Purine Nucleoside Phosphorylase Inhibition Rebalances Purine Metabolism and Attenuates Organ Damage in Sickle Cell Mice.

ABSTRACT: Red blood cells (RBCs) contain the highest purine nucleoside phosphorylase (PNP) level per cell volume, yet the role of PNP in the pathogenesis of sickle cell disease (SCD) is incompletely understood, highlighting an important gap in our knowledge of the disease. Previously, we reported increased PNP release by RBCs and accelerated purine nucleoside metabolism with increased production of pro-oxidant, pro-inflammatory and vasculotoxic byproducts in children with SCD and animal models of hemolytic injury. Thus, we hypothesized that PNP inhibition would reduce hemolysis and attenuate end-organ damage in SCD. In adult patients with SCD (n = 63), plasma PNP levels were markedly elevated compared to controls (n = 27; p < 0.001) and correlated positively with LDH (r = 0.6032, p < 0.0001) and neg

SUBMITTER: Alagbe AE 

PROVIDER: S-EPMC12753582 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature