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Background: Phosphoribosylpyrophosphate synthetase-1 (PRPS-1; EC 184.108.40.206) is the widely distributed in the human tissues and serves as a regulative key enzyme for purine metabolism, whereas Xanthine Oxidoreductase (XOR; EC 220.127.116.11) is the enzyme responsible for the catabolism of purine nucleotides and might by feed-back mechanism coordinate this entire biochemical pathway. We proposed activation of PRPS-1 and simultaneous inhibition of XOR might initiate regenerative processes after stroke.
Methods: We used hydrogen peroxide intracranial injection (3%) as the model for ROS generation phase of stroke development. XOR activity was measured by evaluation of uric acid formation. PRPS-1 was measured by the kit (Novocib, France). Blood Brain Barrier integrity was evaluated by utility of Evans Blue. KI-67 was used for detection of cells proliferation. ANOVA one-way analysis was used for evaluation of statistical significance of the results. Pearson coefficient was calculated for delineation of the correlation of XOR and PRPS-1 dynamic changes of activities.
Results: PRPS-1 activity after stroke in rats was stimulated by phosphates (control; 1.9145 ± 0.0400 vs phosphates treatment 6.6304 ± 0.0500 vs allopurinol treatment 1.6921 ± 0.0359, p<0.05). In phosphate treated group in comparison with the control XOR activity was lower (control; blank - 0.6406 ± 0.0378; substrate - 0.8513 ± 0.1527; phosphate treatment group blank - 0.2500 ± 7.5758e-3 vs substrate 0.3314 ± 0.0625; allopurinol treated group: blank - 0.5549 ± 8.1301e-3 vs substrate 0.5786 ± 0.017). Ki-67 incorporation was more pronounced in phosphate treated group in comparison with the control. BBB disruption was less in experimental vs control groups.
Conclusion: Phosphates are proposed to be used as the post stroke regenerative agents.