The only donor that induced a significant fall in these values wa

The only donor that induced a significant fall in these values was SNP, with 2 mM SNP at 24 hours, 1. 01 0. 3 versus 2. 30 0. 58. The new generation donor NOC 12 induced a substantial increase in lactate production, with 0. selleck screening library 5 mM NOC 12 at 24 hours, 2. 91 0. 58 versus 2. 30 0. 58, although this increase was not statistically significant. SNP reduces glucose uptake by normal articular chondrocytes Uptake of 2 DG by normal chondrocytes cultured under uM SNP concentrations for either 15 minutes or 1 hour was approximately 20% lower than that found in their respective controls. On the contrary, 2 DG uptake in normal chondro cytes stimulated with NOC 12 did not change relative to the control.

In this set of experiments, uM NO donors concentrations were employed, the reason is because in most of these cases, when mM concentra tions were used, this caused the cells to rise and the quantifications showed false positives. Detrimental effect of NO on chondrocyte viability depends on glucose levels To assess the impact of glucose levels on cell viability after NO treatment, we carried Inhibitors,Modulators,Libraries out experiments with both NO donors using only one constant concentration and increasing glucose concentrations. The percentage of death cells decreased as glucose concentration increased, only when SNP was employed as NO donor. No significant results were found in this issue when NOC 12 was used. Glucose uptake by OA chondrocytes in basal conditions is more efficient than by normal chondrocytes Chondrocytes were maintained for 15 minutes or 1 hour in culture media without glucose and a non metaboliz able analogue of glucose, 2 DG.

Basal 2 DG uptake was identical in normal and OA chondrocytes incubated for 15 minutes, however, the basal 2 DG uptake in OA chondrocytes was significantly higher than in normal Inhibitors,Modulators,Libraries chondrocytes, when cells were maintained for 1 hour in culture. Discussion Traditionally, the increase of endogenous NO produc tion by human articular cartilage has been associated with joint degeneration. NO donors have Inhibitors,Modulators,Libraries been used so far to mimic the OA process in vitro, and they represent a powerful tool of study. However, in vitro models with different NO donors have not resolved what the role of NO is in cartilage degradation due to the lack of unifor mity that exists between the different types of NO com pounds. The differential effects of NO are partly due to the type of NO donors Inhibitors,Modulators,Libraries and cell used.

The biochemistry of NO is complex because of the reactions of NO itself, the interactions of secondary products of NO and the overall chemical environment under which NO is produced. In our study, we employed two NO donor types, the traditional compound SNP, that is used in the majority Inhibitors,Modulators,Libraries of studies, and one diazeniumdiolate, phosphatase inhibitor NOC 12. It has been reported that the traditional donor SNP does not spontaneously release NO in the absence of redox acti vation.

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