Caenorhabditis elegans as a screening tool for the endothelial cell-derived putative aging-related proteins detected by proteomic analysis
Caenorhabditis elegans as a screening tool for the endothelial cell-derived putative aging-related proteins detected by proteomic analysis
复制标题
DOI：
10.1002/pmic.200500395
复制
发表时间：
2006-06-01
期刊：
影响因子：
3.4
通讯作者：
Chung, Kee Yang
中科院分区：
文献类型：
--
作者：
Ha, Moon Kyung;Cho, Jeong Soo;Chung, Kee Yang
随着细胞衰老的进展，内皮细胞经历进行性病理生理学修饰。在体外，内皮细胞衰老伴随着增殖的失败以及基因和蛋白质表达的扰动。此外，这种细胞衰老的文化已被提出，以反映在生物体内发生的过程和自由基理论被认为是最合理的解释这个过程。我们利用二维凝胶分析筛选了参与细胞衰老和活性氧诱导条件的蛋白质，发现泛素羧基末端水解酶L1、过氧氧化还原蛋白2、过氧氧化还原蛋白4、脂肪酸结合蛋白（FABPs）和5 '-AMP活化蛋白激酶β 1亚基是衰老相关蛋白的候选者。为了评价这些蛋白在体内的功能，秀丽隐杆线虫（C. elegans）敲减系统。脂岩藻素的衰老特异性表达和敲低的C.观察线虫以评估结果。有趣的是，与野生型相比，基因的抑制导致寿命缩短，随着年龄的增加，脂岩藻素的积累更早。这些结果表明，上述基因可能与细胞衰老过程有关，在决定长寿的C。线虫和基因失活使动物对氧化应激敏感。
Endothelial cells go through progressive pathophysiologic modification as cellular senescence progresses. In vitro, endothelial cell senescence is accompanied by failure of proliferation and by perturbations in gene and protein expressions. Moreover, this cellular senescence in culture has been proposed to reflect processes that occur in the organism in vivo and free radical theory is accepted to be the most plausible explanation for this process. We have screened proteins involved in both cellular senescence and reactive oxygen species induced condition using 2-D gel analysis and found that ubiquitin carboxyl terminal hydrolase L1, peroxyredoxin 2, peroxyredoxin 4, fatty acid binding proteins (FABPs), and 5'-AMP-activated protein kinase beta-1 subunit were candidate aging-related proteins. To evaluate in vivo function of these proteins, Caenorhabditis elegans (C. elegans) knock-down system using RNA interference was applied. Aging-specific expression of lipofucsin and the lifespan of knocked-down C. elegans were observed to assess the outcome. Interestingly, the inhibition of the genes led to short lifespan and earlier accumulation of lipofucsin with increasing age when compared with the wild type. These results suggest that the above genes may be related to cellular senescence process in determining the longevity in C. elegans and that gene inactivation renders animals susceptible to oxidative stress.