Hypoxia induces nitric oxide synthase in rheumatoid synoviocytes: consequences on NADPH oxidase regulation

被引：8

作者：

Chenevier-Gobeaux, Camille ^{[1
]}

Simonneau, Catherine ^{[1
]}

Lemarechal, Herve ^{[1
]}

Bonnefont-Rousselot, Dominique ^{[2
]}

Poiraudeau, Serge ^{[3
]}

Rannou, Francois ^{[3
,4
]}

Anract, Philippe ^{[5
]}

Borderie, Didier ^{[1
,2
]}

机构：

[1] Univ Paris 05, Grp Hosp Cochin Broca Hotel Dieu, AP HP, Biochim Lab, F-75679 Paris 14, France

[2] Univ Paris 05, EA4466, Fac Pharm, Paris 06, France

[3] Univ Paris 05, Grp Hosp Cochin Broca Hotel Dieu, AP HP, Serv Reeducat & Readaptat Fonct Appareil Locomote, F-75679 Paris 14, France

[4] Univ Paris 05, INSERM, UMR 747, F-75679 Paris 14, France

[5] Univ Paris 05, Grp Hosp Cochin Broca Hotel Dieu, AP HP, Serv Orthopedie, F-75679 Paris 14, France

来源：

FREE RADICAL RESEARCH | 2012年 / 46卷 / 05期

关键词：

hypoxia; NADPH oxidase; NO synthase; rheumatoid synoviocytes; FIBROBLAST-LIKE SYNOVIOCYTES; NECROSIS-FACTOR-ALPHA; SYNOVIAL-CELLS; SUPEROXIDE-PRODUCTION; RESPIRATORY BURST; ENDOTHELIAL-CELLS; S-NITROSYLATION; FREE-RADICALS; ARTHRITIS; EXPRESSION;

D O I：

10.3109/10715762.2012.662276

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

We investigated the effects of hypoxia on inducible NO synthase (iNOS) activity and expression in rheumatoid arthritis (RA) synoviocytes. We further studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions. Human cultured synoviocytes were treated for 24 hours with IL-1 beta, TNF-alpha or neither, and submitted to hypoxia or normoxia for the last 6 hours. Nitrite production and iNOS expression were increased under hypoxia conditions in RA cells in comparison to normoxia. Hypoxia did not potentate the basal and cytokine-induced superoxide productions, while NOXs' subunit expression and p47-phox phosphorylation were increased. Nitrosylation of NOXs and p47-phox was not raised under hypoxia conditions. Finally, peroxynitrite production was significantly increased under hypoxia conditions, in comparison to normoxia. Our results provide evidence for upregulation of iNOS and NOX activities in RA synoviocytes under hypoxia conditions, associated to an increased peroxynitrite production. Synovial cell metabolism under hypoxia conditions might be different from that in normoxia.

引用

页码：628 / 636

页数：9

共 35 条

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