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)

Two-dimensional gel electrophoretic analysis of cell lysates from Brucella abortus 2308 and the isogenic hfq mutant Hfq3 revealed that the RNA binding protein Hfq (also known as host factor I or HF-I) is required for the optimal stationary phase production of the periplasmic Cu,Zn superoxide dismutase SodC. An isogenic sodC mutant, designated MEK2, was constructed from B. abortus 2308 by gene replacement, and the sodC mutant exhibited much greater susceptibility to killing by O(2)(-) generated by pyrogallol and the xanthine oxidase reaction than the parental 2308 strain supporting a role for SodC in protecting this bacterium from O(2)(-) of exogenous origin. The B. abortus sodC mutant was also found to be much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and the attenuation displayed by MEK2 in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon (IFN-gamma). The attenuation displayed by the B. abortus sodC mutant in both resting and IFN-gamma-activated macrophages was alleviated, however, when these host cells were treated with the NADPH oxidase inhibitor apocynin. Consistent with its increased susceptibility to killing by cultured murine macrophages, the B. abortus sodC mutant also displayed significant attenuation in experimentally infected C57BL6J mice compared to the parental strain. These experimental findings indicate that SodC protects B. abortus 2308 from the respiratory burst of host macrophages. They also suggest that reduced SodC levels may contribute to the attenuation displayed by the B. abortus hfq mutant Hfq3 in the mouse model.
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PMID:The Brucella abortus Cu,Zn superoxide dismutase is required for optimal resistance to oxidative killing by murine macrophages and wild-type virulence in experimentally infected mice. 1584 93

Pro-inflammatory cytokines have been shown to depress myocardial mechanical function by enhancing peroxynitrite generation in the heart. The contribution of NO synthesized by different NOS isoforms, as well as the contribution of superoxide to this mechanism are still not clear. Isolated working hearts of iNOS(-/-) and wildtype mice were perfused for 120 min in the presence or absence of a mixture of pro-inflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma). iNOS mRNA was detected only in cytokine-treated wildtype hearts. In wildtype hearts, cytokine treatment significantly decreased cardiac work, calculated as cardiac output times peak systolic pressure, to 31+/-9% of original values by the end of perfusion (P <0.05). The decline of cardiac work induced by cytokine treatment was significantly reduced in iNOS(-/-) hearts (63+/-5% of original value). Only cytokine-treated wildtype hearts showed decreased aconitase activity, indicating a higher level of oxidative stress in these hearts. Cytokines increased NADPH oxidase activity in both wildtype and iNOS(-/-) hearts, whereas NADH oxidase and xanthine oxidase/xanthine dehydrogenase activities were unaffected. The SOD mimetic MnTE2PyP prevented the cytokine-induced decline of cardiac work in both wildtype and iNOS(-/-) hearts. Cardiac p38 MAPK activation was unaltered in all experimental groups. Although genetic disruption of the iNOS gene provides partial protection against cytokine-induced cardiac dysfunction, iNOS-independent mechanisms, including contribution of NO from other NOS enzymes and the generation of superoxide, are also important contributors.
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PMID:The involvement of superoxide and iNOS-derived NO in cardiac dysfunction induced by pro-inflammatory cytokines. 1617 9

Cyclic AMP (cAMP) is a key intracellular second messenger which at increased levels has been shown to have anti-inflammatory and tissue-protective effects. Its concentration is determined by the activities of both adenylate cyclase (AC) and the phosphodiesterase (PDE) enzymes. The aim of this study was to compare the effects of increased cAMP and glucocorticoid dexamethasone administration on B. melitensis-induced lipid peroxidation, Brucella suppressed antioxidant enzyme activities and PDE4 transcripts in rats. Intracellular cyclic AMP level was elevated by two different approaches; activation of AC and inhibition of PDE activities. Rats were inoculated with B. melitensis for seven days then a single dose of nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX), the adenylate cyclase activator forskolin and dexamethasone were administrated to each infected group, and animals were challenged for 48 h. Brucella-induced lipid peroxidation was significantly reduced by the cAMP elevating agents as well as dexamethasone administration in plasma, liver and spleen. The antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased by the pathogen. Whilst suppressed GSH-Px activity was reversed by cAMP elevating agents, SOD activity was not restored. Superoxide generating enzyme xanthine oxidase activity was not altered at the end of the infection period. Brucella infection increased plasma IL-12 level and this effect was also suppressed by the cAMP elevating agents, whereas TNF-alpha, IFN-gamma and IL-10 levels were unchanged. Intracellular cAMP levels are entirely hydrolyzed by cAMP-specific PDE 4 isozymes (PDE4s) in inflammatory and immunocompetent cells. Brucella reduced mRNA transcript levels for PDE4A by 40%, though PDE4B and 4D transcriptions were being unaffected in spleen. It was concluded that B. melitensis infection decreased activity of the antioxidant defence system, induced lipid peroxidation and suppressed PDE4A transcription. Administration of cAMP elevating agents exhibited similar affect with dexamethasone on lipid peroxidation, IL-12 production and antioxidant enzyme activities in Brucella infection.
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PMID:The effects of increased cAMP content on inflammation, oxidative stress and PDE4 transcripts during Brucella melitensis infection. 1739 85

Diabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45 mg kg(-1), i.p.) injection into rats. Two days after streptozotocin treatment 10 microM kg(-1) day(-1) CAPE was administrated and continued for 60 days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-alpha, 26% for IFN-gamma) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-alpha and IFN-gamma in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.
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PMID:Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats. 1826 48

In this study, we investigated the role of Trypanosoma cruzi invasion and inflammatory processes in reactive oxygen species (ROS) production in a mouse atrial cardiomyocyte line (HL-1) and primary adult rat ventricular cardiomyocytes. Cardiomyocytes were incubated with T. cruzi (Tc) trypomastigotes, Tc lysate (TcTL), or Tc secreted proteins (TcSP) for 0-72 h, and ROS were measured by amplex red assay. Cardiomyocytes infected by T. cruzi (but not those incubated with TcTL or TcSP) exhibited a linear increase in ROS production for 2-48 h postinfection (max 18-fold increase), which was further enhanced by recombinant cytokines (IL-1beta, TNF-alpha, and IFN-gamma). We observed no increase in NADPH oxidase, xanthine oxidase, or myeloperoxidase activity, and specific inhibitors of these enzymes did not block the increased rate of ROS production in infected cardiomyocytes. Instead, the mitochondrial membrane potential was perturbed and resulted in inefficient electron transport chain (ETC) activity and enhanced electron leakage and ROS formation in infected cardiomyocytes. HL-1 rho (rho) cardiomyocytes lacked a functional ETC and exhibited no increase in ROS formation in response to T. cruzi. Together, these results demonstrate that invasion by T. cruzi and an inflammatory milieu affect mitochondrial integrity and contribute to electron transport chain inefficiency and ROS production in cardiomyocytes.
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PMID:Trypanosoma cruzi infection disturbs mitochondrial membrane potential and ROS production rate in cardiomyocytes. 1968 37


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