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

Several enzymatic sources of reactive oxygen species (ROS) were described as potential reasons of eNOS uncoupling in diabetes mellitus. In the present study, we investigated the effects of AT1-receptor blockade with chronic telmisartan (25 mg/kg/day, 6.5 weeks) therapy on expression of the BH4-synthesizing enzyme GTP-cyclohydrolase I (GCH-I), eNOS uncoupling, and endothelial dysfunction in streptozotocin (STZ, 60 mg/kg iv, 7 weeks)-induced diabetes mellitus (type I). Telmisartan therapy did not modify blood glucose and body weight. Aortas from diabetic animals had vascular dysfunction as revealed by isometric tension studies (acetylcholine and nitroglycerin potency). Vascular and cardiac ROS produced by NADPH oxidase, mitochondria, eNOS, and xanthine oxidase were increased in the diabetic group as was the expression of NADPH oxidase subunits at the protein level. The expression of GCH-I and the phosphorylation of eNOS at Ser1177 was decreased by STZ treatment. Therapy with telmisartan normalized these parameters. The present study demonstrates for the first time that AT1-receptor blockade by telmisartan prevents downregulation of the BH4 synthase GCH-I and thereby eNOS uncoupling in experimental diabetes. In addition, telmisartan inhibits activation of superoxide sources like NADPH oxidase, mitochondria, and xanthine oxidase. These effects may explain the beneficial effects of telmisartan on endothelial dysfunction in diabetes.
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PMID:AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats. 1853 57

Streptozotocine (STZ) administration (5 mg/100 g) up regulates oxidative (lipid peroxidation as a marker) and nitrosative (protein nitrosilation as a marker) stresses as well as ROS (O(2-), H2O2, OH) generation in heart and aorta in rats after 60 days of STZ action. The level of oxydative stress was higher in aorta. Xanthine oxidase (XO) activation (uric acid as marker), but not lipoxygenase (LTC4 as marker) or cyclooxygenase (TxB2 as marker) are the main oxydases that generate O(2-) as calculated by correlation analysis. STZ administration led to sphingosine pools up regulation in heart and aorta, but pools of polyamines in this organ was down regulated. C27-phytosteroid hormone ecdysterone (100 ng/100 g, per os, 60 days) mimics the action of its structural analog C27-steroid hormone calcitriol (1alpha,25-dihydroxyvitamin D,) and protects rise of ROS generation (by XO inhibition), lipid peroxidation, protein nitrosilation, polyamine degradation in heart and aorta of rats after STZ administration. The new mechanism of iNOS activation, prostaglandine and tetrahydrobiopterin synthesis stimulation by ecdysterone has been proposed. It was due to stimulating enzymatic degradation of sphingosine-1-phosphate as effective regulator of iNOS, COX and GTP-cyclohydrolase in cardio-vascular system: sphingomyelin > ceramide > sphingosine > S-I-P > phosphoethanolamine > ethanolamine.
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PMID:[The inhibition of oxidative and nitrosative stresses by ecdysterone as the mechanisms of its cardio- and vasoprotective action in experimental diabetes type I]. 1905 12