title: Metallothionein-III increases ADAM10 activity in association with furin, PC7, and PKCα during non-amyloidogenic processing.
abstract: 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.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Park
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Suk-Gil
authors.initials: SG
authors.lastname: Song
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea. Electronic address: hgjeong@cnu.ac.kr.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D045683:Furin / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000090023:Metallothionein 3; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013381:Subtilisins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D053829:Amyloid Precursor Protein Secretases; C099101:PCSK7 protein, human; D013381:Subtilisins; C468731:FURIN protein, human; D045683:Furin; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: A-disintegrin and metalloproteinase 10; Furin; Metallothionein-III; PKCα; Proprotein convertase7; Soluble APPα