Nitric oxide modifies glycolytic pathways in cultured human synoviocytes.

Nitric oxide (NO) is a free radical produced during inflammation following activation of an inducible NO synthase by pro-inflammatory cytokines such as IL-1beta. Since both NO and IL-1beta are involved in the physiopathology of inflammatory arthropathies, we investigated the effects of exogenous NO on glycolytic pathways in cultured human osteoarthritic synovial cells. NO generated from S-nitroso-N-acetyl penicillamine (SNAP) or sodium nitroprusside (SNP) inhibited glucose uptake (by 50% after 1 h of incubation) and lactate production by 16% (SNAP) and 8.5% (SNP) after 3 h. Both NO donors also reduced production of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme of the glycolytic pathway. This effect was reversed by haemoglobin, a NO scavenger with higher affinity for the radical. In contrast, the effect on glucose uptake appeared to be irreversible.