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 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

Renal function in the early post-transplantation period depends largely on factors affecting the kidney prior to implantation. Function of the graft may be also disturbed by the most common complications of the early post-operative period such as acute graft rejection (AGR), acute tubular necrosis (ATN) and may be modified by nephrotoxic action of cyclosporine A (CsA). Evaluation of excretion of enzymes and low molecular weight proteins (LMWP) may help in the differentiation of these complications. Aim Comparison of the urinary excretion of markers of tubular injury in patients with AGR, ATN, or patients with stable graft function (SGF) was made and differences between groups and correlations between markers and cold ischemia time (CIT), warm ischemia time (WIT) and blood trough level of cyclosporine A (CsA0) were determined. Material and methods In 60 cadaveric renal allograft recipients in the early post-transplantation period urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and B isoenzyme (NAG-B), alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), alpha and pi isoenzymes of glutathione S-transferase (alpha-GST, pi-GST), retinol binding protein (RBP) and beta2- microglobulin (beta2M), were analyzed. Results NAG and NAB-B activities were higher in ATN (P<0.05, P<0.01) and in AGR (P<0.005, P<0.02) than in SGF. Excretion of pi-GST was higher in AGR than in SGF (P<0.0002) or ATN (P<0.007). CIT and WIT in patients with ATN were higher (P<0.05) than in SGF group. In ATN patients, correlations of CIT with RBP (P<0.05) and pi-GST (P<0.05), and WIT with RBP (P<0.05), and pi-GST (P<0.001) were found. Conclusions High urinary NAG and NAG B excretion characterizes ATN and AGR patients. Evaluating urinary excretion of pi-GST may be helpful in differentiating AGR from ATN. However, taking into account ischemia time is necessary in interpreting the pi-GST value in early post transplant period.
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PMID:Enzymuria and low molecular weight protein excretion as the differentiating marker of complications in the early post kidney transplantation period. 1716 Apr 49

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

Reactive oxygen species (ROS)-induced injury has been shown to occur during the reperfusion phase of ischemia-reperfusion and ROS are known to induce signaling events. We hypothesized that oxygen sensing in endothelial cells is also dependent on internal redox changes during hypoxia and that endothelial cells respond to changing oxygen environments via signaling, switching to an inflammatory phenotype. Endothelial cells exposed to relative hypoxia or the mitochondrial inhibitors rotenone, antimycin A, or FCCP show loss of mitochondrial membrane potential. During hypoxia, an increase in cytoplasmic ROS and glutathione S-transferase activity occurred, suggesting changes in intracellular redox state, mimicked with rotenone or FCCP but inhibited by antimycin A. Phosphorylation of stress-responsive mitogen-activated protein kinases occurred in hypoxia and was rapid and prolonged. Phosphorylation was inhibited by vitamin C, N-acetyl cysteine, or antimycin A. Chelation of intracellular calcium inhibits phosphorylation but the mitochondrial transition pore inhibitor cyclosporin A had no effect. Reoxygenation caused a further round of signaling, which was rapid but transient. Functionally, adhesion of neutrophils after hypoxia-reoxygenation under flow is ROS, P-selectin, and MAPK dependent. Therefore, changes in cellular signaling and phenotype are abrogated by ROS scavengers and suggest their use as therapeutic agents in ischemia-reperfusion.
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PMID:ROS generation in endothelial hypoxia and reoxygenation stimulates MAP kinase signaling and kinase-dependent neutrophil recruitment. 1738 98

