Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.17.1.4 (
xanthine dehydrogenase
)
1,236
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Activated neutrophils cause conversion of
xanthine dehydrogenase
to its oxidase form (xanthine oxidase) in endothelial cells, the mechanism of which may be related to the cytotoxic effect of activated neutrophils. The elastase inhibitors, elastatinal, alpha 1-antitrypsin, and MeO-Suc-(Ala)2-Pro-Val-CH2Cl, significantly inhibited
xanthine dehydrogenase
to oxidase conversion by phorbol myristate acetate-stimulated neutrophils without inhibition of neutrophil adherence to the endothelial cell monolayer. The role of elastase in this enzyme conversion process was confirmed by the ability of purified elastase to cause conversion of
xanthine dehydrogenase
to xanthine oxidase in intact endothelial cells (or cell extracts) without causing cytotoxicity. In contrast,
cathepsin G
failed to cause conversion. The kinetics of conversion induced by elastase was relatively rapid, being essentially completed by 30 min. Upon removal of elastase, the effect was slowly (greater than 12 h) reversible and could be inhibited by cycloheximide treatment. Exposure of endothelial cells to hypoxia failed to enhance the elastase-induced conversion. Treatment of endothelial cells with Ca2+ ionophores failed to cause conversion of
xanthine dehydrogenase
to oxidase, suggesting that intracellular Ca(2+)-activated proteases are not sufficient to induce this process. Neutrophil-induced
xanthine dehydrogenase
to oxidase conversion was inhibited by concomitant treatment with antibodies to CD11b. The results suggest that activated neutrophils induce conversion of
xanthine dehydrogenase
to oxidase by secretion of elastase in close proximity to the endothelial cells and that this intimate contact between the two cell types enables high local concentrations of elastase to be attained, which are sufficient to cause
xanthine dehydrogenase
to xanthine oxidase conversion.
...
PMID:Mechanism of neutrophil-induced xanthine dehydrogenase to xanthine oxidase conversion in endothelial cells: evidence of a role for elastase. 154 Mar 91
A marked decrease in strength, probably due to local collagenolysis, occurs early after surgery in tissues adjacent to an incisional wound. To examine the role of the neutrophils, antineutrophil serum (ANS) was given to rats before and after a standardized end-to-end ileoileal anastomosis. Preimmune serum (PIS) was given to control rats. The decrease in anastomotic breaking strength, amounting to 55% in the PIS group, did not occur in ANS-treated rats, in which there was a decrease by more than 95% in the number of circulating polymorphonuclear cells. The decrease in tissue strength seems to be partly from oxygen free radicals, since the free radical scavengers superoxygen dismutase (SOD) and catalase prevented approximately 50% of the decrease. The xanthine oxidase inhibitor, allopurinol, prevented approximately 30% of the decrease. This is consistent with oxygen free radicals being partly generated by the neutrophils and partly generated after conversion of tissue
xanthine dehydrogenase
to xanthine oxidase. In contrast to ANS, SOD and catalase were unable to fully prevent the decrease in breaking strength. Therefore some other factor in addition to oxygen free radicals should be involved. One such factor may be the release of collagenolytic proteinases, e.g., elastase and
cathepsin G
, from the neutrophils.
...
PMID:Neutropenia prevents decrease in strength of rat intestinal anastomosis: partial effect of oxygen free radical scavengers and allopurinol. 375 86
