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

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we demonstrated that NO synthase (cNOS) and xanthine oxidase (XO) of human keratinocytes can be activated to release NO, superoxide (O2-) and peroxynitrite (ONOO-) following exposure to ultraviolet B (UVB) radiation. We defined that this photo induced response may be involved in the pathogenesis of sunburn erythema and inflammation. Treatment of human keratinocytes with UVB (290-320 nm) radiation (up to 200 mJ/cm2) resulted in a dose-dependent increase in NO and ONOO- release that was inhibited by N-monomethyl-L-arginine (L-NMMA). NO and ONOO- release from keratinocytes was accompanied by an increase in intracellular cGMP levels. Treatment of human keratinocyte cytosol with various doses of UVB (up to 100 mJ/cm2) resulted in an increase in XO activity that was inhibited by oxypurinol. UVB radiation (up to 100 mJ/cm2) of keratinocytes resulted in a 15-fold increase in S-nitrosothiol formation, which directly increased purified soluble guanylate cyclase (sGC) activity by a mechanism characteristic of release of NO from a carrier molecule. In reconstitution experiments, when UVB-irradiated (20 mJ/cm2) purified cNOS isolated from keratinocyte cytosol was combined with UVB-irradiated (20 mJ/cm2) purified XO, a 4-fold increase in ONOO- production, as compared to nonirradiated enzymes, was observed. ONOO- synthesized by NO and O2- following UVB radiation of cNOS and XO was inhibited by oxypurinol (100 microM). UVB radiation of keratinocyte cytosol resulted in an increase in oxygen free radical production, consistent with the increased production of ONOO- by UVB-irradiated keratinocyte cytosol. In in vivo experiments, when experimental animals were subjected to UVB radiation, a protection factor (PF) of 6.5 +/- 1.8 was calculated when an emulsified cream formulation containing nitro-L-arginine (L-NA) (2%) and L-NMMA (2%) was applied to their skin. The present study indicates that UVB radiation acts as a potent stimulator of cNOS and XO activities in human keratinocytes. NO and ONOO- may exert cytotoxic effects in keratinocytes themselves, as well as in their neighboring endothelial and smooth muscle cells. This may be a major part of the integrated response leading to erythema production and the inflammation process.
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PMID:Alterations of nitric oxide synthase and xanthine oxidase activities of human keratinocytes by ultraviolet B radiation. Potential role for peroxynitrite in skin inflammation. 868 88

Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.
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PMID:Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats. 948 4

Intracellularly generated reactive species of both oxygen (ROS) and nitrogen (RNS) have been implicated in signaling responses in airway epithelial cells, but these radicals have not been measured directly in such cells. In this study, intracellular production of both ROS and RNS were measured in the same cell lysates of guinea pig tracheal epithelial (GPTE) cells maintained in primary culture. ROS and RNS were quantified under basal (constitutive) conditions and in response to different stimuli: LPS and TNFalpha [activators of inducible nitric oxide synthase (iNOS)]; several activators of calcium-dependent cNOS (ATP, bradykinin, ionophore A23187, and thapsigargin); and exogenous oxidant stress generated by addition of xanthine oxidase to purine (p + XO). Studies with LPS and TNFalpha also were performed using the murine macrophage cell line, RAW 264.7, as a positive control. Intracellular oxidant production was detected from oxidation of dihydrorhodamine to rhodamine. NOx was quantified by either chemiluminescent or fluorescent detection. NOS activity was measured as citrulline production from arginine. Basal production of oxidants by GPTE cells (0.08 + 0.00 nmol rhodamine) was less than 10% that of RAW.267 cells (0.91 + 0.03 nmol rhodamine). TNFalpha and LPS significantly increased intracellular oxidant production in GPTE cells, as did p + XO, but none of the cNOS activators affected production of oxidants in these cells. Concentrations of NO2 after 4 h in unstimulated RAW 264.7 and GPTE cells were similar and comprised 63% of total NOx in GPTE and 62% in RAW cells. TNFalpha and LPS both increased NO2 in GPTE cells, but none of the Ca++-mobilizing agents nor p + XO significantly affected intracellular RNS. The results suggest both ROS and RNS can be measured in the same lysates from airway epithelial cells, and that both ROS and RNS are produced in these cells in response to different stimuli.
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PMID:Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro. 958 18

