Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured rat mesangial cells were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on their metabolism of arachidonic acid (AA). Cell viability, as assessed by 51Cr release, was not affected by the concentrations of xanthine plus xanthine oxidase used. Prostaglandin E2 (PGE2) production following exposure to increasing quantities of xanthine plus xanthine oxidase was significantly decreased to 38.1 +/- 9.7 or 30.8 +/- 6.9% of control levels (P less than 0.05) when cells were stimulated with the calcium ionophore A23187 (1 microgram/ml) or AA (10(-6) M), respectively. Maximum suppression of production was seen within 10 min of ROS exposure. Thromboxane B2 production was similarly decreased to 83.1 +/- 7.6 (0.05 less than P less than 0.10) or 54.9 +/- 2.5% (P less than 0.05). This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase or mannitol, which suggested that H2O2 was the responsible metabolite. High levels of H2O2 (5 x 10(-4) M) suppressed PGE2 production to 44.0 +/- 4.1 or 17.4 +/- 6.2% of A23187- or AA-stimulated production (P less than 0.05). Lower levels of H2O2 resulted in significant stimulation of base-line PGE2 production. Analysis of release of [3H]AA-labeled metabolites from A23187-stimulated cells showed no effect of H2O2 on phospholipase activity. Thus ROS can stimulate or inhibit AA metabolism in the glomerular mesangium, which may have important effects on glomerular hemodynamics during glomerular injury.
 ...
PMID:Biphasic effect of oxygen radicals on prostaglandin production by rat mesangial cells. 310 32

Thromboxane B2 biosynthesis from arachidonic acid was increased in platelets from hypercholesterolemic rabbits. The enzymic activity of phospholipase A2 which releases arachidonic acid, the precursor for the biosynthesis of thromboxane B2, showed hardly any change in hypercholesterolemic platelets. Phospholipase C and diglyceride lipase activities also were not changed in platelets from hypercholesterolemic rabbits. Furthermore, phospholipid concentration in platelets were not increased in this state. Thus, I conclude that the supply of precursor for thromboxane B2 biosynthesis was not increased in platelets from hypercholesterolemic rabbits as compared to controls. I have clarified this mechanism for the increased thromboxane synthesis. The biosynthesis of prostaglandin H2 and thromboxane B2 were unaffected by superoxide dismutase, xanthine, xanthine oxidase, mannitol, or benzoate in the experiments designed to study the possible involvement of reactive oxygen species. The effect of glutathione, glutathione peroxidase and H2O2 on cyclooxygenase and thromboxane synthetase were studied by using partially purified enzymes and platelet microsomes. Glutathione and glutathione peroxidase inhibited the activity of the cyclooxygenase but did not inhibit that of thromboxane synthetase. H2O2 caused the inactivation of cyclooxygenase, but the addition of H2O2 did not inhibit the formation of thromboxane B2 from prostaglandin H2. An examination of glutathione concentration and glutathione peroxidase activity in platelets from normal and experimentally hypercholesterolemic rabbits demonstrated that both were decreased in platelets from latter group. The observed alterations in glutathione levels and glutathione peroxidase activity are large enough to cause increased thromboxane B2 synthesis in platelets but the possibility that other unidentified factors may also contribute cannot be excluded.
 ...
PMID:Thromboxane synthesis in hypercholesterolemic platelets--on the mechanism of increased thromboxane synthesis. 661 25