Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
FEBS Lett. 2014 Jun 27;588(14):2294-300. doi: 10.1016/j.febslet.2014.05.017. Epub 2014 May 21.
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.
解整合素金属蛋白酶 10（ADAM10）参与淀粉样前体蛋白（APP）加工过程中淀粉样β（Aβ）的产生，对 Aβ 神经毒性具有保护作用。我们探讨了金属硫蛋白-III（MT-III）如何在非淀粉样形成途径中受到调节以产生可溶性 APPα（sAPPα）。MT-ІІІ增加了 sAPPα 水平并降低了 Aβ 肽水平，但不影响 ADAM10 的表达。然而，MT-III 增加了 ADAM10 的活性。特定的 furin、前蛋白转化酶 7（PC7）和 PKCα 的抑制剂阻断了 MT-ІІІ 诱导的 sAPPα 分泌和 Aβ 肽的形成。这些结果表明，MT-ІІІ 与 furin、PC7 和 PKCα 一起增加了活性 ADAM10 的数量。
