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Metallothionein‐III increases ADAM10 activity in association with furin, PC7, and PKCα during non‐amyloidogenic processing
Author(s) -
Park Bong Hwan,
Kim Hyung Gyun,
Jin Sun Woo,
Song Suk-Gil,
Jeong Hye Gwang
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.05.017
Subject(s) - furin , adam10 , protein kinase c , chemistry , amyloid precursor protein , metallothionein , peptide , alpha secretase , neurotoxicity , metalloproteinase , medicine , endocrinology , microbiology and biotechnology , biochemistry , disintegrin , matrix metalloproteinase , phosphorylation , alzheimer's disease , enzyme , biology , gene , toxicity , disease , organic chemistry
A‐disintegrin and metalloproteinase 10 (ADAM10) is involved in the generation of amyloid‐β (Aβ) during amyloid precursor protein (APP) processing, and has a protective effect against Aβ neurotoxicity. We explored how metallothionein‐III (MT‐III) is regulated in the non‐amyloidogenic pathway to generate soluble APPα (sAPPα). MT‐ІІІ increased sAPPα levels and reduced Aβ peptide levels, but did not affect ADAM10 expression. However, MT‐III increased the activity of ADAM10. MT‐ІІІ‐induced sAPPα secretion, and Aβ peptide formation was blocked by specific inhibitors of furin, proprotein convertase7 (PC7), and PKCα. These results demonstrate that MT‐ІІІ increases the amount of active ADAM10 in association with furin, PC7 and PKCα.