Oxidation of articular cartilage glyceraldehyde-3-phosphate dehydrogenase (G3PDH) occurs in vivo during carrageenin-induced arthritis

Articular cartilage proteoglycan biosynthesis was substantially inhibited by the competitive glycolytic inhibitor 2-deoxyglucose (∼65% at 100 m M), but to a much lesser degree (∼10%) by the oxidative phosphorylation uncoupler, 2,4-dinitrophenol. These results confirm that articular cartilage proteoglycan synthesis mostly utilises ATP which is generated by glycolysis. In addition, we have utilised the loss of the relatively specific labelling of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) by [³H]-iodoacetic acid to show that rabbit articular G3PDH is oxidised in vivo during the animal model of acute arthritis, carrageenin-induced arthritis, in the same way as we have previously shown that cartilage G3PDH is oxidised after in vitro exposure to sublethal doses of H₂O₂. The oxidation of rabbit G3PDH in vivo (18 hr post-injection) corresponds with the maximal influx of PMNL cells into the arthritic synovial fluid [1] and with substantial inhibition of proteoglycan core protein synthesis [2,3]. We propose that H₂O₂ released from "activated" PMNLs and macrophages is responsible for the "down-regulation" of biosynthetic processes found in cartilage during acute inflammation.