Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copper-zinc-superoxide dismutase (CuZn-SOD), a cytosolic antioxidant enzyme that is specific for scavenging superoxide radicals, is involved in neuroprotective mechanisms in brain injury following trauma and cerebral ischemia. Liposome-entrapped CuZn-SOD exhibit beneficial effects in vivo on cold-induced vasogenic edema and on blood-brain barrier disruption. The increased levels of edema and infarction following a focal cerebral ischemia also are decreased by the pretreatment of liposome-entrapped CuZn-SOD. The protective role of SOD on brain injury was further extended and confirmed in studies using transgenic mice overexpressing human CuZn-SOD. Our studies so far suggest that increased cerebral levels of SOD, either by means of external pharmacological application or by genetic manipulations, ameliorate brain edema and infarction induced by trauma and focal cerebral ischemia.
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PMID:Antioxidant-dependent amelioration of brain injury: role of CuZn-superoxide dismutase. 131 99

Using a mouse model with intraluminal blockade of the middle cerebral artery (MCA) which produced both cortical and striatal infarction, the effect that superoxide radicals have on cerebral infarction, local cerebral blood flow, and neurological deficits after 24 h of permanent focal cerebral ischemia in transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) was examined. There were no difference between SOD-1 Tg mice and non-Tg littermates observed in the infarct areas of brain slices, the infarct volume, the local cerebral blood flow, or the neurological deficits. These data suggest that pre-existing high levels of antioxidant enzyme failed to provide neuronal protection against permanent focal cerebral ischemia.
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PMID:Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal cerebral ischemia. 829 91

Superoxide dismutase is well known to act as an effective antioxidant enzyme against cellular damage caused by oxidative stresses including ischemia/reperfusion-induced cerebral injury. However, it is still controversial whether or not the activity of endogenous superoxide dismutase changes during cerebral ischemia and reperfusion. In order to elucidate this phenomenon, we assayed the superoxide dismutase activity in the cerebral tissues of gerbils using the chemiluminescence method with a Cypridina luciferin analog. This method was demonstrated to be a sensitive and specific assay for the enzymatic activity of superoxide dismutase in cerebral tissues, which was not subject to interference from proteins or ascorbate. After 3 h of focal and global ischemia, there were no changes in the cerebral tissue superoxide dismutase activities. After 24 h of reperfusion following 1 h of ischemia, the superoxide dismutase activity decreased only approx 20%, whereas the adenylate kinase activities, measured in the same cerebral tissues as those used for superoxide dismutase assay, started to decline 1 h after reperfusion commenced and were approx 50% of the control levels after 24 h. These results show that almost all the activity of endogenous superoxide dismutase is maintained and does not decrease significantly as a result of ischemia/reperfusion-induced cerebral injury.
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PMID:The superoxide dismutase activities of cerebral tissues, assayed by the chemiluminescence method, in the gerbil focal ischemia/reperfusion and global ischemia models. 836 36

Brain injury, as occurs in stroke or head trauma, induces a dramatic increase in levels of tumor necrosis factor-alpha (TNF), but its role in brain injury response is unknown. We generated mice genetically deficient in TNF receptors (TNFR-KO) to determine the role of TNF in brain cell injury responses. Damage to neurons caused by focal cerebral ischemia and epileptic seizures was exacerbated in TNFR-KO mice, indicating that TNF serves a neuroprotective function. Oxidative stress was increased and levels of an antioxidant enzyme reduced in brain cells of TNFR-KO mice, indicating that TNF protects neurons by stimulating antioxidant pathways. Injury-induced microglial activation was suppressed in TNFR-KO mice, demonstrating a key role for TNF in injury-induced immune response. Drugs that target TNF signaling pathways may prove beneficial in treating stroke and traumatic brain injury.
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PMID:Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. 867 25

Much evidence exists in support of the hypothesis that free radicals contribute to the pathogenesis of several neurodegenerative disorders and that mechanisms of free radical generation occur both intracellularly and extracellularly. Previous studies in this laboratory have shown that covalent modification of growth factors and antioxidant enzymes with the naturally occurring polyamine, putrescine, increases their permeability at the blood-nerve and blood-brain barriers (BNB and BBB), but does not significantly inhibit bioactivity. Furthermore, putrescine-modified superoxide dismutase (SOD) was shown to reduce neurodegeneration in a rat model of global cerebral ischemia. The purpose of the present study was to modify the antioxidant enzyme, catalase (CAT), with putrescine (PUT) at carboxylic acid groups whose ionization, and hence reactivity, was controlled with pH and investigate the effects on permeability and enzymatic activity. Modification of CAT with PUT increased its permeability 2-3-fold and preserved 67% of its enzymatic activity compared to native CAT and 137% compared to lyophilized CAT. The results of this study indicate that modification of CAT with putrescine increases its permeability while preserving enzymatic activity. PUT-SOD administered in combination with PUT-CAT may eliminate both the superoxide radical and the H2O2 produced from the dismutation of superoxide, respectively, and thus prevent the formation of hydroxyl radicals. This combination may exhibit increased neuroprotective effects, compared to native enzymes, following systemic administration for the treatment of free radical associated neurodegenerative disorders.
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PMID:Putrescine-modified catalase with preserved enzymatic activity exhibits increased permeability at the blood-nerve and blood-brain barriers. 936 24