Alcohol consumption and cigarette smoking are two etiologic factors that have a close relationship with peptic ulcer diseases. Chronic active gastritis is reportedly associated with chronic alcohol ingestion. Nonetheless, the inflammatory changes are likely to be related to concurrent Helicobacter pylori infection that is common among alcoholics. Moreover, chronic alcoholism is also correlated with the presence of gastric metaplasia. Both clinically and experimentally, alcohol had been shown to affect the mucosal barrier and histology. These ulcerogenic effects play a crucial role in altering gastric mucosal defense mechanisms. Cigarette smoking is coupled with the initiation and prolongation of gastric ulcers. Epidemiologic data show that cigarette smoking increases both the incidence and relapse rate of peptic ulcer diseases and also delays ulcer healing in humans. Retrospective studies also indicate that cigarette smoking is a key factor in inducing ulcer diseases rather than a linked behavior. The general detrimental effects of cigarette smoking in the gastric mucosa include reduction of circulating epidermal growth factor, increase in tissue free radical production and the presence of free radicals in smoke, together with reduction of mucosal constitutive nitric oxide synthase activity. Furthermore, the alteration of normal gastric mucosal blood flow and angiogenesis and the suppression of cell proliferation contribute largely to the delay in ulcer healing in cigarette smokers. Concurrent consumption of alcohol and cigarette smoking significantly increases the risk of gastric ulcers. In animal experiments, cigarette smoking potentiated ethanol-induced gastric mucosal damage. The reduction of mucus secretion, increase in leukotriene B4 level, increased activities of inducible nitric oxide synthase, xanthine oxidase and myeloperoxidase, and the expression of adhesion molecules in the gastric mucosa accompanied such potentiating effects. Substances other than nicotine in cigarette smoke may also contribute to the above effects.
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PMID:Alcohol drinking and cigarette smoking: a "partner" for gastric ulceration. 1119 34

Nitric oxide (NO) was found to modulate uric acid production through its influence on xanthine oxidase activity, and a close circadian relationship of serum uric acid (SUA) and NO was reported. Studies also revealed that serum NO activity could be determined by endothelial constitutive nitric oxide synthase gene (ecNOS) polymorphism. This study was designed to investigate whether SUA could be influenced by a 27-bp repeat polymorphism in intron 4 of ecNOS gene. A total of 398 nondiabetic subjects and 800 patients with type 2 diabetes were studied. The ecNOS gene intron 4 polymorphism was determined by polymerase chain reaction (PCR). The mean SUA level of patients having type 2 diabetes was significantly lower than that of control subjects (6.1 +/- 1.8 mg/dL v 6.6 +/- 1.8 mg/dL, P<.001); and the mean SUA level of diabetic patients with ecNOS ab/aa genotypes was lower than that of patients with bb genotype (5.7 +/- 1.6 mg/dL v 6.2 +/- 1.8 mg/dL, P=.008). When subgrouped by gender, the SUA of female diabetic subjects was found to be significantly associated with ecNOS genotype. Using Pearson's correlation analysis and multiple linear regression analysis, ecNOS genotype was noticed to be an independent factor in contributing to SUA variability in female diabetic patients. Our results suggest that SUA levels may be associated with NO activity and can be genetically predetermined.
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PMID:Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with serum uric acid levels in Chinese subjects with type 2 diabetes. 1462 5

