INTRACELLULAR METABOLISM OF 4-HYDROXYNONENAL IN PRIMARY CULTURES OF RABBIT SYNOVIAL FIBROBLASTS

The intracellular metabolism of 4-hydroxynonenal (HNE), a secondary pr oduct of lipid peroxidation and mediator of inflammation, which was fo und in the joints of patients with rheumatoid arthritis, was investiga ted in primary cultures of rabbit synovial fibroblasts. A consumption rate of 27.3 nmol/min x 10(6) cells was measured for the cultivated fi broblasts. It could be shown, that 4-hydroxynonenal enters the synovia l fibroblasts and is metabolized mainly oxidatively to 4-hydroxynoneno ic acid, intermediates of the tricarboxylic acid cycle and water and b y formation of the glutathione-HNE adduct. The share of protein-bound HNE was about up to 8% of the total added HNE after 10 min of incubati on. All metabolites accumulates intracellularly within the incubation time except of 4-hydroxynonenal itself. An increase of 4-hydroxynoneno ic acid could be detected also extracellularly during the intracellula r metabolism of 4-hydroxynonenal, Therefore, an involvement of synovia l fibroblasts in the secondary antioxidant defense system of the joint s during conditions of higher HNE concentrations like rheumatoid arthr itis is suggested. (C) 1997 Elsevier Science Inc.