Identification of the human cDNA for new survival/evasion peptide (DSEP): studies in vitro and in vivo of overexpression by neural cells.

We identified the human cDNA encoding a peptide that has been partially purified from the secretions of oxidatively stressed neural cell lines, murine adenocarcinoma cells, and group Abeta-hemolytic steptococci. We then genetically modified mouse and human neural cells to overexpress this peptide and found these modified cells to be remarkably hearty, surviving under conditions of severe oxidative stress, in xenocultures when exposed to activated macrophages, and as xenografts in the brain of rats that were not immunosuppressed. The peptide is called DSEP (dee-sep) for diffusible survival evasion peptide. Part of the survival advantage of DSEP overexpressors may be due to their attenuated response to all-trans-retinoic acid, which regulates differentiation and apoptosis of several cell types including neural and immune cells.