Endothelium-dependent and endothelium-independent reactions of relaxations of vascular smooth muscle (VSM) were examined in the aorta preparations of the two groups (6-8 and 21-22 month). The studies also two NO synthase (NOS) isoform activity--inducible (iNOS) and constitutive (cNOS), activity of arginase and nitrate reductase and the content of high-molecular nitrosothiols (HMNT) and low-molecular nitrosothiols (LMNT) and stable metabolites of NO (NO(-)2, NO(-)3). Aging rats demonstrated only endothelium-dependent responses of VSM to acethylcholine lowering. This endothelial dysfunction depend on high activity of arginase, iNOS and salvage (by nitrate reductase) NO synthesis, both reactive oxigen species (ROS) (by xanthine oxidase) and peroxynitrite generation, as well as low activity of constitutive (eNOS, nNOS) NO synthesis. Angiotensin-converting enzyme inhibitor (enalapril) administration (20 mg/kg, 30 or 55 days) up regalate constitutive NO synthesis by arginase, iNOS, nitrate reductase activity and ROS and peroxynitrite generation inhibition thus restore endothelium-dependent relaxations of VSM in aging rats. The result obtained suggest a new roles for the renin-angiotensin system in vascular tone regulation. Thus enalapril might serve as a novel tool to prevent aging-associated endothelial dysfunction.
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PMID:[Effect of enalapril on nitric oxide synthesis, oxidative metabolism, and vascular tone in aging rats]. 1790 67

In this study, we examined the protective effects of vitamin E (VE) against gastric mucosal lesions induced by water immersion restraint stress (WIRS) in rats in comparison with that of vitamin C (VC). The gastric mucosa of rats with 6 h of WIRS showed lesions with bleeding, decrease in nonprotein SH, VC, VE, and adherent mucus concentrations and constitutive nitric oxide synthase activity, and increase in lipid peroxide and NOx (nitrite/nitrate) concentrations and myeloperoxidase, xanthine oxidase, and inducible nitric oxide synthase activities. Either VE (0.05 or 0.5 mmol/kg) or VC (0.5 or 1.5 mmol/kg) was orally administered to rats with 6 h of WIRS just before the onset of the stress. Both doses of pre-administered VE prevented gastric mucosal lesion development and attenuated all these changes in gastric mucosal components and enzymes studied, whereas only the higher dose of pre-administered VC suppressed the changes in all parameters studied. These results indicate that orally administered VE protects against WIRS-induced gastric mucosal lesions in rats more effectively than orally administered VC. These results also suggest that the administered VE protects against gastric mucosal lesions in rats with WIRS through its antioxidant and anti-inflammatory actions in the gastric mucosa in the same way as the administered VC.
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PMID:Vitamin E protects against stress-induced gastric mucosal lesions in rats more effectively than vitamin C. 2009 2

In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min) of myocardium it was investigated changes of biochemical processes in arterial blood at intragastric introduction of medicinal form (tablets) of flocalin (the fluorine-containing opener of ATP-sensitive potassium channels) in a dose 2,2 mg/kg. The data analysis allowed to define a few possible mechanisms of cardioprotective action offlocalin, which prevented the opening of a mitochondrial permeability transition pore (MPTP) and inhibition of apoptosis induced by it. They consist, from one side, in activating of the constitutive de novo biosynthesis of nitric oxide by cNOS, from other side, in suppression of inducible nitric oxide de novo synthesis by iNOS in such way to prevent the formation of toxic peroxynitrite by co-operation of surplus nitric oxide with superoxide anion, thereby limits the generation of toxic active forms of nitrogen (*NO2) and oxygen (*OH). The first effect of flocalin takes place due to limitation the degradation of L-arginine by arginase which keeps substrat for cNOS, second--due to the inhibition of superoxide generation, in particular, by xanthine oxidase (marker uric acid), lipoxigenase (marker LTC4) and cyclooxygenase (marker TxB2). Because LTC4 have coronaroconstrictory, arrhythmogenic and chemoattractory properties in the conditions of myocardial ischemia, inhibition of its production both with superoxide generation (markers H2O2 and diene conjugates) may be the another mechanisms of flocalin's cardioprotection. Powerful antiischemic action of flocalin (marker nitrite anion) as the mechanisms of cardioprotection is possible as well as inhibition of ATP and GTP degradation (marker hypoxanthine+xanthine+inosine levels in the blood) and, possibly, stimulation ofhaem degradation by haem oxygenase (markers total bilirubin and Fe in the blood). Diminishing content of free arachidonic acid in arterial blood can testify inhibition of cellular membranes phospholipides degradation by phospholipase A2 as a result of flocalin cardioprotection.
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PMID:[Biochemical mechanisms of the cardioprotective effect of the K(ATP) channels opener flocalin (medicinal form) in ischemia-reperfusion of myocardium]. 2417 72

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