Impairment of thioredoxin reductase activity by oxidative stress in human rheumatoid synoviocytes |
| |
Authors: | Herve Lemarechal Philippe Anract Jean-Louis Beaudeux Dominique Bonnefont-Rousselot Ovanhesse G. Ekindjian |
| |
Affiliation: | 1. Biochemistry laboratory Cochin Hospital, Assistance Publique-H?pitaux de Paris, Paris, France;2. Department of Orthopedic Surgery Cochin Hospital, Assistance Publique-H?pitaux de Paris, Paris, France;3. Department of Metabolic and Clinical Biochemistry, Faculty of Pharmacy, University of Paris 5, EA 3617, Paris, France |
| |
Abstract: | The thioredoxin/thioredoxin reductase system is strongly induced in patients with rheumatoid arthritis (RA). We have investigated the impact on TR activity of doses of superoxide anion generated by the hypoxanthine (HX)/xanthine oxidase (XO) system and by hydrogen peroxide, H2O2, for various times and compared the findings with synoviocytes obtained from osteoarthritis (OA) patients. At baseline, TR activity in RA cells was significantly higher than in OA cells (2.31 ± 0.65 versus 0.74 ± 0.43 mUnit/mg protein, p < 0.01). HX/XO and H2O2 in RA cells decreased TR activity, which was found to be unchanged in OA cells. H2O2 and superoxide anion caused a time-dependent accumulation of oxidized TR and induced the formation of carbonyl groups in TR protein in RA cells rather than OA cells, and oxidized the selenocysteine of the active site. The oxidation in TR protein was irreversible in RA cells but not in OA cells. In conclusion, we report that the oxidative aggression generates modifications in the redox status of the active site of the TR and induces an alteration of the Trx/TR system, concomitant with those of the other antioxidant systems that could explain the causes of oxidative stress related to RA disease. |
| |
Keywords: | Oxidative stress thioredoxin reductase synoviocytes rheumatoid arthritis |
|
|