Analysis of the MRC showed that at 5 hours, SNP reduced the activity of complex IV by 30%, furthermore, SNP induced depolarisation of the mitochondrial mem brane. In this study we show nothing that NOC 12 induces depolarisation of the mitochondrial membrane as well as SNP, but to a lesser extent, however, it had a more radical effect on MRC activity than SNP, this donor reduces the activities of all the complexes except complex II. These results show that the inhibition of the MRC complexes is not the main cause of cell death induction in chondrocytes by NO. On the other hand, CS activity was increased about 40% in NOC 12 treated chondrocytes, and this fact has been correlated with an increment of the mito chondrial mass, Nisoli and collaborators also suggested that NO is implicated in the regulation of energy metabo lism, possibly through the enhancement of mitochondria formation.
Similar findings were previously found in OA chondrocytes but not in SNP treated ones. Therefore, an increase in mitochondrial mass could be a mechanism by which OA chondrocytes as well as Inhibitors,Modulators,Libraries NOC 12 treated cells, compensate for the electron transfer deficiency resulting from dysfunction in several com plexes and the consequent low production of ATP per mitochondrion, as has already been reported by Maneiro and collaborators. In relation to ATP synthesis both donors had a detri mental effect on it, but once more SNP was the com pound with the most important deleterious effect. With respect to lactate production, SNP reduced the levels in a significant way compared to the control cells, on the con trary, NOC 12 increased lactate production by chondro cytes although this increment was not statistical significant.
Inhibitors,Modulators,Libraries A dysfunction in complexes I, III and IV com promises the electron transfer pathway, this defect could Inhibitors,Modulators,Libraries be solved increasing the anaerobic metabolism to avoid excess production of ROS, and these findings are in agreement with the increase of lactate levels after incuba tion with NOC 12. These results are consistent with the findings reported by Tomita and collaborators on NOC 18 treated chondrocytes, another member of the diaze niumdiolate family. Because NO inhibited the respiration of mitochondria, cellular glycolysis was enhanced significantly, the effect on cellular ATP levels was rather mild, despite the inhibition of mitochondrial respiration by NO.
Thus, the enhanced glycolysis in NOC 18 treated chondrocytes could theoretically com pensate for the inhibition of mitochondrial synthesis by approximately 46%. On Inhibitors,Modulators,Libraries the other hand, the build up of lactic acid will have detrimental effects on the extracel lular matrix and may contribute to the pathogenesis and progression of OA. Chondrocytes are highly glycolytic resident cells of articular cartilage that metabolize glucose as a primary Inhibitors,Modulators,Libraries substrate inhibitor Ixazomib for ATP production.