Leukotriene (LT) C4 (LTC4) synthesis enzymes including LTC4 synthase (LTC4S), microsomal glutathione S-transferase (MGST) 2 and MGST3 can all conjugate LTA4 and reduced glutathione (GSH) to form LTC4, which is related to hepatic ischemia/reperfusion (I/R) injury. The relationship between nitric oxide (NO) and cysteinyl LTs has been shown in previous studies. However, the mechanisms of NO action on gene expression of LTC4 synthesis enzymes are still largely unclear during hepatic I/R. Adult male Sprague-Dawley rats were divided into 5 groups: a sham group (control), an I/R group, and sodium nitroprusside (SNP, 2.5, 5 and 10 microg/kg/min)+I/R groups. Livers were subjected to 60 min of partial hepatic ischemia followed by 5 h of reperfusion, saline or SNP (2.5, 5 and 10 microg/kg/min) administered intravenously. The mRNA levels of LTC4 synthesis enzymes, inducible NO synthase (iNOS) and endothelial No synthase (eNOS) in rat liver tissue were examined by RT-PCR; the protein expressions of NF-kappaB p65, p50 and IkappaBalpha in liver cell lysates and nuclear extracts were detected by Western blot analysis, and serum NO2. levels were also evaluated. Serum NO2. levels, the protein expressions of NF-kappaB p65 and p50 in the nucleus extract, and hepatic mRNA expressions of LTC4S and iNOS were decreased while hepatic mRNA of eNOS was increased in the SNP (5 and 10 microg/kg/min)+I/R groups when compared with those in the I/R group. SNP (2.5 microg/kg/min) promoted the mRNA expressions of both MGST2 and MGST3, whereas SNP (10 microg/kg/min) increased MGST2 mRNA but decreased MGST3 mRNA compared to those in I/R group. Compared with control, the mRNA expression of MGST2 and MGST3 were elevated in SNP (2.5 microg/kg/min)+I/R group, MGST3 mRNA was significantly declined in the SNP (5 and 10 microg/kg/min)+I/R groups. Immunohistochemistry staining revealed that I/R liver exhibited strong cytoplasmic and nuclear staining for NF-kappaB p65, but the livers of the SNP (2.5 microg/kg/min)+I/R group presented slight cytoplasmic and nuclear staining. But IkappaBalpha protein in all groups remains unchanged. It was concluded that SNP downregulated LTC4S mRNA expression by inhibiting NF-kappaB activation independent of IkappaBalpha, but appeared to have a dual influence on the mRNA expressions of MGST2 and MGST3 by other signaling pathways during hepatic I/R injury.
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PMID:Sodium nitroprusside regulates mRNA expressions of LTC4 synthesis enzymes in hepatic ischemia/reperfusion injury rats via NF-kappaB signaling pathway. 1749 35

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

The type 2 chloride intracellular channel, CLIC-2, is a member of the glutathione S-transferase structural family and a suppressor of cardiac ryanodine receptor (RyR2) Ca2+ channels located in the membrane of the sarcoplasmic reticulum (SR). Modulators of RyR2 activity can alter cardiac contraction. Since both CLIC-2 and RyR2 are modified by redox reactions, we speculated that the action of CLIC-2 on RyR2 may depend on redox potential. We used a GSH:GSSG buffer system to produce mild changes in redox potential to influence redox sensors in RyR2 and CLIC-2. RyR2 activity was modified only when both luminal and cytoplasmic solutions contained the GSH:GSSG buffer and the effects were reversed by removing the buffer from one of the solutions. Channel activity increased with an oxidizing redox potential and decreased when the potential was more reducing. Addition of cytoplasmic CLIC-2 inhibited RyR2 with oxidizing redox potentials, but activated RyR2 under reducing conditions. The results suggested that both RyR2 and CLIC-2 contain redox sensors. Since cardiac ischemia involves a destructive Ca2+ overload that is partly due to oxidation-induced increase in RyR2 activity, we speculate that the properties of CLIC-2 place it in an ideal position to limit ischemia-induced cellular damage in cardiac muscle.
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PMID:Redox potential and the response of cardiac ryanodine receptors to CLIC-2, a member of the glutathione S-transferase structural family. 1852 93

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a role in regulating a myriad of biological processes in virtually all brain cell types, including neurons. We and others have reported recently that drugs which activate PPARgamma are effective in reducing damage to brain in distinct models of brain disease, including ischemia. However, the cell type responsible for PPARgamma-mediated protection has not been established. In response to ischemia, PPARgamma gene is robustly upregulated in neurons, suggesting that neuronal PPARgamma may be a primary target for PPARgamma-agonist-mediated neuroprotection. To understand the contribution of neuronal PPARgamma to ischemic injury, we generated conditional neuron-specific PPARgamma knock-out mice (N-PPARgamma-KO). These mice are viable and appeared to be normal with respect to their gross behavior and brain anatomy. However, neuronal PPARgamma deficiency caused these mice to experience significantly more brain damage and oxidative stress in response to middle cerebral artery occlusion. The primary cortical neurons harvested from N-PPARgamma-KO mice, but not astroglia, exposed to ischemia in vitro demonstrated more damage and a reduced expression of numerous key gene products that could explain increased vulnerability, including SOD1 (superoxide dismutase 1), catalase, glutathione S-transferase, uncoupling protein-1, or transcription factor liver X receptor-alpha. Also, PPARgamma agonist-based neuroprotective effect was lost in neurons from N-PPARgamma neurons. Therefore, we conclude that PPARgamma in neurons play an essential protective function and that PPARgamma agonists may have utility in neuronal self-defense, in addition to their well established anti-inflammatory effect.
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PMID:Neuronal PPARgamma deficiency increases susceptibility to brain damage after cerebral ischemia. 1943 96

