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Blockade of PKC epsilon activation attenuates phorbol ester-induced increase of alpha-secretase-derived secreted form of amyloid precursor protein.

Yeon, SW; Jung, MW; Ha, M; Kim, SU; Huh, K; Savage, MJ; Masliah, E; Mook-Jung, I
Biochemical and biophysical research communications, 280(3):782-787, 2001
Journal Title
Biochemical and biophysical research communications

The role of PKC epsilon in amyloid precursor protein (APP) processing was investigated using APP-overexpressing B103 cells. As reported previously, a PKC activator, phorbol-12,13-dibutyrate (PDBu), enhanced secretion of APP alpha, and this effect was blocked by a PKC inhibitor, GF109203X in this system. Selective inhibition of PKC epsilon by overexpressing the PKC epsilon V1 region, which binds specifically to the receptor for activated C-kinase (RACK), blocked PDBu-induced enhancement of APP alpha secretion as well as PDBu-induced decrease in beta-secretase-derived APP C-terminal fragment production. On the other hand, the level of PKC epsilon, but not that of PKC alpha or PKC gamma, was substantially lower in the brains of Alzheimer's disease patients compared to age-matched controls. These results add to a growing body of evidence that PKC epsilon plays an important role in modulating APP processing, and suggest that reduced PKC epsilon activity may contribute to the development of Alzheimer's disease.
MeSH terms
Alzheimer Disease/etiologyAlzheimer Disease/metabolismAmyloid Precursor Protein SecretasesAmyloid beta-Protein Precursor/secretion*AnimalsAspartic Acid EndopeptidasesBase SequenceBrain/enzymologyCase-Control StudiesCell LineDNA Primers/geneticsEndopeptidases/metabolism*Enzyme Activation/drug effectsHumansIsoenzymes/geneticsIsoenzymes/metabolism*Phorbol 12,13-Dibutyrate/pharmacologyProtein Kinase C/geneticsProtein Kinase C/metabolism*Protein Kinase C-epsilonProtein Processing, Post-TranslationalRatsTransfection
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
정, 민환하, 만준김, 승업허, 균묵, 인희
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