https://scholars.lib.ntu.edu.tw/handle/123456789/470046
標題: | Sodium selenite inhibits γ-secretase activity through activation of ERK | 作者: | Tung Y.-T. WEN-MING HSU Wang B.-J. Wu S.-Y. Yen C.-T. Hu M.-K. Liao Y.-F. |
公開日期: | 2008 | 卷: | 440 | 期: | 1 | 起(迄)頁: | 38-43 | 來源出版物: | Neuroscience Letters | 摘要: | Previous studies have demonstrated that the ERK MAPK acts as a negative regulator of γ-secretase. Here, we demonstrate that the activation of ERK MAPK pathway by sodium selenite can inhibit endogenous γ-secretase activity. Consistently, the γ-secretase-mediated production of amyloid-β (Aβ) was dramatically attenuated by sodium selenite in a temporal manner. To substantiate the functional role of ERK MAPK in the regulation of γ-secretase, we demonstrate that cells transfected with the wild-type MEK1 and a constitutively active mutant of MEK1 also displayed a significant attenuation of γ-secretase activity. The active purified ERK1/2 can significantly reduce the γ-secretase-mediated processing of C99, possibly through inducing alterations in the phosphorylation of both nicastrin and presenilin-1. Together, our data suggest that the selenite-elicited ERK activation could effectively reduce Aβ production, supporting that selenium compounds could represent a novel class of nutrient supplements to slow down the progression of Alzheimer's disease. ? 2008 Elsevier Ireland Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-45249108210&doi=10.1016%2fj.neulet.2008.05.048&partnerID=40&md5=486b953d3fcf9aed3906b6f781c5e8b9 https://scholars.lib.ntu.edu.tw/handle/123456789/470046 |
ISSN: | 0304-3940 | DOI: | 10.1016/j.neulet.2008.05.048 | SDG/關鍵字: | amyloid beta protein[25-35]; gamma secretase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase kinase 1; mutant protein; nicastrin; presenilin 1; sodium selenite; article; controlled study; drug inhibition; enzyme activation; enzyme activity; enzyme linked immunosorbent assay; gene control; genetic transfection; human; human cell; polyacrylamide gel electrophoresis; priority journal; protein function; protein phosphorylation; Western blotting; Amyloid beta-Protein; Amyloid Precursor Protein Secretases; Cell Line, Transformed; Dose-Response Relationship, Drug; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Humans; Mutation; Peptide Fragments; Signal Transduction; Sodium Selenite; Time Factors |
顯示於: | 醫學系 |
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