Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Utilization of highly enriched preparations of steroidogenic Leydig cells have proven invaluable for studying the direct effects of various hormones and agents on Leydig cell function in vitro. However, recent work indicates that isolated Leydig cells are often subjected to oxygen (O2) toxicity when cultured at ambient (19%) oxygen concentrations. Because intracellular antioxidants play an important role in protecting cells against oxygen toxicity, we have investigated the intracellular antioxidant defense system of isolated Leydig cells. The cellular levels of several antioxidants including catalase, glucose-6-phosphate dehydrogenase (G-6-PDH), superoxide dismutase (SOD) of the Cu/Zn & Mn variety, glutathione peroxidase, glutathione reductase and total glutathione were quantitated using enriched populations of Leydig cells isolated from adult male guinea pig testes. Compared to whole testicular homogenates, Leydig cells contained significantly (P < 0.01) less G-6-PDH, total SOD, glutathione reductase and total glutathione, but significantly (P < 0.001) more glutathione peroxidase. Compared to hepatic values previously reported in the guinea pig, Leydig cells contain nearly 400 times less catalase, about 14 times less glutathione peroxidase and almost 11 times less glutathione reductase. Since G-6-PDH and glutathione reductase are both necessary to regenerate reduced glutathione (GSH) which couples with glutathione peroxidase to breakdown hydrogen peroxide (H2O2) under normal conditions, it is plausible that the oxygen toxicity observed in isolated Leydig cells is due to the intracellular accumulation of H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1993 Sep 08
PMID:The antioxidant defense system of isolated guinea pig Leydig cells. 810 85

Exposure to a sublethal dose of endotoxin offers protection against subsequent oxidative stresses. The cellular mechanisms involved in generating this effect are not well understood. We evaluated the effect of endotoxin on antioxidant enzymes in liver peroxisomes. Peroxisomes have recently been shown to contain superoxide dismutase (SOD) and glutathione peroxidase (GPX) in addition to catalase. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment increased the specific activity of SOD and GPX in peroxisomes to 208% and 175% of control activity, respectively. These findings correlated with increases in peroxisomal SOD and GPX proteins observed by immunoblot. Although the quantity of catalase protein was increased when assessed by immunoblot analysis, the specific activity of catalase was decreased to 68% of control activity. Activation of catalase with ethanol only restored catalase activity to control levels suggesting that catalase had undergone irreversible inactivation. The observed increase in GPX activity may represent a compensatory mechanism triggered by accumulating H2O2. The data presented here suggest for the first time that mammalian peroxisomal antioxidant enzymes are altered during the oxidative injury of endotoxin treatment.
Mol Cell Biochem 1993 Sep 08
PMID:Peroxisomal participation in the cellular response to the oxidative stress of endotoxin. 810 87

We have investigated factors that regulate hydrogen peroxide (H2O2) release from vascular endothelial cells. Endothelial cells produce H2O2 at an intracellular site in the vicinity of peroxisomes and at a second site near the cell surface that is inaccessible to intracellular catalase or glutathione peroxidase. Regulation of H2O2 generation at the intracellular site was studied using aminotriazole, which inactivates catalase in the presence of H2O2. Regulation of H2O2 generation at the second site was studied by measuring H2O2 release into the medium. The rate of H2O2 release was constant over 2 h when cells were incubated in room air. Changing O2 levels in the atmosphere from 0% to 10% O2 resulted in a threefold increase in the rate of H2O2 release. Elevation of O2 levels from 10% to 95% O2 produced no further enhancement in the rate of release. Preincubation of cells under hypoxic conditions did not lead to an exaggerated rate of H2O2 release when cells were returned to room air. Pretreatment of cells with exogenous H2O2 inhibited subsequent H2O2 release while pretreatment with catalase enhanced H2O2 release. Although arachidonic acid transiently enhanced the rate of H2O2 release through a mechanism dependent on PGH synthase, basal H2O2 release was independent of this enzyme. Neither hypoxia, hyperoxia, or hypoxia followed by reoxygenation altered H2O2 generation at the intracellular site accessible to peroxisomal catalase. These data demonstrate that H2O2 release from endothelial cells is responsive to changes in O2 concentrations over a narrow range. The mechanisms involved are subject to product inhibition and appear to be saturated at 10% O2 in the atmosphere.
Am J Respir Cell Mol Biol 1993 Dec
PMID:Modulation of hydrogen peroxide release from vascular endothelial cells by oxygen. 825 92

