Effects of apolipoprotein E (apoE) isoforms, beta-amyloid (A beta) and apoE/A beta complexes on protein kinase C-alpha (PKC-alpha) translocation and amyloid precursor protein (APP) processing in human SH-SY5Y neuroblastoma cells and fibroblasts
A. Cedazo-minguez et al., Effects of apolipoprotein E (apoE) isoforms, beta-amyloid (A beta) and apoE/A beta complexes on protein kinase C-alpha (PKC-alpha) translocation and amyloid precursor protein (APP) processing in human SH-SY5Y neuroblastoma cells and fibroblasts, NEUROCHEM I, 38(7), 2001, pp. 615-625
We investigated the effects of different apolipoprotein E (apoE) isoforms,
A beta (1-42), and apoE/A beta complexes on PKC-alpha translocation and APP
processing in human SH-SY5Y neuroblastoma cells and fibroblasts. Treatment
of cells with either 10 nM apoE3 or apoE4, 10 muM A beta (1-42), or apoE/A
beta complexes induced significant translocation of PKC-alpha in both cell
types. Effects were seen using both human recombinant apoE and apoE loaded
into P-very low density lipoprotein (P-VLDL) particles. Time course (5-24
h) studies of APP processing revealed that some conditions induced transien
t or moderate increases in the secretion of proteins detected by 22C11. In
contrast, the secretion of alpha -secretase cleaved APP was either not modi
fied or transiently decreased, as determined by immunoblotting with the ant
ibody 6E10. These results suggest that apoE, AP (1-42) and apoE/A beta comp
lexes 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. (C) 2001 El
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