Effects of apolipoprotein E (apoE) isoforms, beta-amyloid (A-beta) and apoE/A-beta complexes on Protein Kinase C-alfa (PKC-alfa) translocation and amyloid precursor protein (APP) processing in human SH-SY5Y neuroblastoma cells and fibroblasts
Angel Cedazo-Minguez, Birgitta Wiehager, Bengt Winblad, Manfred Hüttinger, Richard F. Cowburn
Bok Engelsk 2002 ╡ngel Cedazo-Mínguez
| Utgitt | 2002
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| Omfang | 11 s.
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| Opplysninger | Abstract: We investigated the effects of different apolipoprotein E (apoE) isoforms, A-beta (1-42), and apoE/A-beta complexes on PKC-alfa translocation and APP processing in human SH-SY5Y neuroblastoma cells and fibroblasts. Treatment of cells with either 10 nM apoE3 or apoE4, 10 my-M A-beta (1-42), or apoE/A-beta complexes induced significant translocation of PKC-alfa: in both cell types. Effects were seen using both human recombinant apoE and apoE loaded into beta-very low density lipoprotein (beta-VLDL) particles. Time course (5-24 h) studies of APP processing revealed that some conditions induced transient or moderate increases in the secretion of proteins deteeted by 22Cll. In contrast, the secretion of alfa-secretase cleaved APP was either not modified or transiently decreased, as determined by immunoblotting with the antibody 6EIO. These results suggest that apoE, A-beta (1-42) and apoE/A-beta complexes can modulate PKC activity but do not have major consequences for APP processing. These effects could contribute to the reported PKC alterations seen in AD. However, it is unlikely that the contribution of different apoE isoforms to AD pathology occurs via effects on APP processing.
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