Alzheimer-associated presenilin-2 confers increased sensitivity to apoptosis in PC12 cells

Presenilin-2 is a gene of unknown function recently identified based upon linkage with some forms of familial Alzheimer's disease. To investigate potential effects of PS-2 on cell viability, rat pheochromocytoma (PC12) cells were stably transfected with cDNA constructs encoding either full-length human PS-2 or, for comparison, mouse Bcl-x(L). Overexpression of PS-2 conferred increased sensitivity to the apoptotic stimuli staurosporine and hydrogen peroxide. In contrast, Bcl-x(L) overexpression significantly reduced cell death induced by these stimuli. These results suggest that one function of PS-2 may involve modulation of cell viability.