Disease relevance of Gsr

• For the C6 glioma cells, GPx and GR activities were 1.29+/-0.14 and 1.07+/-0.11mumol/mgprotein/min, respectively [1].
• The prolonged inhibition of glutathione reductase by BCNU suggested this drug might enhance pulmonary oxygen toxicity by diminishing the lung's antioxidant capacity [2].
• Recombinant GR, an FAD-containing homodimer, corresponds in its enzymic and spectral properties to GR isolated from murine Ehrlich ascites tumor cells [3].
• Some of the investigated parameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reductase and NADPH-dependent diaphorase) were statistically significant [4].
• The observed increase in lipid peroxidation after MC treatment in MX-1 human mammary carcinoma implanted in the nude mice could result from the observed inhibited glutathione reductase activity [5].

High impact information on Gsr

• Glutathione peroxidase activity and mRNA level, glutathione reductase activity, and reduced glutathione levels were all transiently increased in hydroxyurea-treated cells, whereas the increase in glutathione-S-transferase activity was sustained [6].
• The effect of glutathione and a glutathione reductase inhibitor on the antitumor effect of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS) was studied [7].
• Studies of B6 Csf1(op/op) (lacking macrophages) mice, Rag1(-/-) mice, and wild-type mice treated with neutrophil-specific Gr1 mAbs, disclosed that macrophages but not lymphocytes or neutrophils are necessary [8].
• We propose that the oxidation of glutathione proceeds by reaction with protein disulfide groups to yield protein sulfhydryl (PSH) and a mixed disulfide of glutathione and protein; the mixed disulfide is capable of being reduced by glutathione reductase and NADPH, yielding the original PSH and GSSG, which is extruded from the lens [9].
• The LETS protein segregated concordantly with the chromosome 8 enzyme marker glutathione reductase (EC 1.6.4.2) and human chromosome 8 [10].

Chemical compound and disease context of Gsr

• This was supported by the finding that inhibition of GR activity with 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) increased H(2)O(2) toxicity in WT neurons over the same exposure period [11].
• 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 [12].
• Examination of brain cortex from mice killed at these stages of O2 toxicity revealed no change in oxidized glutathione (GSSG), non-protein sulfhydryls (NPSH), total glutathione (GSH + GSSG), the GSH/GSSG ratio, glutathione reductase and glutathione peroxidase [13].
• In Dalton lymphoma cells, the activities of glutathione S-transferase, glutathione peroxidase, and catalase decreased very distinctly (approximately 2-5, 2-5 and 5-11 times, respectively) at all time points, but glutathione reductase decreased significantly only at 72 h of cisplatin treatment [14].
• The activities of glutathione reductase and glutathione-S-transferase (ethacrynic acid) however were elevated with rotavirus infection in comparison to the control group [15].

Biological context of Gsr

• Notably, the SJL/J mouse strain possessed unique nucleotide substitutions in the Gsr and Sod2 genes, which led to Asp39Ala and Val138Met amino acid substitutions in GSR and SOD2, respectively [16].
• The results showed greater oxidative stress in SAMP8 than in SAMR1, largely because of a decrease in GSH levels and to an increase in GSSG and TBARS with the subsequent induction of the antioxidant enzymes GPX and GR [17].
• These type II diabetic mice were used to investigate the effects of Cinnamomi cassiae and Rhodiola rosea on blood glucose, reduced glutathione, glutathione reductase, glutathione S-transferase, glutathione peroxidase, lipid peroxidation, catalase and superoxide dismutase [18].
• GR showed significant decrease in expression at 1, 3 and 7 days in animals dosed with 0.5 LD50 MC-LR [19].
• These results suggest that DHA has distinct effects from AA and prevent H2O2-induced cell death by increasing the GSH levels mediated by the GPx and GR activities and PPP [20].

