Rheumatoid arthritis is a chronic inflammatory disease associated with joint destruction and mobility impairment. Oxidative stress generated within inflammation of the joints and is associated with autoimmune phenomena and erosion of cartilage and bone in rheumatoid synovitis. Reactive oxygen species produced from oxidative stress and caused lipid peroxidation by the depletion of unsaturated fatty acids of the cell membrane. The end-product of peroxidized ω-3 polyunsaturated fatty acids, malondialdehyde (MDA), was generated during lipid peroxidation. MDA can attack protein formed covalent-bonded adducts by reacting with lysine, histidine and arginine residues. Autoantibodies against MDA-protein adducts show high immunogenicity in diseases including rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis, peripheral artery disease, myocardial infarction, coronary artery disease, systemic vasculitis, and diabetes. In preliminary research, we found novel MDA-protein adducts and autoantibody against MDA-protein adducts in synovial fluid and serum of RA. In this study, we will investigate novel MDA-protein adducts and it's role in the pathogenesis of the rheumatoid arthritis. The study goals of year 1 included preparation and validation of MDA-modified peptide, autoantibody examination against MDA-modified peptides and MDA-protein adducts, quantitative analysis of MDA-protein adducts, and oxidant and antioxidant status associated with MDA-protein adducts in synovial fluid and serum. The study goals of year 2 are identification and quantitative analysis of MDA-modified circulating immune complexs in synovial fluid and serum, quantitative analysis of MDA-protein adducts in protein-bound circulating immune complexs and identification and quantitative analysis of MDA-protein adducts in Con A-bound synovial fluid. The study goals of year 3 are TGF-beta-induced oxidative stress of optimal concentration was investigated in NIH3T3 cell line, wild-type and mutant gene were transfect to NIH3T3 cell line, oxidant and antioxidant status associated with TGF-beta -induced NIH3T3 cell line and characteristic of MDA-modified site in MDA-protein adducts.
|Effective start/end date||8/1/14 → 7/31/15|
- Rheumatoid arthritis
- Oxidative stress
- Immune complex
- Synovial fluid