cDNA clones encoding a 28-kDa subunit glutathione S-transferase (GST) from Schistosoma mansoni (Sm28GST) and a 26-kDa subunit GST from Schistosoma japonicum (Sj26GST) have been expressed in bacterial systems. The recombinant proteins were purified to homogeneity by batch-wash glutathione-agarose affinity chromatography and their biochemical properties investigated. Gel filtration chromatography indicated that both recombinant GSTs are homodimeric proteins. Resolution of Sm28GST and Sj26GST by chromatofocusing in the ranges pH 9-6 and pH 7-4 gave pI estimates of 7.4 and 5.0, respectively. Kinetic analyses suggested that both Sm28GST and Sj26GST operate via a sequential bisubstrate catalytic mechanism. Sm28GST and Sj26GST displayed a mosaic of mammalian Alpha-, Mu- and Pi-type substrate specificities and inhibitor sensitivities. However, multivariate analysis suggests that Sm28GST has an overall catalytic homology with mammalian Mu class GSTs, whilst the enzymatic properties of Sj26GST appear to constitute a hybridisation of Mu and Alpha class features. Both recombinant GSTs interact with a range of hydrophobic ligands including haematin and related compounds, bile acids and several anthelmintics. Sm28GST and Sj26GST possess relatively limited selenium-independent glutathione peroxidase activities, but are able to catalyse the glutathione conjugation of members of the trans,trans-alka-2,4-dienal, trans-alk-2-enal and 4-hydroxyalk-2-enal series of reactive carbonyls (known secondary products of lipid peroxidation).
Mol Biochem Parasitol 1993 Oct
PMID:Biochemical properties of cloned glutathione S-transferases from Schistosoma mansoni and Schistosoma japonicum. 826 29

The effect of ischemia-reperfusion on activity, protein and m-RNA levels of catalase, copper-zinc and manganese containing superoxide dismutases and glutathione peroxidase, the enzymes that are involved in free radical detoxification was studied in rat kidney. Ischemia alone did not alter either the activities or protein levels of superoxide dismutase and glutathione peroxidase. However, catalase activity was found to be inhibited to 82% of control. The inhibition of catalase was due to the inactivation of the enzyme as there was no significant change in enzyme protein level. Reperfusion following ischemia, however, led to a significant decrease in both the activities as well as the protein levels of all the antioxidant enzymes. The observed overall decrease in total superoxide dismutase activity was the net effect of a decrease in copper-zinc superoxide dismutase while manganese superoxide dismutase activity was found to be increased following reperfusion. This observed increase manganese superoxide dismutase activity was the result of its increased protein level. The mRNA levels for catalase, superoxide dismutases, and glutathione peroxidase were observed to be increased (100-145% of controls) following ischemia; reperfusion of ischemic kidneys, however, resulted in a significant decrease in the levels of mRNAs coding for all the enzymes except manganese superoxide dismutase which remained high. These results suggest that in tissue, the down regulation of the antioxidant enzyme system could be responsible for the pathophysiology of ischemia-reperfusion injury.
Mol Cell Biochem 1993 Aug 25
PMID:Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. 828 74

Difference between a novel monomeric enzyme and the classic tetrameric enzyme of glutathione peroxidase in rat liver was examined immunologically. The polyclonal antibody raised against the novel enzyme reacted with the novel enzyme, but not with the classic enzyme. Likewise the anti-classic enzyme antibody reacted with the classic enzyme, but not with the novel one. The activity of the novel enzyme was decreased by the treatment with the anti-novel enzyme antibody, but not with the anti-classic enzyme antibody, and vice versa for the classic enzyme. Thus the novel monomeric glutathione peroxidase is a protein immunologically distinct from the classic enzyme.
Biochem Mol Biol Int 1993 Apr
PMID:Immunological differentiation between novel monomeric and classic tetrameric rat liver glutathione peroxidases. 833 20

Oxidative stress may play an important role in the carcinogenic action of UVB light (290 to 320 nm). UVB light induces the growth-related immediate-early gene c-fos in JB6 mouse epidermal cells, but at the same time it causes structural damage to DNA, in particular DNA strand breakage. We have studied the effect of the modulation of the frequencies of DNA breaks on the transcriptional induction of c-fos by changing the cellular antioxidant defense or by inhibiting break repair. Reduction of UVB-induced DNA breakage in a stable transfectant with an increased complement of glutathione peroxidase enhanced the induction of c-fos. In contrast, c-fos induction was diminished in stable transfectants with Cu,Zn-superoxide dismutase. Increasing the stationary concentration of UVB-induced DNA breaks by inhibition of repair in the presence of the adenosine diphosphoribose (ADPR)-transferase inhibitor 3-amino-benzamide suppressed the induction of c-fos. We conclude that DNA breaks which are induced by UVB via oxidative processes interfere with the transcriptional induction of c-fos. DNA breaks appear to exert a long-range effect on chromatin conformation which is incompatible with efficient transcription. This notion is supported by the observation that inhibition of break rejoining by 3-amino-benzamide suppressed the UVB induction of the endogenous c-fos gene and of a stably integrated construct containing the c-fos regulatory sequences linked to a reporter gene. In contrast, the induction of the same construct was not inhibited when it remained extrachromosomal in transient transfection experiments.
Mol Cell Biol 1993 Nov
PMID:UVB-induced DNA breaks interfere with transcriptional induction of c-fos. 841 89

