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  • Title: Concurrent generation of nitric oxide and superoxide inhibits proteoglycan synthesis in bovine articular chondrocytes: involvement of peroxynitrite.
    Author: Oh M, Fukuda K, Asada S, Yasuda Y, Tanaka S.
    Journal: J Rheumatol; 1998 Nov; 25(11):2169-74. PubMed ID: 9818660.
    Abstract:
    OBJECTIVE: Nitric oxide (NO), widely assumed to be a mediator of interleukin 1 (IL-1), inhibits proteoglycan synthesis in articular chondrocytes. IL-1 also produces superoxide anion. We hypothesized that the IL-1 inhibited proteoglycan synthesis is the result of peroxynitrite formed by the reaction of NO with superoxide. METHODS: Bovine articular chondrocytes were cultured in the presence of SIN-1, which leads to simultaneous generation of both NO and superoxide. Proteoglycan synthesis was measured based on the incorporation of [35S] sulfate, and the presence of peroxynitrite was confirmed using immunohistochemistry. RESULTS: SIN-1 inhibited proteoglycan synthesis and superoxide dismutase reversed SIN-1 inhibited proteoglycan synthesis, indicating the simultaneous generation of superoxide is essential to inhibit proteoglycan synthesis. IL-1 induced peroxynitrite in articular chondrocytes and addition of peroxynitrite inhibited proteoglycan synthesis. CONCLUSION: The concurrent generation of superoxide anion and NO is required for the action of IL-1 to inhibit proteoglycan synthesis. Peroxynitrite is a candidate for this underlying mechanism.
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