Protein kinase C ε suppresses Aβ production and promotes activation of α-secretase

被引:71
作者
Zhu, GF
Wang, D
Lin, YH
McMahon, T
Koo, EH
Messing, RO
机构
[1] UCSF, Ernest Gallo Clin & Res Ctr, Dept Neurol, Emeryville, CA 94608 USA
[2] UCSF, Grad Program Neurosci, Emeryville, CA 94608 USA
[3] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA
关键词
alpha secretase; protein kinase C epsilon; phorbol ester; A beta peptide; Alzheimer's disease;
D O I
10.1006/bbrc.2001.5273
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:997 / 1006
页数:10
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