The benefits of ischemic preconditioning (IPC) in reducing ischemia/reperfusion injury (IRI) remain indistinct in human liver transplantation (LT). To further understand mechanistic aspects of IPC, we performed microarray analyses as a nested substudy in a randomized trial of 10-minute IPC in 101 deceased donor LTs. Liver biopsies were performed after cold storage and at 90 minutes postreperfusion in 40 of 101 subjects. Global gene expression profiles in 6 biopsy pairs in IPC and work standard organ recovery groups at both time points were compared using the Affymetrix GeneChip Human Gene 1.0 ST array. Transcripts with >1.5-fold change and P < 0.05 were considered significant. IPC altered expression of 82 transcripts in antioxidant, immunological, lipid biosynthesis, cell development and growth, and other groups. Real-time polymerase chain reaction and immunoblotting validated our microarray data. IPC-induced overexpression of glutathione S-transferase mu transcripts (GSTM1, GSTM3, GSTM4, and GSTM5) was accompanied by increased protein expression and may contribute to a decrease in oxidative stress. However, the increased expression of fatty acid synthase may increase oxidative stress, and tumor necrosis factor ligand superfamily member 10 may promote apoptosis. These changes, in combination with decreased expression of heparin-binding epidermal growth factor-like growth factor and insulin-like growth factor binding protein-1, both of which inhibit apoptosis, may increase IRI. In our study of deceased donor LT, IPC induces changes in gene expression, some of which are potentially beneficial but some which are potentially injurious. Thus, our findings of changes in gene expression mirror the outcomes in our clinical trial.
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PMID:Global gene expression profiles of ischemic preconditioning in deceased donor liver transplantation. 2044 Jul 68

Aldose reductase (AR) is a multifunctional enzyme that catalyzes the reduction of glucose and lipid peroxidation-derived aldehydes. During myocardial ischemia, the activity of AR is increased due to the oxidation of its cysteine residues to sulfenic acids. It is not known, however, whether the activated, sulfenic form of the protein (AR-SOH) is converted back to its reduced, unactivated state (AR-SH). We report here that in perfused mouse hearts activation of AR during 15 min of global ischemia is completely reversed by 30 min of reperfusion. During reperfusion, AR-SOH was converted to a mixed disulfide (AR-SSG). Deactivation of AR and the appearance of AR-SSG during reperfusion were delayed in hearts of mice lacking glutathione S-transferase P (GSTP). In vitro, GSTP accelerated glutathiolation and inactivation of AR-SOH. Reduction of AR-SSG to AR-SH was facilitated by glutaredoxin (GRX). Ischemic activation of AR was increased in GRX-null hearts but was attenuated in the hearts of cardiospecific GRX transgenic mice. Incubation of AR-SSG with GRX led to the regeneration of the reduced form of the enzyme. In ischemic cardiospecific AR transgenic hearts, AR was co-immunoprecipitated with GSTP, whereas in reperfused hearts, the association of AR with GRX was increased. These findings suggest that upon reperfusion of the ischemic heart AR-SOH is converted to AR-SSG via GSTP-assisted glutathiolation. AR-SSG is then reduced by GRX to AR-SH. Sequential catalysis by GSTP and GRX may be a general redox switching mechanism that regulates the reduction of protein sulfenic acids to cysteines.
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PMID:Postischemic deactivation of cardiac aldose reductase: role of glutathione S-transferase P and glutaredoxin in regeneration of reduced thiols from sulfenic acids. 2053 86


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