of response to HBGF-I but with an apparent conservation of the HBGF-I receptor at endothelial cell quiescence is related to senescence induced quiescence. Subsequently, we have demonstrated by high resolution comparative 2D gel analysis the expression of senescence-specific polypeptides by human endothelial cells. Interestingly, gIFN, PMA but not TNF invert the expression of a few of these senescence-specific polypeptides in senescent populations of human endothelial cells. These data argue that in in vitro age is a determine their identity. In addition, we have demonstrated that senescent cells express unique translatable mRNAs and thus would like to determine if we can identify genes which are unique to human endothelial cell age in vitro. Lastly, we have constructed a senescence human endothelial cDNA library in lambda gt10 and have isolated 12 cDNA clones by subtraction hybridization. Thus, we would like to further characterize the structure of the senescence-specific polypeptides observed by 2D gel analysis and independently characterize the putative senescence-specific cDNA clones in an attempt to provide a structural basic for the cellular processes during in vitro aging.