Anatomical context of Gsr

• The activities of GSH-Px and GSH-Re in corpora quadrigemina and GSH-Re in hypothalamus of Pb-exposure group did not decrease significantly [21].
• Among the enzymic antioxidants, superoxide dismutase activity decreased significantly (to 63.6% of initial activity for epidermis and 51.5% for dermis at 25 J), whereas activities of glutathione peroxidase and glutathione reductase decreased slightly [22].
• The activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase were determined in both hepatocytes and whole liver from the two age groups [23].
• The amino acid sequence deduced from the nucleotide sequences of the three subclones is identical with the known sequence of the mature glutathione reductase from human erythrocytes in all 478 positions [24].
• Although GR activities are found in mitochondria and cytoplasm, the sorting mechanisms of mammalian GR into mitochondria have not been elucidated [25].

Associations of Gsr with chemical compounds

• Glutathione reductase was inhibited immediately following irradiation with 1.0 microM hypericin, suggesting that an altered status of the glutathione pool contributed to cytotoxicity [26].
• Inhibition by hypericin in the dark was demonstrated for purified CuZnSOD, Se-dependent glutathione peroxidase, glutathione S-transferase, and glutathione reductase activities in vitro [26].
• Cinnamomi cassiae and Rhodiola rosea extracts significantly decreased on blood glucose, increased levels of reduced glutathione and the activities of glutathione reductase, glutathione S-transferase, glutathione peroxidase, catalase and superoxide dismutase in the liver [18].
• BHA has significantly induced the activities of GR and GSH in the present study [27].
• Only kidney GR activities (mean +/- S.E.M.) were significantly enhanced with the R diet (R, 61 +/- 2 vs. C, 54 +/- 3 U/mg protein; P = 0.03) [28].

Enzymatic interactions of Gsr

• Critical to such antioxidant functions are the ability to synthesize glutathione and keep it reduced via glutathione reductase and the ability to reduce oxidized-thioredoxin via thioredoxin reductase [29].
• Glutathione reductase catalyzes the NADPH-dependent conversion of glutathione disulfide to glutathione and helps protect the lung from injury by reactive oxygen [30].
• Application of TPA to mouse skin induces oxidative stress, as evidenced by numerous biochemical responses, including significant generation of H2O2 and enhanced levels of myeloperoxidase and oxidized glutathione reductase activities and decreases in glutathione levels and superoxide dismutase activity [31].

Regulatory relationships of Gsr

• Our findings suggest that in mouse spermatozoa, the enhanced glutathione reductase and peroxidase activities induced by the spontaneous lipid peroxidation increases NADPH production from the pentose phosphate shunt, while in rabbit spermatozoa, NADPH production is much lower [32].

Other interactions of Gsr

• GPx and catalase activities slowly went down, while GRed continued increasing as long as the levels of GSH were kept very low [33].
• After tumor transplantation and treatment with the complexes, the activities of GSH-Px and GSH-R were significantly lowered while SOD and G6PD activities were increased in EAC cells compared to their levels in EAC cells harvested from saline-treated mice [34].
• Aqueous black tea extract was given as a pretreatment to group IV mice at a dose of 200 mg ml(-1) polyphenols before the pesticide dose, which significantly decreased the levels of lipid peroxidation and significantly elevated the activities of SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the controls [35].
• Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice [36].
• The DKO cells had lower (P < 0.05) microsomal cytochrome P450 2E1 activities, but higher (P < 0.05) glutathione reductase and thioredoxin reductase activities than the WT cells at 0 hrs, and they responded differently to the APAP and NAPQI treatments [37].

Analytical, diagnostic and therapeutic context of Gsr

• The GR activity was only increased in the presence of 50 mug/ml of SRG compared to the control group [38].
• Erythrocyte and organo-somatic indices did not show differences between wild-types and homozygous mutants, indicating no association between the GR deficiency and haemolytic anaemia in this potential animal model [39].
• The molecular cloning of a partial cDNA to mouse glutathione reductase mRNA and of a full-length cDNA to the mRNA of the human enzyme is described [24].
• RT-PCR of mRNA from the Neu mice indicated a substantial deletion in the normal GR coding sequence [40].
• No significant changes were observed for superoxide dismutase, catalase, glutathione reductase, glutathione, uric acid, malondialdehyde (HPLC), or in vitro sensitivity to peroxidation in the kidney [41].

References