Prevention of Nitric Oxide Production and Cell Deaths by Estrogen in Estrogen Receptor Expressed Rheumatoid Arthritis Fibroblasts

• Project/Area Number: 16591891
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Kagoshima University
• Principal Investigator: SUENAGA Shigeaki Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (00136889)
• Co-Investigator(Kenkyū-buntansha): TOMITA Kazuo Kagoshima University, Graduate School of Medicine and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (60347094) ; INDO Hiroko Kagoshima University, Graduate School of Medicine and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (00301391) ; MAJIMA Hideyuki Kagoshima University, Graduate School of Medicine and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (60165701)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Estrogen receptor / Estrogen / Fluorescent bioimaging / Reactive oxygen species / Nitric oxide / Apoptosis / Transfection / RNAi / エスロゲン / NO

Research Abstract

We performed a series of experiments hypothesizing that pathogenesis of RA is initially caused by generations of ROS from mitochondria and binding with NO results in lipid peroxidation and subsequent apoptosis. In addition we hypothesized that estrogen regulates mitochondrial ROS and NO productions and lipid peroxidation as a potential factors for the inhibition of apoptosis in synovial fibroblasts in RA, and these effects were dependent on the expressions of ERs.
This study indicated that (1)in RA, mitochondrial ROS and NO would be key players to cause RA pathogenesis by subsequent increase in lipid peroxidation and apoptosis ; (2)estrogen and the binding to ER plays an important role in protecting cells against cytokine-induced apoptotic cell death by controlling the generations of mitochondrial ROS and NO and lipid peroxidation in synovial fibroblasts ; (3)the differential expression of ER_results in different generations of mitochondrial ROS, NO, lipid peroxidation and subsequent apoptosis. These results support the overall hypothesis that intracellular mitochondrial ROS and NO generations and production of lipid peroxidation products subsequently accelerates apoptotic cell death and they are regulated by binding of estrogen to ER_in synovial fibroblasts.

Research Products

• [Journal Article] Intracellular oxdative stress caused by ionizing radiation. (2006)
  • Author(s): Majima HJ, Indo HP, Tomita K, Suenaga S, Motoori S, Kato H, Yen HC, Ozawa T.
  • Journal Title: Oxidative Stress, Disease and Cancer(Imperial College Press, London, UK) Pages: 61-83
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Oxidative Stress, Disease and Cancer. Intracellular oxidative stress caused by ionizing radiation (2006)
  • Author(s): Majima HJ, Indo HP, Tomita K, Suenaga S, et al.
  • Total Pages: 23
  • Publisher: Imperial College Press, London, UK.
  • Description: 「研究成果報告書概要(和文)」より