RRC ID 51835
Author Lin Y, Ohkawara B, Ito M, Misawa N, Miyamoto K, Takegami Y, Masuda A, Toyokuni S, Ohno K.
Title Molecular hydrogen suppresses activated Wnt/β-catenin signaling.
Journal Sci Rep
Abstract Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H2 reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases.
Volume 6
Pages 31986
Published 2016-8-25
DOI 10.1038/srep31986
PII srep31986
PMID 27558955
PMC PMC5001535
MeSH Adenomatous Polyposis Coli Protein / antagonists & inhibitors Adenomatous Polyposis Coli Protein / genetics Adenomatous Polyposis Coli Protein / metabolism Animals Axin Protein / metabolism Casein Kinase I / metabolism Cell Line Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism Gases / chemistry Glycogen Synthase Kinase 3 / metabolism HCT116 Cells HT29 Cells HeLa Cells Humans Hydrogen / chemistry Hydrogen / pharmacology* Leupeptins / pharmacology Lithium Chloride / pharmacology Male Microscopy, Fluorescence Osteoarthritis / metabolism Osteoarthritis / pathology Osteoarthritis / veterinary Phosphorylation / drug effects RNA Interference RNA, Small Interfering / metabolism Rats Rats, Sprague-Dawley SOX9 Transcription Factor / metabolism Water / chemistry Wnt Signaling Pathway / drug effects* Wnt3A Protein / metabolism beta Catenin / metabolism*
IF 3.998
Times Cited 9
Human and Animal Cells Hep G2(RCB1886) ATDC5(RCB0565)