Protein kinase C epsilon suppresses Abeta production and promotes activation of alpha-secretase.
Biochem Biophys Res Commun
; 285(4): 997-1006, 2001 Jul 27.
Article
in En
| MEDLINE
| ID: mdl-11467851
ABSTRACT
Deposition of plaques containing Abeta is considered important in the pathogenesis of Alzheimer's disease. Phorbol esters that activate protein kinase C (PKC) promote alpha-secretase-mediated processing of the beta amyloid precursor protein (APP), which generally reduces formation of Abeta. To determine which PKC isozymes mediate this process, we studied CHO cells that express human APP751. Phorbol 12-myristate, 13-acetate (PMA)-stimulated APP secretion, which was reduced by a general PKC inhibitor bisindoylmaleimide I, but not by Gö 6976, which inhibits PKCalpha, beta, gamma, and mu. Since PKCdelta and epsilon were the only other PMA-sensitive isozymes present, we studied cells that express selective peptide inhibitors of these isozymes. Expression of the PKCepsilon inhibitor inhibited PMA-induced APPs secretion and suppression of Abeta production. In contrast, the PKCdelta inhibitor had no effect. These results provide evidence that PKCepsilon decreases Abeta production by promoting alpha-secretase mediated cleavage of APP.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endopeptidases
/
Protein Kinase C
/
Amyloid beta-Peptides
/
Amyloid beta-Protein Precursor
/
Isoenzymes
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2001
Document type:
Article
Affiliation country:
Estados Unidos