Human amyloid-beta causes changes in the levels of endothelial protein kinase C and its alpha isoform in vitro.
Amyloid-beta (A(beta)) deposits and neurofibrillary pathology are characteristic features of Alzheimer's disease (AD). The association of A(beta) with cerebral vessels is an intriguing feature of AD. While there is considerable evidence of altered activities of the major isoforms of protein kinase C (PKC) in the vasculature and neurons of AD brains, little is known about the relationship between the Abeta toxicity and the altered PKC levels in cerebral endothelial cells. In this study, cultured brain endothelial cells exposed to A(beta)1-40 revealed a translocation of PKC from the membrane fraction to the cytosol. The content of the isoform PKC(alpha), involved in the regulation of amyloid precursor protein (APP) secretion, was decreased in the membrane-bound fraction of rat endothelial cells and increased in the cytosol after A(beta)1-40 treatment. These data suggest that the accumulation of A(beta) peptide in the cerebral vasculature may play a significant role in the down-regulation of PKC seen in the AD cerebral vasculature.
Pakaski
Magdolna
M
Department of Psychiatry, Alzheimer's Disease Research Centre, University of Szeged, Somogyi 4, H-6720 Szeged, Hungary. pakaski@comser.szote-u.szeged.hu
Balaspiri
Lajos
L
Checler
Frederic
F
Kasa
Peter
P
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051381:Rats
D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha