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)

In vivo electron paramagnetic resonance (EPR) with nitroxyl spin probes has been used for the evaluation of in vivo free radical reactions and redox status in living animals. The aim of this study was to clarify the location of free radical reactions induced by hyperglycemia in osteogenic disorder shionogi (ODS) rats using in vivo EPR spectroscopy. Diabetes was induced by intravenous injection of streptozotocin (STZ). The amount of ascorbic acid (AsA) in ODS rats was controlled by feeding AsA-containing water. Fourteen days after STZ injection, blood glucose and plasma malondialdehyde levels in STZ-treated rats significantly increased compared with untreated rats. Signal decay rates of intravenously injected 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (carbamoyl-PROXYL) (less membrane permeable) and 3-carboxy-PROXYL (membrane impermeable) were enhanced in STZ-treated rats in agreement with the previous reports. The decay rate of 3-acetoxymethoxy-PROXYL (membrane permeable) was significantly enhanced by STZ treatment in AsA-depleted rats, and this enhancement was partially restored to the control value by xanthine oxidase inhibitor, although the rate in AsA-supplemented rats was not changed by STZ treatment. These results suggested that the enhancement of signal decay occurred mainly in the intravascular region in STZ-induced diabetic rats and that AsA depletion induced the enhancement of intracellular signal decay through xanthine oxidase, although it is not clear whether the enhancement of signal decay is the cause or the effect of STZ-induced diabetes.
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PMID:In vivo measurement of redox status in streptozotocin-induced diabetic rat using targeted nitroxyl probes. 1513 Feb 87

The osteoporosis that occurs with aging is associated with reduced number and activity of osteoblastic cells. Aging, menopause, and osteoporosis are correlated with increased oxidative stress and reduced antioxidant defense mechanisms. We previously demonstrated that oxidative stress induced by a variety of compounds such as xanthine/xanthine oxidase (XXO) and minimally oxidized LDL (MM-LDL) inhibit the osteogenic differentiation of osteoprogenitor cells. Oxysterols are a family of products derived from cholesterol oxidation that have important biological activities. Recently, we reported that a specific oxysterol combination consisting of 22(S)- or 22(R)-hydroxycholesterol and 20(S)-hydroxycholesterol has potent osteogenic properties in vitro when applied to osteoprogenitor cells including M2-10B4 (M2) marrow stromal cells. We now demonstrate that this osteogenic combination of oxysterols prevents the adverse effects of oxidative stress on differentiation of M2 cells into mature osteoblastic cells. XXO and MM-LDL inhibited the osteogenic differentiation of M2 cells, demonstrated by the inhibition of markers of osteogenic differentiation: alkaline phosphatase activity, osteocalcin expression and mineralization. Treatment of M2 cells with osteogenic oxysterol combination 22(S)- and 20(S)-hydroxycholesterol both blocked and reversed the inhibition of osteogenic differentiation produced by XXO and MM-LDL in these cells. The protective effect of the oxysterols against oxidative stress was dependent on cyclooxygenase 1 and was associated with the osteogenic property of the oxysterols. These findings further demonstrate the ability of the osteogenic oxysterols to positively regulate osteogenic differentiation of cells, and suggests that the use of these compounds may be a novel strategy to prevent the adverse effects of oxidative stress on osteogenesis.
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PMID:Osteogenic oxysterols inhibit the adverse effects of oxidative stress on osteogenic differentiation of marrow stromal cells. 1588 Jul 3

MC3T3-E1 osteoblast-like cells represent a suitable model for studying osteogenic development in vitro. The current investigation extends our previous work on the response of these cells to hydrogen peroxide by considering the effects of reactive oxygen species from other sources, and by determining whether differentiation alters sensitivity to oxidative damage. Aspects of hydrogen peroxide-mediated apoptotic and necrotic death were also examined. Cell viability was determined using the Alamar Blue assay; and accompanying morphological changes monitored by phase-contrast microscopy. Sensitivity to hydrogen peroxide increased significantly in cultures which had been induced to differentiate. Hydrogen peroxide and copper (II) ions, when combined, produced greater damage than hydrogen peroxide alone, whilst the hydroxyl radical scavengers mannitol or dimethylsulphoxide had no effect. Cyclosporin A and nicotinamide afforded partial protection. The tryptophan metabolite, 3-hydroxykynurenine significantly reduced viability, although 3-hydroxyanthranilic acid did not. The xanthine/xanthine oxidase system also reduced cell viability, an effect prevented by catalase but potentiated by superoxide dismutase. S-nitroso-N-acetylpenicillamine did not impair viability at the concentrations tested. Cultures were resistant to mitochondrial poisoning by potassium cyanide, but succumbed to 24-h exposures to 3-nitropropionic acid (1 mM). The results reveal a differential sensitivity of MC3T3-E1 cells to hydrogen peroxide-induced oxidative stress, an enhancement of sensitivity by cellular differentiation, and a potential preference for the glycolytic pathway by MC3T3-E1 cells. This study gives new insight into how bone cells may succumb to the toxic effects of oxidative stress generated by different stimuli and has relevance to conditions such as osteoporosis.
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PMID:Responses of differentiated MC3T3-E1 osteoblast-like cells to reactive oxygen species. 1844 93

Oxidative stress may play a major role in age-related osteoporosis in part by inhibiting osteoblast generation from osteoprogenitors cells. In the present study, we hypothesized that oxidative stress may inhibit the osteogenic differentiation of bone marrow stromal cells (MSC) in part by inhibiting the Hedgehog (Hh) signaling pathway, which is essential for bone development and maintenance and induces osteogenic differentiation of osteoprogenitor cells. To test this hypothesis, we examined the effects of oxidative stress on Sonic Hh (Shh)-induced osteogenic differentiation and signaling in M2-10B4 (M2) MSC, C3H10T1/2 embryonic fibroblasts, and mouse primary MSC. Treatment of cells with H(2)O(2) inhibited Shh-induced osteogenic differentiation determined by the inhibition of Shh-induced expression of osteogenic differentiation markers alkaline phosphatase (ALP), osterix (OSX), and bone sialoprotein (BSP). Similar effects were found when oxidative stress was induced by xanthine/xanthine oxidase (XXO) or minimally oxidized LDL (MM-LDL). H(2)O(2) , XXO, and MM-LDL treatment inhibited Shh-induced expression of the Hh target genes Gli1 and Patched1 as well as Gli-dependent transcriptional activity in M2 cells. H(2)O(2) treatment also inhibited Hh signaling induced by the direct activation of Smoothened by purmorphamine (PM), but not by Gli1 overexpression. This suggests that oxidative stress may inhibit Hh signaling upstream of Gli activation and Gli-induced gene expression. These findings demonstrate for the first time that oxidative stress inhibits Hh signaling associated with osteogenic differentiation. Inhibition of Hh signaling-mediated osteogenic differentiation of osteoprogenitor cells may in part explain the inhibitory effects of oxidative stress on osteoblast development, differentiation, and maintenance in aging.
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PMID:Hedgehog signaling and osteogenic differentiation in multipotent bone marrow stromal cells are inhibited by oxidative stress. 2071 24