Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purine oxidation via XOD formed from XDH in ischemia in an oxidative or proteolytic way is regarded as a source of reactive O2- species. Usually the XOD/XDH ratio is measured to determine the capacity of tissues to form these important inducers of cell damage. But we found that it is difficult to fix the in vivo XOD/XDH ratio, because preparation and measurement time and conditions (absence or presence of SH-protecting agent, of cations) influenced this ratio. A supposed additional proteolytic increase of XOD during the killing procedure could not confirmed.
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PMID:Does the measurement of xanthine oxidase (XOD)/xanthine dehydrogenase (XDH) ratio reflect the actual tissue content of these enzymes? 249 18

Reactive oxygen species play an important role in pathogenesis of a variety of pathological processes, e.g., ischemia-reperfusion, acute viral infections, thermal injury, hepatic diseases, and acute lung injury. Xanthine oxidase (XO) may be a significant source of these cytotoxic oxygen species. We tested the hypothesis that hepatic ischemia-reperfusion releases xanthine dehydrogenase + XO (XDH + XO) into the circulation and that circulating XO damages isolated perfused lung. Isolated liver + lung preparation was perfused with Krebs-Henseleit buffer to minimize confounding effects of circulating neutrophils. In one group, livers were rendered globally ischemic for 2 h and then reperfused (I/R). In another group, livers were pretreated with allopurinol and perfused with buffer containing additional allopurinol (I/R + Allo). After 2 h of ischemia, an isolated lung was connected to liver, and liver + lung preparation was reperfused in series for 15 min. Liver reperfusion was terminated, and lung was recirculated with liver effluent for 45 min. Capillary filtration coefficient (ml.min-1.cmH2O-1.100 g lung dry wt-1) was 2.0 +/- 0.3 and 1.9 +/- 0.4 in control and I/R + Allo lungs, respectively, and 9.0 +/- 1.2 in I/R lungs (P < 0.001). Lung wet-to-dry weight ratio in control and I/R + Allo lungs was 8.6 +/- 0.3 and 9.1 +/- 0.5, respectively, and 14.9 +/- 1.1 in I/R lungs (P < 0.01). Control and I/R + Allo bronchoalveolar lavage protein content was < 1.0 mg/ml compared with 32.6 +/- 8.4 mg/ml in I/R group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase. 761 20

Restoration of blood flow after a period of intestinal ischemia is necessary to maintain cell function and viability; however, the reintroduction of oxygen can initiate a cascade of events that exacerbates tissue injury. Intestinal I-R injury is manifested as increased microvascular and mucosal permeability, and mucosal necrosis. Reperfusion injury begins with the accumulation of hypoxanthine from ATP metabolism and the conversion of XDH to XO during ischemia. Upon reperfusion, the XO catalyzes the conversion of hypoxanthine to superoxide radicals in the presence of oxygen. Superoxide radicals are further reduced to highly reactive hydroxyl radicals, which initiate lipid peroxidation. Lipoperoxidation causes functional and structural alterations in cell membrane lipids and can release numerous inflammatory mediators, which exacerbate tissue damage. Neutrophils are recruited into tissues during ischemia and on reperfusion; then they undergo degranulation and release destructive products (proteases and OFRs), which mediate further tissue injury. A limited number of experimental studies in the gastrointestinal tract of horses have shown I-R injury. Additional studies are necessary to further elucidate and sequence the precise pathophysiologic mechanisms occurring in the equine intestine during I-R. Therapy should be focused on prevention of I-R injury by pharmacologic or chemical inhibition or modification of these pathophysiologic pathways. Selected pharmacologic agents or drug combinations may offer novel, scientifically relevant and yet practical approaches to alleviating intestinal I-R injury in horses. This may improve survival of horses with naturally acquired intestinal strangulation obstruction.
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PMID:Mechanisms of gastrointestinal ischemia-reperfusion injury and potential therapeutic interventions: a review and its implications in the horse. 767 13

Inflammation and ischemia--reperfusion tissue injury are important pathophysiologic processes with a wide spectrum of clinical presentations; the enzyme xanthine dehydrogenase/oxidase (XDH/XO) is thought to play a key role in ischemia--reperfusion injury. Recent studies have shown the transcriptional regulation of XDH/XO by cytokines (Dupont et al., 1992, J. Clin. Invest. 89, 197-202). In the present study, the 5' structure of the XDH/XO gene and characterization of its promoter are undertaken providing an initial step to further elucidate the regulatory mechanism(s) of this enzyme. XDH/XO cDNA from rat bone marrow macrophage has been isolated and used to screen a rat genomic library in order to identify and characterize the promoter of the XDH/XO gene. By Southern analysis, XDH/XO was found to be a single copy gene in the rat genome. Primer extension, RNase protection, and anchor-PCR studies indicate the presence of multiple start sites within a 65 bp window located some 20-85 bp upstream of the translation initiator (ATG). Functional studies of the sequences up to 116 nt upstream of the translational start site, which encompasses the several transcriptional start sites, indicate that this region is sufficient to drive the expression of a luciferase reporter gene and is presumed to represent the promoter. Neither a TATA box nor a GC-rich region are present in close proximity to any of the transcriptional start sites; however, sequences with homology to known initiator elements are found within this 116 bp fragment. Several possible regulatory elements, including a NF-IL6 motif, are also located upstream of the transcriptional start site. This study represents the first description of the XDH/XO promoter from a vertebrate system.
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PMID:Identification of the rat xanthine dehydrogenase/oxidase promoter. 820 9

