期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 285, 期 4, 页码 997-1006出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2001.5273
关键词
alpha secretase; protein kinase C epsilon; phorbol ester; A beta peptide; Alzheimer's disease
资金
- NIAAA NIH HHS [AA10036] Funding Source: Medline
- NIA NIH HHS [AG05834, AG12376] Funding Source: Medline
Deposition of plaques containing A beta 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 A beta. To determine which PKC isozymes mediate this process, we studied CHO cells that express human APP(751). Phorbol 12-myristate, 13-acetate (PMA)-stimulated APP secretion, which was reduced by a general PKC inhibitor bisindoylmaleimide I, but not by Go 6976, which inhibits PKC alpha, beta, gamma, and mu. Since PKC delta and epsilon were the only other PMA-sensitive isozymes present, we studied cells that express selective peptide inhibitors of these isozymes. Expression of the PKC epsilon inhibitor inhibited PMA-induced APPs secretion and suppression of A beta production. In contrast, the PKC delta inhibitor had no effect. These results provide evidence that PKC epsilon decreases A beta production by promoting alpha -secretase mediated cleavage of APP. (C) 2001 Academic Press.
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