Both acidosis and oxidative stress contribute to ischemic brain injury. The present study examines interactions between acidosis and oxidative stress in murine cortical cultures. Acidosis (pH 6.2) was found to potentiate markedly neuronal death induced by H2O2 exposure. To determine if this effect was mediated by decreased antioxidant capacity at low pH, the activities of several antioxidant enzymes were measured. Acidosis was found to reduce the activities of glutathione peroxidase and glutathione S-transferase by 50-60% (p < 0.001) and the activity of glutathione reductase by 20% (p < 0.01) in lysates of the cortical cultures. Like acidosis, direct inhibition of glutathione peroxidase with mercaptosuccinate also potentiated H2O2 toxicity. Because acidosis may accelerate hydroxyl radical production by the Fenton reaction, the effect of iron chelators was also examined. Both desferrioxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, two structurally different iron chelators, significantly reduced H2O2-induced neuronal death under both pH 7.2 and pH 6.2 conditions. These results suggest that the increased cell death produced by severe acidosis during cerebral ischemia may result in part from exacerbation of oxidative injury. This exacerbation may result from both impaired antioxidant enzyme functions and increased intracellular free iron levels.
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PMID:Acidosis potentiates oxidative neuronal death by multiple mechanisms. 1050 Dec

Whether naloxone may modulate energy metabolism and endogenous antioxidant enzyme activities in ischemic cortex was studied. Cerebral ischemia/reperfusion (I/R) was produced by occluding two common carotid arteries and the right middle cerebral artery for 90 min followed by reperfusion in anesthetized Sprague-Dawley rats. Both pre-treatment (0.03 or 0.3 mg) and post-treatment (0.3 mg) of naloxone by intracerebroventricular infusion significantly reduced cortical infarct volumes. Pre-treatment with 0.03 mg reduced ischemia-induced suppression of extracellular pyruvate level and enhancement of lactate/pyruvate ratio as well as cerebral I/R-induced increases of endogenous catalase, glutathione peroxidase, and manganese superoxide dismutase activities. In conclusion, neuroprotective effects of naloxone in terms of reducing brain infarction involve attenuation of the disturbance of cellular functions following cerebral I/R via restoration of mitochondrial activities or energy metabolism.
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PMID:Effects of naloxone on lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/reperfusion. 1085 25

Time-dependent changes in the activities of antioxidant enzymes and an oxidant enzyme, xanthine oxidase (XO), were detected in primary and peri-ischaemic brain regions during permanent occlusion of the middle cerebral artery (MCAO) in rats. There were no changes in superoxide dismutase (SOD) and catalase (CAT) activities after 3 h of MCAO, whereas antioxidant enzyme activities decreased significantly in ischaemic brain areas following 24 h of ischaemia. After 48 h, the enzyme activities returned to the baseline but then a further increase was observed in ischaemic brain areas by 72 h post-ischaemia. Normally, XO exists as a dehydrogenase (XD), but it is converted to XO which contributes to injury in some ischaemic tissues. The XO activity increased slightly at 3 h after ischaemia, but after 24 h of ischaemia it returned to the baseline and then remained relatively unchanged in ischaemic areas. Pretreatment with allopurinol before ischaemia prevented changes in SOD and CAT activities and attenuated brain oedema during 24 h of ischaemia. Neither XO nor XD activity changed in allopurinol-treated rats at the times of ischaemia. These results indicated that ischaemic brain tissue remained vulnerable to free radical damage for as long as 48 h after ischaemia, and XO was probably not an important source of free radicals in cerebral ischaemia.
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PMID:Time-dependent changes in superoxide dismutase, catalase, xanthine dehydrogenase and oxidase activities in focal cerebral ischaemia. 1096 80

Numerous studies indicate a role for oxidative stress in the neuronal degeneration and cell death that occur during ischemia-reperfusion injury. Recent data suggest that inhibition of the proteasome may be a means by which oxidative stress mediates neuronal cell death. In the current study, the authors demonstrate that there is a time-dependent decrease in proteasome activity, which is not associated with decreased expression of proteasome subunits, after cerebral ischemia-reperfusion injury. To determine the role of oxidative stress in mediating proteasome inhibition, ischemia-reperfusion studies were conducted in mice that either overexpressed the antioxidant enzyme glutathione peroxidase [GPX 1(+)], or were devoid of glutathione peroxidase activity (GPX -/-). After ischemia-reperfusion, GPX 1(+) mice displayed decreased infarct size, attenuated neurologic impairment, and reduced levels of proteasome inhibition compared with either GPX -/- or wild type mice. In addition, GPX 1(+) mice displayed lower levels of 4-hydroxynonenal-modified proteasome subunits after ischemia-reperfusion injury. Together, these data indicate that proteasome inhibition occurs during cerebral ischemia-reperfusion injury and is mediated, at least in part, by oxidative stress.
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PMID:Oxidative stress-associated impairment of proteasome activity during ischemia-reperfusion injury. 1104 9

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


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