SNEV overexpression extends the life span of human endothelial cells

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• 作者：Regina Voglauer ; Martina Wei-Fen Chang ; Brigitta Dampier ; Matthias Wieser ; Kristin Baumann ; Thomas Sterovsky ; Martin Schreiber ; Hermann Katinger and Johannes Grillari
• 关键词：SNEV ; Prp19 ; Endothelial cells ; Stress ; DNA damage ; Telomerase activity ; Telomere length
• 刊名：Experimental Cell Research
• 出版年：2006
• 出版时间：1 April 2006
• 年：2006
• 卷：312
• 期：6
• 页码：746-759
• 全文大小：815 K

文摘

In a recent screening for genes downregulated in replicatively senescent human umbilical vein endothelial cells (HUVECs), we have isolated the novel protein SNEV. Since then SNEV has proven as a multifaceted protein playing a role in pre-mRNA splicing, DNA repair, and the ubiquitin/proteosome system. Here, we report that SNEV mRNA decreases in various cell types during replicative senescence, and that it is increased in various immortalized cell lines, as well as in breast tumors, where SNEV transcript levels also correlate with the survival of breast cancer patients.

Since these mRNA profiles suggested a role of SNEV in the regulation of cell proliferation, the effect of its overexpression was tested. Thereby, a significant extension of the cellular life span was observed, which was not caused by altered telomerase activity or telomere dynamics but rather by enhanced stress resistance. When SNEV overexpressing cells were treated with bleomycin or bleomycin combined with BSO, inducing DNA damage as well as reactive oxygen species, a significantly lower fraction of apoptotic cells was found in comparison to vector control cells. These data suggest that high levels of SNEV might extend the cellular life span by increasing the resistance to stress or by improving the DNA repair capacity of the cells.