Abstract
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.
Copyright 2000 Academic Press.
MeSH terms
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Cell Survival / drug effects
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Cells, Cultured
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Deoxyglucose / pharmacokinetics
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Dose-Response Relationship, Drug
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Glucose / metabolism
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Glucose / pharmacokinetics
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Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors
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Glyceraldehyde-3-Phosphate Dehydrogenases / biosynthesis
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Glycolysis / drug effects*
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Hemoglobins / pharmacology
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Humans
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Lactic Acid / biosynthesis
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Nitric Oxide / pharmacology*
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Nitrites / metabolism
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Nitroprusside / metabolism
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Nitroprusside / pharmacology
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Osteoarthritis / metabolism*
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Osteoarthritis / pathology
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Penicillamine / analogs & derivatives
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Penicillamine / metabolism
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Penicillamine / pharmacology
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S-Nitroso-N-Acetylpenicillamine
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Synovial Membrane / cytology
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Synovial Membrane / drug effects*
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Synovial Membrane / metabolism*
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Tritium
Substances
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Hemoglobins
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Nitrites
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Tritium
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Nitroprusside
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Nitric Oxide
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Lactic Acid
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S-Nitroso-N-Acetylpenicillamine
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Deoxyglucose
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Glyceraldehyde-3-Phosphate Dehydrogenases
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Penicillamine
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Glucose