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:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Previously, PAHX-AP1 (PAHX-associated protein 1) was isolated as a novel protein to interact with Refsum disease gene product (phytanoyl-CoA alpha-hydroxylase, PAHX) and specifically expressed in mouse brain. PAHX-AP1 is also suggested to be involved in the development of the central neurologic deficits of Refsum disease. To clarify its function, we have searched for proteins that associate with PAHX-AP1 via yeast two-hybrid system. We found that PAHX-AP1 interacts with the cytoplasmic region of human brain-specific angiogenesis inhibitor 1 (hBAI1), and isolated murine homolog of hBAI1. Structural analysis of the PAHX-AP1 with three reported hBAI-associated proteins (BAP) revealed no homology among them, and we designated PAHX-AP1 as BAP4. The ability of BAP4 to interact with BAI1 was confirmed by pulling-down BAI1 with GST-BAP4 protein and immunoprecipitation study using brain lysate. Northern and Western blot analyses demonstrated a unique pattern of BAI1 expression in the brain. The peak level of BAI1 was observed 10 days after birth. In situ hybridization analyses of the brain showed the same localization of BAI1 as BAP4, such as most neurons of cerebral cortex, hippocampus, and V, VI, VII, VIII, and XII nuclei. Because BAI1 possessed thrombospondin-type 1 repeats in its extracellular region, changes of BAI1 expression were examined in the focal cerebral ischemia model. The BAI1 expression decreased on the ischemic side after 24 h but BAP4 was not changed after the time-course of ischemia. Our results indicate that expression and localization of BAI1 in the brain is correlated with BAP4, and that BAI1 is involved in inhibition of angiogenesis and neuronal differentiation.
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PMID:Characterization of mouse brain-specific angiogenesis inhibitor 1 (BAI1) and phytanoyl-CoA alpha-hydroxylase-associated protein 1, a novel BAI1-binding protein. 1124 25

The effect of Khamira Abresham Uood Mastagiwala (KAUM) (a preparation of Indian System of Unani Medicine) on the activity of antioxidant enzymes, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and the content of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) was studied in the middle cerebral artery occluded (MCAO) rats after 15 days pretreatment (200 mg/kg body weight (b.wt.), orally) of Khamira Abresham Uood Mastagiwala. The rats were trained and assessed for neurobehavioral activity using Cook's climbing pole. The middle cerebral artery of adult male Wistar rats was occluded for 2 h and reperfused for 22 h. The activity of GPx, GST, GR, catalase and content of GSH was decreased significantly in MCAO group as compared with sham. The rats of MCAO + KAUM group have shown a significant protection in the activity of above-mentioned antioxidant enzymes and content of glutathione when compared with MCAO group. The significantly elevated level of TBARS in MCAO group was depleted significantly by the pretreatment of animals with KAUM in MCAO group. The neurobehavioral assessment has also strengthened the above biochemical data thereby indicating that the therapeutic intervention of KAUM, which is a potent cardiac and melancholic tonic, can be used to prevent or reduce the deterioration caused by free radicals thereby preventing subsequent pathological and biochemical changes which occur during cerebral ischemia.
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PMID:Protective effect of Khamira Abresham Uood Mastagiwala against free radical induced damage in focal cerebral ischemia. 1589 24

Active oxygen species alter the activities of the enzymes involved in the defence against free radicals and substantially influence the aging process and age-dependent neuropathology. Unilamellar liposomes were used to deliver flavonoidal antioxidant quercetin (QC) to rat brain. Antioxidant potential of QC loaded in mannosylated (QC 7.2 micromol/kg b.wt.) liposomes (50 nm) was investigated by an in vivo model of cerebral ischemia and reperfusion on Sprague Dawley young (2 months old, b.wt. 160-180 g) and aged (20 months old, b.wt. 415-440 g) rats. Animals were made ischemic for 30 min by bilateral clamping of the common carotid artery followed by a 30 min cerebral reperfusion by withdrawing the clamping. Diene level and (GSSG/GSH) ratio were found to be higher in normal aged, compared to normal young rat brain. Superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione S-transferase activities were lower in normal aged rat brain. Further reduction of these antioxidant enzymes was observed in aged rat brain by the induction of cerebral ischemia and reperfusion. Mannosylated liposomally encapsulated QC treatment resulted in a significant preservation of the activities of antioxidant enzymes and a marked inhibition of cellular edema formation in neuronal cells of young and old rats.
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PMID:Mannosylated liposomal flavonoid in combating age-related ischemia-reperfusion induced oxidative damage in rat brain. 1648 Jul 58

