Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DT diaphorase is a flavoprotein that enzymatically transfers two electrons from quinones as intermediate substrates and has been reported to increase its activity in the liver after exposure to toxicants. In this series of experiments, we tested the hypothesis that DT diaphorase also increases its activity after exposure to oxidants following gradient ischemia in skin. Using dorsal rat flaps, oxidant stress was induced immediately or during a 7-day period of preconditioning as a bipedicle flap before the distal attachment was divided. DT diaphorase activity (delta Abs/min/100 g) or expression of message was measured during the period of preconditioning to determine the relationship between skin survival, enzyme activity, and expression of message. There was 4.7 +/- 0.8 cm of skin necrosis in the distal end of acute flaps while the preconditioned flaps had no skin necrosis after the distal attachment was divided. In the acute flaps, the DT diaphorase activity was equal throughout the flap for the first 6 hr. After 24 hr of ischemia, the DT diaphorase activity was significantly higher in the proximal end of the flap (1.83 +/- 0.21 delta Abs/min/100 g) than that in the distal end (0.005 +/- 0.01 delta Abs/min/100 g), which was significant (P < 0.05). In the preconditioned flaps, enzyme activity did not increase but there was as 50-fold increase in DT diaphorase activity at the distal end 24 hr after they were divided (P < 0.05). Maximal enzyme induction of DT diaphorase activity occurred after 4 days of preconditioning and correlated with the maximal expression of mRNA. These studies provide the first evidence that DT diaphorase enzyme activity is inducible after oxidant stress. The data also suggests that DT activity remains elevated for at least 6 hr of ischemia and may be a potential source of anti-oxidant activity in ischemic skin.
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PMID:dT diaphorase: increased enzyme activity and mRNA expression in oxidant stress of skin. 815 25

Blockade of nitric oxide synthase (NOS) activity in the developing nervous system may protect the brain from hypoxic-ischemic insult. We determined the efficacy in 7 day old rat pups of systemically administered cysteamine in reducing neuronal NOS and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivities and protection of the brain from an hypoxic-ischemic insult. Cysteamine reversibly reduced NOS immunoreactivity at 2 h after an intraperitoneal injection of 200 mg/kg. NADPH-diaphorase histochemical reactivity was reduced after 300 mg/kg but all animals had generalized seizures and succumbed to the hypoxia-ischemia. At lower doses, despite the blockade of NOS immunoreactivity, there was no difference in the number of injured animals compared to controls. These results demonstrate that NOS immunoreactivity does not represent all of NADPH-diaphorase reactivity and that blockade of this activity with cysteamine is not protective.
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PMID:Cysteamine eliminates nitric oxide synthase activity but is not protective to the hypoxic-ischemic neonatal rat brain. 884 8

Administration of inhibitors of neuronal nitric oxide synthase or deletion of the encoding gene in rodents provided evidence that neuronal nitric oxide synthase activity may contribute to neuronal cell death following global and focal cerebral ischemia. In the present study, we investigated by in situ hybridization the expression of an endogenous inhibitor of neuronal nitric oxide synthase activity, designated protein inhibitor of neuronal nitric oxide synthase and homologous to cytoplasmic dynein light chain, in the post-ischemic rat brain. Following global ischemia induced by cardiac arrest, messenger RNA expression of protein inhibitor of neuronal nitric oxide synthase was rapidly induced in pyramidal neurons of the hippocampal CA3 region and granule cell of the dentate gyrus which are resistant to ischemic damage. In vulnerable CA1 pyramidal neurons however, protein inhibitor of neuronal nitric oxide synthase expression remained at basal level after global ischemia and was associated with an increase in nicotinamide adenine dinucleotide phosphate-diaphorase activity and subsequent DNA fragmentation indicating ischemia-mediated neuronal cell death. Following focal cerebral ischemia induced by permanent occlusion of the middle cerebral artery, transcripts of protein inhibitor of neuronal nitric oxide synthase progressively accumulated in cortical neurons bordering the infarct area. After transient middle cerebral artery occlusion however, messenger RNA levels of protein inhibitor of neuronal nitric oxide synthase increased in the reperfused neocortex. Our findings indicate that cerebral ischemia leads to an increase in neuronal expression of protein inhibitor of neuronal nitric oxide synthase in brain regions where sustained or "uncoupled" nitric oxide synthase activity may be detrimental to neurons. Lack of post-ischemic induction of protein inhibitor of neuronal nitric oxide synthase in CA1 pyramidal neurons may result in high nitric oxide synthase activity after global ischemia and could contribute to delayed neuronal cell death.
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PMID:Induction of protein inhibitor of neuronal nitric oxide synthase/cytoplasmic dynein light chain following cerebral ischemia. 952 64

