PC12 cells release stimulatory factors after transfection with beta/A4-C-terminal DNA of the Alzheimer amyloid precursor protein.
The beta/A4 region of the amyloid precursor protein (APP) accumulates in brains of victims of Alzheimer disease (AD) where it is a major component of senile plaques. We examined the pathophysiological consequences of overexpression of the beta/A4-C-terminal DNA in PC12 cells. Serum-free conditioned media (SFCM) from positive transfectants stimulated control PC12 cells to extend neurites and increase in size. Unlike the factor that affected cell size, neurite lengthening activity was significantly decreased after immunoabsorption with anti-beta/A4 monoclonal antibodies (MAb) and changes in pH. The data support the view that among the consequences of beta/A4-C-terminal DNA overexpression in PC12 cells is the release of factors that stimulate nontransfected cells to undergo morphological transformations that include differentiation to a neuronal phenotype. It is hypothesized that similar activities that may contribute to the molecular pathophysiology of the disorder may be present in the AD brain.
Majocha
R E
RE
Massachusetts General Hospital, Department of Psychiatry, Boston.
Tate
B
B
Marotta
C A
CA
D000327:Adsorption; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002448:Cell Adhesion; D002454:Cell Differentiation; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis* / Q000235:genetics; D007104:Immune Adherence Reaction; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010641:Phenotype; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D004247:DNA