Serum is required for release of Alzheimer's amyloid precursor protein in neuroblastoma cells.
The beta-amyloid peptide, the major component of the senile plaques that characterize Alzheimer's disease, is generated from a set of alternatively spliced beta-amyloid precursor proteins (APPs), which are proteolytically cleaved by the action of a set of enzymes referred to generically as secretases. The major processing pathway involves the proteolytic cleavage of APP by alpha-secretase and results in the release of soluble non-amyloidogenic full-length amino terminal fragments (sAPP), which appear to be involved in neurotrophic events. A reduced production of these neuroprotective sAPP would contribute, together with deposition of the beta-amyloid peptide, to the neurodegenerative processes that lead to the cellular death in Alzheimer's disease. In the present work, we describe a dramatic reduction of sAPP content in medium conditioned by neuronal cells grown under low-serum conditions, when compared with the levels released in the presence of 10% serum. The inhibitory effect on sAPP release appears to be quite specific since that reduction occurs without major changes in cell proliferation, expression of APP-mRNA or intracellular APP levels. Under low-serum conditions, cells showed a more differentiated morphology and no apoptotic signs were observed. Since the alpha-secretase has been described as a membrane anchored protein, our results suggest that the serum contains an essential factor(s) involved in the alpha-secretase activity.
Villa
Ana
A
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid, Spain.
Santiago
Jorge
J
García-Silva
Susana
S
Ruiz-León
Yolanda
Y
Pascual
Angel
A
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001769:Blood; D002455:Cell Division; D003470:Culture Media; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D003470:Culture Media; D020033:Protein Isoforms; D012333:RNA, Messenger