The purpose of this study was to determine whether nitric oxide (NO) is present in clinically normal horses under basal conditions and if it increases secondary to naturally acquired small intestinal strangulation obstruction. Thirty-one horses were used; 20 horses with naturally acquired small intestinal strangulation obstruction and 11 clinically normal horses with no signs of gastrointestinal tract disease. Jugular venous blood, abdominal fluid, and urine were collected for NO quantification. Plasma, abdominal fluid, and urine were stored at -70 degrees C until analyzed for NO using a chemiluminescent method. Biopsy specimens collected from the affected jejunal segment, during anesthesia or after immediately after euthanasia, or from the midjejunum of control horses, were divided into subsections for fixation in zinc formalin and cryopreservation in OCT gel. Nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) diaphorase histochemical stains were performed on cryopreserved tissues and inducible nitric oxide synthase (iNOS) and nitrotyrosine immunohistochemical stains were performed on formalin-fixed, paraffin-embedded tissues. There were significantly greater plasma and abdominal fluid NO concentrations in affected horses as compared with controls, but there were no significant differences between horses for urine NO concentrations. There was a significant decrease in NADPH diaphorase stain in mucosal epithelium, vasculature, and leukocytes, and in submucosal plexi in affected horses compared with control horses. There was a significant increase in iNOS staining in mucosal and submucosal leukocytes and in mucosal leukocyte nitrotyrosine staining of the affected compared with control horses. Endothelial NOS and neuronal NOS are present under basal conditions in the jejunum of horses and probably mediate physiologic or cytoprotective effects. Plasma and abdominal fluid, but not urine, NO concentrations increase subsequent to small intestinal strangulation obstruction; this may be associated with increased mucosal and submucosal iNOS staining in leukocytes, which was likely due to increased expression subsequent to stimuli associated with ischemia. The increased nitrotyrosine staining in mucosal leukocytes of affected horses likely reflects the presence of peroxynitrite subsequent to increased NO and superoxide production and may reflect a cytotoxic role of NO in small intestinal strangulation obstruction in horses.
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PMID:Detection and comparison of nitric oxide in clinically normal horses and those with naturally acquired small intestinal strangulation obstruction. 1053 1

An astrocyte antioxidant enzyme, quinone reductase (QR), was studied in vivo to assess whether its activity was up-regulated following cerebral ischemia. Rats were given a unilateral focal cerebral infarct and regions of interest within the ischemic penumbra compared to the non-ischemic side for QR activity. At 7 days post-ischemia, QR activity was significantly up-regulated within cells of astrocyte morphology in the cortex (p = 0.007) and subcortical (p = 0.005) areas adjacent to the infarct. This enzyme activity peaked at 7 days but was still significantly up-regulated at 14 days. Up-regulation of QR activity occurs within the ischemic penumbra of a stroke in this animal model and may contribute to factors that limit ischemic damage to neurons in this area.
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PMID:The antioxidant enzyme quinone reductase is up-regulated in vivo following cerebral ischemia. 1130 43

To investigate the sites of nitric oxide synthase (NOS) expression after brain injury, NADPH-d histochemistry was performed on the hypothalamo-neurohypophysial system (HNS) of adult rats several days after both ischemia and trauma. Electron-microscopic examination revealed the sites of formazan end-product of the diaphorase reaction in some neurons, astrocytes, cells and vascular pericytes, and in all activated microglial/macrophagal cells in perivascular and juxtaneuronal regions of hypothalamus. In neurohypophysis, positive NADPH-d staining was present in cytosol of many pituicytes, endothelial cells, pericytes and corresponding axonal endings. NADPH-d activity was also present in perivascular macrophages or microglial cells of neurohypophysis. Finally, we suppose that NOS expression and the consequent productions of nitric oxide could be involved in pathophysiology of HNS injury by ischemia and trauma, where activations inducible isoform of NOS especially, may contribute to a variety of neurogenerative processes. The imbalance in regulation of nitric oxide could disturb the physiological function of this neuroendocrine system.
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PMID:Expression of NADPH-diaphorase (NOS) in rat hypothalamo-neurohypophysial system after ischemic and traumatic brain injury. 1145 99