The modifying effects of Crocus sativus (CS) stigma extract on neurobehavioral activities, malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase (SOD), catalase (CAT), and Na(+),K(+)-ATPase activities, and glutamate (Glu) and aspartate (Asp) content were examined in the middle cerebral artery (MCA) occlusion (MCAO) model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 hours using intraluminal 4-0 monofilament, and reperfusion was allowed for 22 hours. MCAO caused significant depletion in the contents of GSH and its dependent enzymes while significant elevation of MDA, Glu, and Asp. The activities of Na(+),K(+)-ATPase, SOD, and CAT were decreased significantly by MCAO. The neurobehavioral activities (grip strength, spontaneous motor activity, and motor coordination) were also decreased significantly in the MCAO group. All the alterations induced by ischemia were significantly attenuated by pretreatment of CS (100 mg/kg of body weight, p.o.) 7 days before the induction of MCAO and correlated well with histopathology by decreasing the neuronal cell death following MCAO and reperfusion. The present results may suggest the effectiveness of CS in focal ischemia most probably by virtue of its antioxidant property.
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PMID:Effect of Saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats. 1682 11

The objective of the present study was to investigate the effects of aqueous garlic extract (AGE) on neurobehavioral activities, malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and sodium-potassium ATPase (Na(+),K(+)-ATPase) activities, and glutamate and aspartate content in a middle cerebral artery (MCA) occlusion (MCAO) model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 hours using intraluminal 4-0 monofilament, and reperfusion was allowed for 22 hours. MCAO caused significant depletion in GSH and its dependent enzymes (GPx, GR, and GST) and significant elevation of MDA, glutamate, and aspartate. The activities of Na(+),K(+)- ATPase, SOD, and CAT were decreased significantly by MCAO. The neurobehavioral activities (grip strength, spontaneous motor activity, and motor coordination) were also decreased significantly in the MCAO group. All of the alterations induced by ischemia were significantly attenuated by pretreatment with AGE (500 mg/mL/kg of body weight, i.p.) 30 minutes before the induction of MCAO and correlated well with histopathology by decreasing the neuronal cell death following MCAO and reperfusion. These findings suggest that AGE effectively modulates neurobehavioral and neurochemical changes in focal ischemia, most probably by virtue of its antioxidant properties.
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PMID:Behavioral and histologic neuroprotection of aqueous garlic extract after reversible focal cerebral ischemia. 1720 42

Majun Baladar (MB), a traditional herbal formulation of the Unani system of medicine, was studied for its efficacy against cerebral ischaemia-induced oxidative damage in hippocampus and associated neurobehavioural deficits. Adult male Wistar rats were divided into four groups. The first group was sham, the second group was ischaemic (MCAO: middle cerebral artery occluded) and the third group was a MB pre-treated ischaemic group (MCAO + MB). The fourth group was given MB (1.05 g/kg) orally for 15 days as a drug control. The middle cerebral artery was occluded for 2 hr and reperfused for 22 hr in the ischaemic as well as the drug pre-treated group. The activity of the various enzymatic antioxidants like glutathione peroxidase, glutathione reductase, glutathione S-transferase and non-enzymatic antioxidants, glutathione along with levels of lipid peroxidation were evaluated. Cerebral ischaemic rats showed elevated level of lipid peroxidation and decreased levels of various antioxidants significantly over sham values. As a result of MB pre-treatment, the level of lipid peroxidation was found to be significantly depleted as compared to the ischaemic group. Furthermore, depleted levels of glutathione and the activity of glutathione peroxidase, glutathione S-transferase and glutathione reductase were restored significantly in MB treated group. Majun Baladar exhibited a significant improvement in neurobehavioural activities in the drug pre-treated animals as compared to the ischaemic group as evidenced by the grip strength test, Rota-Rod and video path analysis. The results of the present study provide baseline information regarding the neuroprotective efficacy of MB and also open a window for a potent therapeutic use of this traditional herbal Unani medicine.
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PMID:Oral supplementation of Majun Baladar ameliorates antioxidant enzyme activities in cerebral ischaemic damage. 1784 6

