title: Overexpressions of cDNAs for beta-amyloid precursor proteins 695, 751, and 770 enhance the secretion of beta-amyloid precursor protein derivatives and the survival of P19-derived neurons.
abstract: P19 is a C3H mouse-derived line of multipotent embryonic carcinoma cells that differentiate into neural cells. P19 cell clones overexpressing the three major forms of beta-amyloid precursor protein from their cDNA constructs were established. Unlike a previous study in which P19-derived neurons had a limited alpha-secretase activity, all of these clones produced significant amounts of secreted beta-amyloid precursor protein. When treated with retinoic acid, these transformed lines differentiated into neurons and survived better than did nontransformed parental P19 cells. Furthermore, P19-derived neurons survived better in medium conditioned by the transformed P19 line, and survival was reduced by immunoabsorption with an antibody to beta-amyloid precursor protein. These results suggest neurotrophic effects of secreted beta-amyloid precursor protein and contrast with a previous report in which overexpression of a full-length cDNA for beta-amyloid precursor protein led to degeneration of P19-derived neurons. Western blot analysis suggested that this difference might result from different levels of expression of putative neurotoxic C-terminal fragments of beta-amyloid precursor protein; moreover, P19-derived neurons differ from P19 stem cells in the processing of these C-terminal fragments.
authors.forename: K
authors.initials: K
authors.lastname: Fukuchi
authors.forename: T
authors.initials: T
authors.lastname: Ohman
authors.forename: N
authors.initials: N
authors.lastname: Dang
authors.forename: A C
authors.initials: AC
authors.lastname: Smith
authors.forename: C E
authors.initials: CE
authors.lastname: Furlong
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000031:analogs & derivatives* / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D018076:DNA, Complementary / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009474:Neurons / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary