Overexpression of wild-type presenilin 2 or its familial Alzheimer's disease-associated mutant does not induce or increase susceptibility to apoptosis in different cell lines.
Programmed cell death, or apoptosis, has been implicated in Alzheimer's disease. Mutations in the presenilin (PS) genes, PS1 and PS2, are a major cause of early-onset familial Alzheimer's disease (FAD). Previous studies have suggested that the PS play a role in apoptosis. However, the mechanisms whereby presenilins affect apoptosis and the relationship of FAD-associated presenilin mutants to the apoptotic effect have not been elucidated. In the present study, in an attempt to further explore the effect of PS2 on apoptosis we examined whether overexpression of wild-type or mutant PS2 can directly induce apoptosis or increase cell susceptibility to apoptosis in various cell lines, such as N2a, CHO, and HEK 293T. Wild-type or mutant PS2 was transiently transfected into these cell lines and the viability of the transfected cells was evaluated by their morphology, DNA fragmentation and condensation, appearance of sub-G(1/0) cells, and caspase activation. We also examined the susceptibility of the PS2-transfected cells to apoptosis induced by the apoptotic inducers staurosporine and H(2)O(2). Our results showed that overexpression of either wild type or mutant PS2 in these cell lines did not directly induce apoptosis or increase the susceptibility to apoptosis induced by staurosporine or H(2)O(2). Taken together, these results suggest that overexpression of PS2 does not cause pro-apoptotic effects, at least not in the cellular systems and conditions employed in this study, and therefore it seems unlikely that apoptosis plays a prominent role in the neuropathological effects of PS2 in Alzheimer's disease.
Gamliel
A
A
Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel.
Teicher
C
C
Hartmann
T
T
Beyreuther
K
K
Stein
R
R
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000502:physiology*; D053766:Presenilin-2; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2