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.
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.
Fukuchi
K
K
Ohman
T
T
Dang
N
N
Smith
A C
AC
Furlong
C E
CE
Martin
G M
GM
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
D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary