title: Involvement of thioredoxin reductase 1 in the regulation of redox balance and viability of rheumatoid synovial cells.
abstract: Rheumatoid arthritis (RA), a chronic and systemic disease of unknown etiology, is characterized by hyperplasia of synovial cells, which ultimately lead to the destruction of cartilage and bone. To elucidate the molecular mechanisms that lead to RA, we analyzed synovial cells established from patients with RA by oligonucleotide microarrays. Gene expression profiles clearly suggested that oxidative stress is enhanced in RA synovial cells, which was confirmed by measuring cellular levels of reactive oxygen species. One of the highly up-regulated proteins in RA synovial cells was thioredoxin reductase 1 (TRXR1), a protein that plays an important role in antioxidant defense system. Subsequent analysis demonstrated that TRXR1 suppresses hydrogen peroxide and inhibits apoptosis of RA synovial cells. Thus, our results reveal a novel pathophysiologic function of RA synovial cells as a generator of oxidative stress, and a self-defense mechanism against self-generated oxidative stress.
authors.affiliation: Department of Biomolecular Science, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Kabuyama
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitamura
authors.forename: Junko
authors.initials: J
authors.lastname: Yamaki
authors.forename: Miwako K
authors.initials: MK
authors.lastname: Homma
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Homma
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology*; D002478:Cells, Cultured; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology*; D054481:Thioredoxin Reductase 1 / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1