Abstract
Hypoxanthine (Hx) is produced by hypoxic cells. On reoxygenation the Hx-XOD-reaction generates oxygen free radicals, which are assumed to damage tissues. Since ECs have been reported to contain XOD and are exposed to circulating Hx,they are a likely target for damage. We have studied the effect of Hx and/or XOD on nucleotide metabolism of ECs from human umbilical veins, cultured under standard conditions. Cells in culture wells were labeled overnight with 14C-adenine (100uM), washed and further incubated for 3-6 hr with either Hx (100uM), XOD (40mU/ml) or both. Medium was removed and the cells extracted with perchloric acid. Nucleotides from cells and medium, and Hx, xanthine (X) and uric acid (Ua) from medium were separated by TLC and counted.
In the presence of serum, Hx alone had no effect, but XOD alone caused a 30% fall in cellular nucleotides and an equivalent increase of X+Ua in the medium. In the absence of serum the decrease in nucleotides was 60 to 90%. The combination of Hx + XOD caused a 60-90% (no serum) or 80% (with serum) fall in cellular adenine nucleotides. Thus, endogenous Hx in the presence of exogenous XOD triggers adenine nucleotide catabolism but not vice versa. Serum seems to have a protective role. We conclude that accumulation of Hx alone does not damage ECs, but in the presence of XOD, nucleotide depletion occurs and cellular damage is possible.
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Aalto, K., Raivio, K. EXOGENOUS XANTHINE OXIDASE (XOD) DEPLETES ADENINE NUCLEOTIDES FROM ENDOTHELIAL CELLS (ECs). Pediatr Res 26, 511 (1989). https://doi.org/10.1203/00006450-198911000-00072
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DOI: https://doi.org/10.1203/00006450-198911000-00072