In relation to ATP synthesis both donors had a detri mental effect on it, but once more SNP was the com pound www.selleckchem.com/products/MDV3100.html 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 Inhibitors,Modulators,Libraries the con trary, NOC 12 increased lactate production by chondro cytes although this increment was not statistical significant. A dysfunction in complexes I, III and IV com promises the electron transfer pathway, this defect could 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 Inhibitors,Modulators,Libraries com pensate for the inhibition of mitochondrial synthesis by approximately 46%. On 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 substrate for ATP production.

The Pasteur effect arises in articular cartilage, in this way anaerobic glyco lysis and lactate production Inhibitors,Modulators,Libraries are involved in respiratory metabolism of articular cartilage even under aerobic conditions. An anaerobic metabolism could be beneficial for OA, since the products of glucose degrada tion Inhibitors,Modulators,Libraries would act as ROS scavengers, and would assure Inhibitors,Modulators,Libraries ATP production even under conditions of mitochondrial dysfunction. Only the traditional donor SNP was able to reduce glucose uptake by normal chondrocytes. Previously, we showed that the inhibition of complex IV with sodium azide modified the survival of the chondrocytes, but its effect was greater when glucose was absent. A possible explanation is that the inhibition of complex IV exclu sively is not enough to induce apoptosis and other cellu lar events, such a reduction in the intake of glucose needs to be present to induce it.

The glucose dependency of chondrocytes arises with the fact that the effect of SNP on chondrocyte apoptosis correlates with glucose levels, the lower the glucose levels in the media, the highest the apoptotic levels induced. Finally, OA chondrocytes incorporated more glucose than healthy chondrocytes under the standard experi mental conditions used in this study. These findings are in www.selleckchem.com/products/Vandetanib.html consonance with a higher lactate production by OA chondrocytes than control chondrocytes.