Intracellular metabolism of 4-hydroxynonenal in primary cultures of rabbit synovial fibroblasts.
The intracellular metabolism of 4-hydroxynonenal (HNE), a secondary product of lipid peroxidation and mediator of inflammation, which was found in the joints of patients with rheumatoid arthritis, was investigated in primary cultures of rabbit synovial fibroblasts. A consumption rate of 27.3 nmol/min x 10(6) cells was measured for the cultivated fibroblasts. It could be shown, that 4-hydroxynonenal enters the synovial fibroblasts and is metabolized mainly oxidatively to 4-hydroxynonenoic acid, intermediates of the tricarboxylic acid cycle and water and by 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 incubation. All metabolites accumulates intracellularly within the incubation time except of 4-hydroxynonenal itself. An increase of 4-hydroxynonenoic acid could be detected also extracellularly during the intracellular metabolism of 4-hydroxynonenal. Therefore, an involvement of synovial fibroblasts in the secondary antioxidant defense system of the joints during conditions of higher HNE concentrations like rheumatoid arthritis is suggested.
Ullrich
O
O
Clinic of Physical Therapy, Medical Faculty (Charité), Humboldt University Berlin, Germany.
Huser
H
H
Ehrlich
W
W
Grune
T
T
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts; D005978:Glutathione / Q000378:metabolism; D006880:Hydroxy Acids / Q000378:metabolism; D018384:Oxidative Stress; D011485:Protein Binding; D011817:Rabbits; D013583:Synovial Membrane / Q000378:metabolism*
C091766:4-hydroxy-2-nonenoic acid; D000447:Aldehydes; D006880:Hydroxy Acids; D005978:Glutathione; C027576:4-hydroxy-2-nonenal