Reactive oxygen species (ROS) is massively produced in the brain after cerebral ischemia and reperfusion. It reacts strongly with cellular components, which has detrimental effects and leads to neuronal cell death. DJ-1, which was found to be the causative gene of familial Parkinson's disease PARK7, is a multifunction protein, which plays a key role in transcriptional regulation, and a molecular chaperone. In this study, we investigated the neuroprotective effect of DJ-1 against neurodegeneration caused by ischemia/reperfusion injury. Cerebral ischemia was induced in rats by 120 mins of middle cerebral artery occlusion (MCAO) using an intraluminal introduction method. The intrastriatal injection of recombinant glutathione S-transferase-tagged human DJ-1 (GST-DJ-1) markedly reduced infarct size in 2,3,5-triphenyltetrazolium chloride staining at 3 days after MCAO. In addition, we performed a noninvasive evaluation of ischemic size using magnetic resonance imaging and found a significant reduction of infarct size with the administration of GST-DJ-1. In GST-DJ-1-treated rats, behavioral dysfunction and nitrotyrosine formation were significantly inhibited. Furthermore, GST-DJ-1 markedly inhibited H(2)O(2)-mediated ROS production in SH-SY5Y cells. These results indicate that GST-DJ-1 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that DJ-1 may be a useful therapeutic target for ischemic neurodegeneration.
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PMID:DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats. 1788 63

In dyscirculatory encephalopathy and moderate ischemic stroke there are single changes of components of glutathione metabolism. In moderate and severe ischemic stroke frequent and considerable changes have been revealed. Changes in hemorrhagic stroke are also expressed. An increase of activities of glutathione peroxidase and glutathione transferase is the most typical, rarely the increase of glutathione reductase and GSH is observed. The increase of enzymes activity was absent at the delayed oneset of treatment (more than 3 days) and in severe cases patients who died later. Glutathione system is important in the tolerance to cerebral ischemia.
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PMID:[Glutathione system in erythrocytes and blood plasma in strokes and dyscirculatory encephalopathy]. 1803 26

Astrocytes, one of the predominant types of glial cells, function as both supportive and metabolic cells for the brain. Under cerebral ischemia/reperfusion-induced oxidative conditions, astrocytes accumulate and activate in the ischemic region. DJ-1 has recently been shown to be a sensor of oxidative stress in living cells. However, the function of astrocytic DJ-1 is still unknown. In the present study, to clarify the effect of astrocytic DJ-1 protein under massive oxidative insult, we used a focal ischemic rat model that had been subjected to middle cerebral artery occlusion (MCAO) and reperfusion. We then investigated changes in the distribution of DJ-1 in astrocytes, DJ-1 release from cultured astrocytes, and the effects of recombinant DJ-1 protein on hydrogen peroxide (H(2)O(2))-induced death in normal and DJ-1-knockdown SH-SY5Y cells and on in vitro scavenging of hydroxyl radicals ((*)OH) by electron spin resonance spectrometry. At 24 h after 2-h MCAO and reperfusion, an infarct lesion was markedly observed using magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. In addition, reactive astrocytes enhanced DJ-1 expression in the penumbral zone of the ischemic core and that DJ-1 protein was extracellularly released from astrocytes by H2O2 in in vitro primary cultures. Although DJ-1-knockdown SH-SY5Y cells were markedly vulnerable to oxidative stress, treatment with glutathione S-transferase-tagged recombinant human DJ-1 protein (GST-DJ-1) significantly inhibited H(2)O(2)-induced cell death. In addition, GST-DJ-1 protein directly scavenged (*)OH. These results suggest that oxidative stress induces the release of astrocytic DJ-1 protein, which may contribute to astrocyte-mediated neuroprotection.
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PMID:Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury. 2004 43


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