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.
Borderie
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D
Laboratoire de Biochimie A, Hôpital Cochin, A.P.H.P, Paris, France.
Le Marechal
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H
Ekindjian
O G
OG
Hernvann
A
A
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D009569:Nitric Oxide / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014316:Tritium
D006454:Hemoglobins; D009573:Nitrites; D014316:Tritium; D009599:Nitroprusside; D009569:Nitric Oxide; D019344:Lactic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D003847:Deoxyglucose; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010396:Penicillamine; D005947:Glucose