The release of xanthine oxidase/dehydrogenase XO/XDH (4.99 +/- 1.08 x 10(-12) moles/min/g wet wt in aerobic hearts) was not significantly increased following 30 min of ischemia, but almost doubled following 45 min of ischemia, indicating some endothelial cell damage. This release, however, was small compared to the release induced by digitonin perfusion (26 fold increase in an equivalent volume of effluent) and was nearly 1000 fold less than the enzyme activity measured in the tissue homogenate. There was a significant decrease in cardiac function (heart rate and systolic pressure) following 30 min of ischemia and no recovery of function following 45 min of ischemia and reperfusion. Endothelial cell damage determined by XO/XDH release is negligible during times of ischemia that cause severe damage to myocardial contractility. Coronary endothelial cells should not contribute significantly to circulating XO/XDH levels following ischemia.
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PMID:Xanthine oxidase/dehydrogenase release following ischemia in isolated rat hearts. 830 95

Xanthine dehydrogenase/xanthine oxidase (XDH/XO) is a major cytoplasmic source of superoxide radicals and hydrogen peroxide, and it is considered important in the pathogenesis of ischemia-reperfusion damage. Because little is known about the enzyme in human tissues, the aims of this study were to purify human XDH/XO and to produce Ab for detection of the protein in Western blots and for quantification by ELISA. We purified human milk XDH/XO, produced Ab for Western blotting and ELISA of the protein, and evaluated the molecular forms and activity-protein relationships in human tissues. The molecular size of the purified protein under nondenaturing conditions was approximately 300 kd. On SDS-PAGE, it was fragmented into four main bands of 143, 125, 87, and 59 kd. Ab recognized bands of similar size in Western blots of the purified preparation and human milk. In fresh liver homogenates treated with anti-proteases, the three largest bands were observed; in the intestine, only the two largest were observed. Serum, brain, heart, and skeletal muscle were negative, whereas some lung and kidney samples showed one faint band of 143 kd. Trypsin treatment of the enzyme converted the large molecular-weight bands into smaller bands, as did incubation of a liver homogenate without anti-proteases. XDH/XO protein concentrations (ng/mg total protein) were 146 +/- 70 in liver and 556 +/- 320 in intestine and less than 5 ng/ml in serum. The relationship of activity to protein (2.7-3.0 mumol/min/mg XDH/XO protein) was constant in liver and intestine during development. We conclude that 1) human XDH/XO has molecular size and subunit structure similar to other mammalian enzymes; 2) the polypeptide chain is unstable, also in the intact cell, despite retained activity; and 3) the amount of inactive XDH/XO in human liver and intestine is apparently small.
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PMID:Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein. 856 97

Diabetic patients exhibit dysfunction of the normal wound healing process, leading to local ischemia by vascular occlusive disease as well as sustained increases in the proinflammatory cytokines and overproduction of reactive oxygen species (ROS). Of the many sources of ROS, the enzyme xanthine oxidase (XO) has been linked to overproduction of ROS in diabetic environment, and studies have shown that treatment with XO inhibitors decreases XO overactivity and XO-generated ROS. This study evaluates the role of XO in the diabetic wound and the impact of specifically inhibiting its activity on wound healing. Treatment of diabetic wounds with siXDH (xanthine dehydrogenase siRNA) decreased XDH mRNA expression by 51.6%, XO activity by 35.9%, ROS levels by 78.1%, pathologic wound burden by 31.5%, and accelerated wound healing by 7 days (23.3%). Polymerase chain reaction analysis showed that increased XO activity in wild-type wound may be due to XDH to XO conversion and/or XO phosphorylation, but not to gene transcription, whereas increased XO activity in diabetic wounds may also be from gene transcription. These results suggest that XO may be responsible for large proportion of elevated oxidative stress in the diabetic wound environment and that normalizing the metabolic activity of XO using targeted delivery of siXDH may decrease overproduction of ROS and accelerate wound healing in diabetic patients.
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PMID:Normalizing dysfunctional purine metabolism accelerates diabetic wound healing. 2557 64

Oxidative stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS)-2 have been shown in the pathogenesis of liver ischemia-reperfusion (IR) injury. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression therefore this study determined the role of selective N-SMase inhibition on nitrative and oxidative stress markers following liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Nitrative and oxidative stress markers were determined by evaluating NOS2 expression, protein nitration, nitrite/nitrate levels, 4-hydroxynonenal (HNE) formation, protein carbonyl levels and xanthine oxidase/xanthine dehydrogenase (XO/XDH) activity. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reaction monitoring method using ultra-fast liquid chromatography coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. NOS2 expression, nitrite/nitrate levels and protein nitration were significantly greater in IR injury and decreased with N-SMase inhibition. Treatment with a selective N-SMase inhibitor significantly decreased HNE formation, protein carbonyl levels and the hepatic conversion of XO. Data confirm the role of nitrative and oxidative injury in IR and highlight the protective effect of selective N-SMase inhibition. Future studies evaluating agents blocking N-SMase activity can facilitate the development of treatment strategies to alleviate oxidative injury in liver I/R injury.
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PMID:Inhibition of neutral sphingomyelinase decreases elevated levels of nitrative and oxidative stress markers in liver ischemia-reperfusion injury. 2707 55