Time-dependent changes in levels of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPOD), and catalase (CAT) after cortical focal ischemia in rat indicate that: (1) primary and peri-ischemic tissues differ in both rate and the magnitude of oxyradical-induced ischemic injury, and (2) ischemic tissue remains vulnerable to oxyradical damage as long as 72 h after ischemia since the antioxidant enzyme levels remain at or below basal levels. After 72 h, the increased levels of these enzymes are sufficient to protect tissue against oxyradical damage. GM1 ganglioside (10 mg/kg, im) further increased the already elevated levels of the enzymes after ischemia, thereby indicating the GM1 treatment increases the capacity of ischemic tissue to protect against oxyradical injury.
Mol Chem Neuropathol
PMID:Temporal changes in superoxide dismutase, glutathione peroxidase, and catalase levels in primary and peri-ischemic tissue. Monosialoganglioside (GM1) treatment effects. 846 85

A gene encoding for a citrus salt-stress-associated protein (Cit-SAP) was cloned from Citrus sinensis salt-treated cell suspension. The gene, designated csa, was isolated from a cDNA expression library. The partial amino acid sequence of the protein, as well as that deduced from the nucleotide sequence of csa, revealed a considerable homology to mammalian glutathione peroxidase (GP), and to clone 6P229 from tobacco protoplasts. The increased expression of Cit-SAP in NaCl-treated cultured citrus cells and in citrus plants irrigated with saline water, and its similarity to GP, raise the possibility that one of the effects of salt stress in plants may be the increase of the level of free radicals.
Plant Mol Biol 1993 Mar
PMID:Molecular characterization of salt-stress-associated protein in citrus: protein and cDNA sequence homology to mammalian glutathione peroxidases. 846 85

Genomic clones containing the gene for the glutathione peroxidase-like androgen-regulated murine epididymal protein of 24 kilodaltons (arMEP24) were isolated. A 9-kilobase DNA fragment was sequenced and found to contain the entire coding region of the gene, which is divided into five exons. The exact sizes and boundaries of the exon blocks were deduced by comparison with the cDNA sequence. One major and four weak transcription initiation sites in the epididymis were localized by primer extension. The promoter of the gene does not contain a conventional TATA box immediately up-stream of the start site; rather, the sequence TATCA occurs at residue -35. Two CAAT boxes in opposite orientation and two putative binding sites for the transcription factor Sp1 were identified up-stream of the TATA-like box. To localize the cis-acting sequences responsible for androgen regulation of expression, fragments of the arMEP24 gene promoter region were cloned in front of the luciferase (LUC) reporter gene and cotransfected with an androgen receptor expression vector into CV-1 cells in a transient assay. LUC activities of CV-1 cells grown in the presence of various concentrations of 5 alpha-dihydrotestosterone were compared to LUC activities of untreated controls. The DNA fragment containing up to 200 nucleotides up-stream from the major transcription start site was sufficient for the full promoter activity, but not for the responsiveness to androgen induction. Depending on the 5 alpha-dihydrotestosterone concentration, a 2- to 4-fold induction of LUC activity was found if a -1797 to -167 arMEP24 gene fragment was used linked to the reporter gene driven by either the homologous promoter or the heterologous thymidine kinase promoter. Two or three copies of the imperfect palindromic sequence TGTTGAgagAGAACA, found at position -896 to -882 in the gene and resembling the consensus steroid hormone-responsive element, are able to confer androgen regulation to the thymidine kinase promoter independently of their orientation. These findings support evidence that transcriptional regulation of the arMEP24 gene occurs via the sequence TGTTGAgagAGAACA. Homologies found in the sequence up-stream of the promoter with several putative binding sites for erythroid-specific trans-acting regulatory proteins are discussed. Finally, the arMEP24 gene is located by in situ hybridization in the [A2-A4] region of mouse chromosome 13.
Mol Endocrinol 1993 Feb
PMID:Structural organization and regulation of the gene for the androgen-dependent glutathione peroxidase-like protein specific to the mouse epididymis. 846 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>