Ischemic preconditioning (IPC) may protect the liver from ischemia reperfusion injury by nitric oxide formation. This study has investigated the effect of ischemic preconditioning on hepatic microcirculation (HM), and the relationship between nitric oxide metabolism and HM in preconditioning. Rats were allocated to 5 groups: 1. sham laparotomy; 2. 45 minutes lobar ischemia followed by 2-hour reperfusion (IR); 3. IPC with 5 minutes ischemia and 10 minutes reperfusion before IR; 4. L-arginine before IR; and 5. L-NAME + IPC before IR. HM was monitored by laser Doppler flowmeter. Liver transaminases, adenosine triphosphate, nitrites + nitrates, and guanosine 3'5'-cyclic monophosphate (cGMP) were measured. Nitric oxide synthase (NOS) distribution was studied using nicotinamide adeninine dinucleotide phosphate (NADPH) diaphorase histochemistry. At the end of reperfusion phase, in the IR group, flow in the HM recovered partially to 25.8% of baseline (P < .05 versus sham), whereas IPC improved HM to 49.5% of baseline (P < .01 versus IR). With L-arginine treatment, HM was 31.6% of baseline (NS versus IR), showing no attenuation of liver injury. In the preconditioned group treated with L-NAME, HM declined to 10.2% of baseline, suggesting not only a blockade of the preconditioning effect, but also an exacerbated liver injury. Hepatocellular injury was reduced by IPC, and L-arginine and was increased by NO inhibition with L-NAME. IPC also increased nitrate + nitrate (NOx) and cGMP concentrations. NOS detected by NADPH diaphorase staining was associated with hepatocytes and vascular endothelium, and was induced by IPC. IPC induced NOS and attenuated HM impairment and hepatocellular injury. These data strongly suggest a role for nitric oxide in IPC.
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PMID:Effect of ischemic preconditioning on hepatic microcirculation and function in a rat model of ischemia reperfusion injury. 1247 59

The effects of acupuncture on the expressions of nitric oxide synthase (NOS) and c-Fos in the hippocampus of gerbils after transient ischemia were investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and Fos immunohistochemistry. In animals of the ischemia-induction groups, both common carotid arteries were occluded for 5 minutes. Animals of the acupunctued groups were given acupunctural treatment at Zusanli twice daily for 9 consecutive days. Acupuncture was shown to decrease NADPH-d and c-Fos levels in both the sham-operation group and the ischemia-induction group. These results suggest that acupuncture modulates the expressions of NOS and c-Fos in the hippocampus.
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PMID:Acupuncture modulates expressions of nitric oxide synthase and c-Fos in hippocampus after transient global ischemia in gerbils. 1458 81

Recent studies have shown that (-)-epigallocatechin gallate (EGCG), one of the green tea polyphenols, has a potent antioxidant property. Nitric oxide (NO) plays an important role in the neuropathogenesis induced by brain ischemia/reperfusion and hypoxia. This study aimed to explore the potential neuroprotective effect of EGCG on the ganglionic neurons of the nodose ganglion (NG) in acute hypoxic rats. Thus, the young adult rats were pretreated with EGCG (10, 25, or 50 mg/kg, i.p.) 30 min before they were exposed to the altitude chamber at 10,000 m with the partial pressure of oxygen set at the level of 0.27 atm (pO2=43 Torr) for 4 h. All the animals examined were allowed to survive for 3, 7, and 14 successive days, respectively, except for those animals sacrificed immediately following hypoxic exposure. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry were carried out to detect the neuronal NADPH-d/nNOS expression in the NG. The present results show a significant increase in the expression of NADPH-d/nNOS reactivity in neurons of the NG at various time intervals following hypoxia. However, the hypoxia-induced increase in NADPH-d/nNOS expression was significantly depressed only in the hypoxic rats treated with high dosages of EGCG (25 or 50 mg/kg). These data suggest that EGCG may attenuate the oxidative stress following acute hypoxia.
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PMID:Green tea polyphenol (-)-epigallocatechin gallate attenuates the neuronal NADPH-d/nNOS expression in the nodose ganglion of acute hypoxic rats. 1474 23

Cycling of intracellular pH has recently been shown to play a critical role in ischemia-reperfusion injury. Ischemia-reperfusion also leads to mitochondrial matrix acidification and dysfunction. However, the mechanism by which matrix acidification contributes to mitochondrial dysfunction, oxidative stress, and the resultant cellular injury has not been elucidated. We observe pH-dependent equilibria between monomeric, dimeric, and a previously undescribed tetrameric form of pig heart lipoamide dehydrogenase (LADH), a mitochondrial matrix enzyme. Dynamic light scattering studies of native LADH in aqueous solution indicate that lowering pH favors a shift in average molecular mass from higher oligomeric states to monomer. Sedimentation velocity of LADH entrapped in reverse micelles reveals dimer and tetramer at both pH 5.8 and 7.5, but monomer was observed only at pH 5.8. Enzyme activity measurements in reverse Aerosol OT micelles in octane indicate that LADH dimer and tetramer possess lipoamide dehydrogenase and diaphorase activities at pH 7.5. Upon acidification to pH 5.8 only the LADH monomer is active and only the diaphorase activity is observed. These results indicate a correlation between pH-dependent changes in the LADH reaction specificity and its oligomeric state. The acidification of mitochondrial matrix that occurs during ischemia-reperfusion injury is sufficient to alter the structure and enzymatic specificity of LADH, thereby reducing mitochondrial defenses, increasing oxidative stress, and slowing the recovery of energy metabolism. Matrix acidification may also disrupt the quaternary structure of other mitochondrial protein complexes critical for cellular homeostasis and survival.
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PMID:pH-dependent substrate preference of pig heart lipoamide dehydrogenase varies with oligomeric state: response to mitochondrial matrix acidification. 1571 Jun 13


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