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)

Limb remote ischemic postconditioning (LRIP) can reduce ischemia-reperfusion injury (IRI), but its mechanisms are still unclear. We hypothesize that LRIP reduces IRI by reversing eNOS uncoupling. Focal ischemia was induced in Sprague-Dawley rats by middle cerebral artery occlusion for 2 h followed by a 24 h reperfusion. Before this surgery, folic acid (FA) was administered to the drug treatment group by gavage for 11 days. After a 24 h reperfusion, behavioural testing, vascular function, NO concentration and superoxide dismutase activity in the serum were determined. In addition, the infarct size of the brain was also detected. The mRNA of eNOS, nNOS, GTP cyclohydrolase I (GTPCH), P22(phox) and xanthine oxidase (XO) in the ischemic region were detected by RT-PCR, and nitrotyrosine (Tyr-NO2) was detected using Western blot analysis. The results showed that LRIP, FA and FA+LRIP all could improve behavioural score, and increase NO-mediated endothelium-dependent vasomotor responses, reduce infarction of rats subjected to IRI. Western blot and RT-PCR analyses showed that the Tyr-NO2 levels and the mRNA expression of NADPH oxidase catalytic subunit P22(phox) and XO were up-regulated in the ischemic brain, which was significantly inhibited by LRIP, FA and FA+LRIP. The mRNA expression of the rate-limiting enzyme in BH4 synthesis, GTPCH, was down-regulated in the ischemic brain, which could be significantly augmented by LRIP and FA+LRIP. It can be concluded that IRI induces eNOS uncoupling in the cerebral ischemic region and LRIP partially reverses the eNOS uncoupling induced by IRI.
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PMID:Limb remote ischemic post-conditioning reduces brain reperfusion injury by reversing eNOS uncoupling. 2495 90

Hypertension is a highly prevalent disease worldwide. It is known for being one of the most important risk factors for developing cardiovascular disease, including acute myocardial infarction and stroke. Therefore, during the last decades there have been multiple efforts to fully understand the mechanisms underlying hypertension, and then develop effective therapeutic interventions to attenuate the morbidity and mortality associated with this condition. In this regard, oxidative stress has been proposed as a key mechanistic mediator of hypertension, which is an imbalance between oxidant species and the antioxidant defense systems. A large amount of evidence supports the role of vascular wall as a major source of reactive oxygen species. These include the activation of enzymes, such as NADPH oxidase and xanthine oxidase, the uncoupling eNOS and mitochondrial dysfunction, having as a major product the superoxide anion. Among the stimuli that increase the production of oxidative species can be found the action of some vasoactive peptides, such as angiotensin II, endothelin-1 and urotensin II. The oxidative stress state generated leads to a decrease in the biodisponibility of nitric oxide and prostacyclin, key factors in maintaining the vascular tone. The knowledge of the mechanisms mentioned above has allowed generating some therapeutic strategies using antioxidants as antihypertensives with different results. Further studies are required to position antioxidants as key agents in the treatment of hypertension. The current review summarize evidence of the role of oxidative stress in hypertension, emphasizing in therapeutic targets that can be consider in antioxidant therapy.
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PMID:Oxidative stress in hypertension: mechanisms and therapeutic opportunities. 2591 81

Rapamycin is an immunosuppressive agent that is added to drug eluting stents. It prevents restenosis, but it also impairs reendothelialization. Nicorandil is a hybrid agent with adenosine triphosphated (ATP)-sensitive K+ (KATP) channel opener and nitrate properties. It prevents oxidative stress and cell apoptosis induced by rapamycin in endothelial cells in vitro. However, whether nicorandil promotes reendothelialization after angioplasty delayed by rapamycin remains to be determined. Balloon injury model was established in SD rats. Nicorandil increased reendothelialization impaired by rapamycin, and it decreased xanthine oxidase (XO)-generated reactive oxygen species (ROS) induced by rapamycin. In addition, eNOS expression inhibited by rapamycin was increased by nicorandil in vivo. In vitro, rapamycin-impeded cardiac microvascular endothelial cells (CMECs) migration, proliferation and rapamycin-induced ROS production were reversed by nicorandil. Knockdown of XO partially inhibited rapamycin-induced ROS production and cell apoptosis in CMECs, and it promoted CMECs migration and proliferation suppressed by rapamycin. Knockdown of Akt partially prevents eNOS upregulation promoted by nicorandil. The beneficial effect of nicorandil is exhibited by inhibiting XO and up-regulating Akt pathway. Nicorandil combined with rapamycin in effect rescue the deficiencies of rapamycin alone in arterial healing after angioplasty.
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PMID:Delayed reendothelialization with rapamycin is rescued by the addition of nicorandil in balloon-injured rat carotid arteries. 2771 57

There is an unmet need for new strategies to prevent or postpone the development of diabetic kidney disease. The pathophysiology of this condition includes as a central mechanism an imbalance between the excessive production of reactive oxygen species (ROS) and inadequate anti-oxidant defense. Reduction of ROS is therefore an interesting therapeutic target that warrants further investigation. Herein, we review the drivers of oxidative stress in diabetic kidney disease including NADPH oxidases, mitochondrial ROS production, xanthine oxidase, cytochrome P450, uncoupled eNOS and lipoxygenase. Secondly, the role of anti-oxidative mechanisms in diabetic kidney disease is discussed including the role of the kelch-like ECH-associated protein 1- nuclear factor erythroid 2-related factor 2, lipoxin, oral anti-oxidants and glutathione peroxidase-1. We will also review data supporting the concept that the beneficial renal effects of anti-diabetic drugs that target the glucagon-like peptide 1 receptor and the sodium glucose transporter 2 are, at least in part, due to their impact on oxidative stress in diabetic kidney disease. In the present article we critically evaluate both preclinical studies with cell culture experiments and animal models of diabetic kidney disease as well as covering the current findings from clinical studies addressing targeted interventions towards these pathways.
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PMID:Targeting oxidative stress and anti-oxidant defence in diabetic kidney disease. 3244 17


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