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)

An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase (MPO; EC 1.11.1.7). The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO (3.5 micrograms per 10(6) nuclei) was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. Still lower levels were found in nuclei from monocytes and a series of human monomyelocytic leukemia cells. MPO from HL-60 cells was purified by immunoaffinity chromatography and fractionated into three components (forms I, II, and III) by CM-cellulose chromatography. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III greater than form II greater than form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during size-exclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.
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PMID:Myeloperoxidase: a myeloid cell nuclear antigen with DNA-binding properties. 282 20

S-Nitrosothiols (RSNO) occur in vivo and have been proposed as nitric oxide (.NO) storage and transport biomolecules. Still, the biochemical mechanisms by which RSNO release .NO in biological systems are not well defined, and in particular, the interactions between reactive oxygen species and RSNO have not been studied. In this work, we show that xanthine oxidase (XO), in the presence of purine (hypoxanthine, xanthine) or pteridine (lumazine) substrates, induces S-nitrosocysteine (CysNO) and S-nitrosoglutathione (GSNO) decomposition under aerobic conditions. The decomposition of RSNO by XO was inhibitable by copper-zinc superoxide dismutase, in agreement with the participation of superoxide anion (O-2) in the process. However, while superoxide dismutase could totally inhibit aerobic decomposition of GSNO, it was only partially inhibitory for CysNO. Competition experiments indicated that O-2 reacted with GSNO with a rate constant of 1 x 10(4) M-1.s-1 at pH 7.4 and 25 degreesC. The decomposition of RSNO was accompanied by peroxynitrite formation as assessed by the oxidation of dihydrorhodamine and of cytochrome c2+. The proposed mechanism involves the O-2-dependent reduction of RSNO to yield .NO, which in turn reacts fast with a second O-2 molecule to yield peroxynitrite. Under anaerobic conditions, CysNO incubated with xanthine plus XO resulted in CysNO decomposition, .NO detection, and cysteine and uric acid formation. We found that CysNO is an electron acceptor substrate for XO with a Km of 0.7 mM. In agreement with this concept, the enzymatic reduction of CysNO by XO was inhibitable by oxypurinol and diphenyliodonium, inhibitors that interfere with the catalytic cycle at the molybdenum and flavin sites, respectively. In conclusion, XO decomposes RSNO by O-2-dependent and -independent pathways, and in the presence of oxygen it leads to peroxynitrite formation.
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PMID:Xanthine oxidase-mediated decomposition of S-nitrosothiols. 952 75

Gouty arthritis is one of the most common rheumatic diseases, and the prevalence continues to rise, which is likely related to increased incidence of comorbidities, lifestyle factors, and suboptimal utilization of urate-lowering therapy. In recent years, multiple new guidelines have been published along with the approval of novel drug therapies. Still, gout remains a poorly controlled disease state that is accompanied by a reduced health-related quality of life, increased health care utilization, and overall negative socioeconomic effects, all of which have a negative impact on patient-related health outcomes. The key to success in gout management is utilization of urate-lowering therapy to prevent recurrence of acute gouty arthritis and to resolve tophi, if present. Xanthine oxidase inhibitors are first-line medications for the prevention of recurrent gout followed by uricosurics, including lesinurad (a uric acid reabsorption inhibitor) as an add-on option. The recent US Food and Drug Administration Safety Communication related to cardiovascular risk with febuxostat may result in increased use of allopurinol in combination therapy with a uricosuric agent such as lesinurad. In this review, we discuss gout management, clinical end points, and patient-related outcomes for consideration, summarize the evidence for combination therapy to achieve serum urate targets, and focus on lesinurad as a novel newer medication for the prevention of gout.
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PMID:Patient considerations in the management of gout and role of combination treatment with lesinurad. 3014 Jan 63

Due to the drastic increase of electricity prosumers, i.e., energy consumers that are also producers, smart grids have become a key solution for electricity infrastructure. In smart grids, one of the most crucial requirements is the privacy of the final users. The vast majority of the literature addresses the privacy issue by providing ways of hiding user's electricity consumption. However, open issues in the literature related to the privacy of the electricity producers still remain. In this paper, we propose a framework that preserves the secrecy of prosumers' identities and provides protection against the traffic analysis attack in a competitive market for energy trade in a Neighborhood Area Network (NAN). In addition, the amount of bidders and of successful bids are hidden from malicious attackers by our framework. Due to the need for small data throughput for the bidders, the communication links of our framework are based on a proprietary communication system. Still, in terms of data security, we adopt the Advanced Encryption Standard (AES) 128 bit with Exclusive-OR (XOR) keys due to their reduced computational complexity, allowing fast processing. Our framework outperforms the state-of-the-art solutions in terms of privacy protection and trading flexibility in a prosumer-to-prosumer design.
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PMID:Data Security and Trading Framework for Smart Grids in Neighborhood Area Networks. 3212 51