SNEV overexpression extends the life span of human endothelial cells.
In a recent screening for genes down regulated 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.
Voglauer
Regina
R
Institute of Applied Microbiology, Department of Biotechnology, University of Natural Resources and Applied Life Sciences Muthgasse 18, A-1190 Vienna, Austria.
Chang
Martina Wei-Fen
MW
Dampier
Brigitta
B
Wieser
Matthias
M
Baumann
Kristin
K
Sterovsky
Thomas
T
Schreiber
Martin
M
Katinger
Hermann
H
Grillari
Johannes
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D045643:DNA Repair Enzymes; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human