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)

Dopamine can oxidize to form reactive oxygen species and quinones, and we have previously shown that dopamine quinones bind covalently to cysteinyl residues on striatal proteins. The dopamine transporter is one of the proteins at risk for this modification, because it has a high affinity for dopamine and contains several cysteinyl residues. Therefore, we tested whether dopamine transport in rat striatal synaptosomes could be affected by generators of reactive oxygen species, including dopamine. Uptake of [3H]dopamine (250 nM) was inhibited by ascorbate (0.85 mM; -44%), and this inhibition was prevented by the iron chelator diethylenetriaminepentaacetic acid (1 mM), suggesting that ascorbate was acting as a prooxidant in the presence of iron. Preincubation with xanthine (500 microM) and xanthine oxidase (50 mU/ml) also reduced [3H]dopamine uptake (-76%). Preincubation with dopamine (100 microM) caused a 60% inhibition of subsequent [3H]dopamine uptake. This dopamine-induced inhibition was attenuated by diethylenetriaminepentaacetic acid (1 mM), which can prevent iron-catalyzed oxidation of dopamine during the preincubation, but was unaffected by the monoamine oxidase inhibitor pargyline (10 microM). None of these incubations caused a loss of membrane integrity as indicated by lactate dehydrogenase release. These findings suggest that reactive oxygen species and possibly dopamine quinones can modify dopamine transport function.
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PMID:Modification of dopamine transporter function: effect of reactive oxygen species and dopamine. 876 84

Dopamine and structurally related catecholamines in the presence of hydrogen peroxide are oxidized in vitro by xanthine oxidase producing the corresponding melanin pigments. The kinetic parameters of the reaction, measured as aminochrome formation, have been calculated. The rate of peroxidation depends on enzyme and hydrogen peroxide concentration. The optimum pH for the peroxidative activity of the enzyme is around 8.5. Activation of the peroxidative reaction is also elicited by catechol compounds through a redox cycle mechanism. Implications about the possible biochemical relevance of xanthine oxidase activity on catecholamines oxidation are discussed.
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PMID:Catecholamines oxidation by xanthine oxidase. 910 14

Dopamine can form reactive oxygen species and other reactive metabolites that can modify proteins and other cellular constituents. In this study, we tested the effect of dopamine oxidation products, other generators of reactive oxygen species, and a sulfhydryl modifier on the function of glutamate transporter proteins. We also compared any effects with those on the dopamine transporter, a protein whose function we had previously shown to be inhibited by dopamine oxidation. Preincubation with the generators of reactive oxygen species, ascorbate (0.85 mM) or xanthine (500 microM) plus xanthine oxidase (25 mU/ml), inhibited the uptake of [3H]glutamate (10 microM) into rat striatal synaptosomes (-54 and -74%, respectively). The sulfhydryl-modifying agent N-ethylmaleimide (50-500 microM) also led to a dose-dependent inhibition of [3H]glutamate uptake. Preincubation with dopamine (100 microM) under oxidizing conditions inhibited [3H]glutamate uptake by 25%. Exposure of synaptosomes to increasing amounts of dopamine quinone by enzymatically oxidizing dopamine with tyrosinase (2-50 U/ml) further inhibited [3H]glutamate uptake, an effect prevented by the addition of glutathione. The effects of free radical generators and dopamine oxidation on [3H]glutamate uptake were similar to the effects on [3H]dopamine uptake (250 nM). Our findings suggest that reactive oxygen species and dopamine oxidation products can modify glutamate transport function, which may have implications for neurodegenerative processes such as ischemia, methamphetamine-induced toxicity, and Parkinson's disease.
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PMID:Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species. 928 42

We examined the effect of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on extracellular potassium ion concentration ([K(+)](o))-enhanced hydroxyl radical (.OH) generation due to 1-methyl-4-phenylpyridinium ion (MPP(+)) was examined in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused through a microdialysis probe to detect the generation of.OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Induction of KCl (20, 70 and 140 mM) increased MPP(+)-induced.OH formation trapped as 2,3-dihydroxybenzoic acid (DHBA) in a concentration dependent manner. However, the application of L-NAME (5 mg/kg i.v.) abolished the [K(+)](o) depolarization-induced.OH formation with MPP(+). Dopamine (DA; 10 microM) also increased the levels of DHBA due to MPP(+). However, the effect of DA after application of L-NAME did not change the levels of DHBA. On the other hand, the application of allopurinol (20 mg/kg i.v., 30 min prior to study), a xanthine oxidase (XO) inhibitor was abolished the both [K(+)](o)- and DA-induced.OH generation. Moreover, when iron(II) was administered to MPP(+) then [K(+)](o) (70 mM)-pretreated animals, a marked increase in the level of DHBA. However, when corresponding experiments were performed with L-NAME-pretreated animals, the same results were obtained. Therefore, NOS activation may be no relation to Fenton-type reaction via [K(+)](o) depolarization-induced.OH generation. The present results suggest that [K(+)](o)-induced depolarization augmented MPP(+)-induced.OH formation by enhancing NO synthesis.
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PMID:Nitric oxide enhances MPP(+)-induced hydroxyl radical generation via depolarization activated nitric oxide synthase in rat striatum. 1138 16

The purpose of this study was to examine neuroendocrine-disrupting effects of two domestic wastewater aeration lagoons on freshwater mussels. Mussels were caged and placed in two final aeration lagoons for treating domestic wastewaters for 60 days, at a site 1km downstream of the dispersion plume on the eastern shores of the Richelieu River; the western shore served as the reference site. The mussels were analysed for gonad activity, oxidative metabolism of xenobiotics, stress biomarkers and neuroendocrine status (monoamine and arachidonic acid metabolism). The domestic wastewaters produced many different effects at all levels examined. The gonado-somatic index and vitellogenin-like proteins were significantly induced in both aeration lagoons and gonad pyrimidine synthesis (aspartate transcarbamylase activity) was significantly reduced, indicating that vitellogenin-like proteins were produced while DNA synthesis in gametes remained constant. Biomarkers of oxidative metabolism revealed that global heme oxidase (HO), glutathione S-transferase and xanthine (caffeine) oxydoreductase (XOR) activities were significantly induced in at least one of the aeration lagoons, but not downstream of the dispersion plume. The activities of 7-ethoxyresorufin (cytochrome P4501A1), dibenzoylfluorescein (cytochrome P450 3A4 and 3A5) and benzoyloxyresorurufin (cytochrome P450 3A4 and 2B6) dealkylases were readily induced by substances sharing structural similarities with coplanar polyaromatic hydrocarbons and hydroxylated or aminated aromatic or cyclic hydrocarbon compounds such as pharmaceuticals or steroids in the domestic wastewaters. Biomarkers of toxic stress revealed that exposure to aeration lagoons led to increased production of metallothioneins, lipid peroxidation and DNA strand breaks, with decreased heme oxygenase activity. LPO was significantly correlated with XOR, HO and cytochrome P4501A1 activities. Neuroendocrine effects included significant increases in dopamine and serotonin levels and in monoamine oxidase (MAO). Dopamine transport in synaptosome was significantly increased while serotonin transport activity was significantly decreased, suggesting the mussels were in a state of serotonergicity. Moreover, arachidonic acid cyclooxygenase (COX) activity was also readily increased in one aeration lagoon. Aeration lagoons for the treatment of domestic wastewaters are toxic, estrogenic and disrupt the metabolism of monoamines and COX in freshwater mussels.
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PMID:Neuroendocrine disruption and health effects in Elliptio complanata mussels exposed to aeration lagoons for wastewater treatment. 1732 Jan 48