Disease relevance of GPX1

• The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer [1].
• Despite its largely referenced beneficial effects for cells, GSH was toxic for ECV304 cells in a dose-dependent manner but GSH-induced toxicity was reduced in selenium supplemented cultures and completely abolished in ECV304 overexpressing GPX1, compared to control [2].
• We found no significant association between the GPX1 genotypes and prostate cancer [3].
• DESIGN AND METHODS: Data from two population-based, case-control studies of lymphoma in the UK (700 cases and 915 controls) and USA (1593 cases and 2517 controls) were pooled to analyze polymorphisms in genes involved in the oxidative stress response (SOD2 Val16Ala, CAT C-262T and GPX1 Pro197Leu) [4].
• The GPX1 197Leu allele was weakly associated with NHL and follicular lymphoma [4].

Psychiatry related information on GPX1

• In conclusion our results suggest that increased activities of erythrocyte GPx and decreased erythrocyte GR activities might be due to lesser physical activity of children with CP [5].
• The activities of superoxide dismutase, catalase and glutathione peroxidase, three enzymes that contribute to the cellular defenses against free radical damage, were measured in different areas of autopsy brains from patients with Alzheimer's disease and from age matched controls [6].
• Catalase, superoxide dismutase and glutathione peroxidase activities of lung and liver during human development [7].
• However, the myocardium has a series of defense mechanisms including the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase plus other endogenous antioxidants such as vitamin E, ascorbic acid, and cysteine to protect the cell against the cytotoxic oxygen metabolites [8].
• The effect of SO(2) was examined on active avoidance learning, thiobarbituric acid reactive substances (TBARS), and the activities of Cu, Zn superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in young (3 months), middle-age (12 months ), and old (24 months) Swiss male albino rats [9].

High impact information on GPX1

• A candidate selenoprotein homologous to glutathione peroxidase was deduced from the sequence of molluscum contagiosum, a poxvirus that causes persistent skin neoplasms in children and acquired immunodeficiency syndrome (AIDS) patients [10].
• MCV possesses 59 genes that are predicted to encode previously uncharacterized proteins, including major histocompatibility complex class I, chemokine, and glutathione peroxidase homologs, which suggests that there are MCV-specific strategies for coexistence with the human host [11].
• Ovothiol replaces glutathione peroxidase as a hydrogen peroxide scavenger in sea urchin eggs [12].
• Erythrocyte glutathione peroxidase and myocardial infarction [13].
• In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 +/- 8.4 U/g of hemoglobin and 28.0 +/- 8.1 U/g of hemoglobin, respectively) [14].

Chemical compound and disease context of GPX1

• In summary, GPX1 overexpression delays cell growth and protects them from GSH and H(2)O(2) toxicity [2].
• Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma [15].
• We selectively investigated the interaction of seleno-glutathione peroxidase-1 (GPx-1), the major enzyme responsible for peroxide detoxification in mammalian cells, with the cytotoxic response of T47D human breast cancer cells to doxorubicin, an anticancer drug known to promote production of ROS and apoptotic mediator ceramide [16].
• Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations [17].
• GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells [18].

Biological context of GPX1

• Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1 [19].
• However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024) [20].
• In situ hybridization localized the human GPX1 gene to a single site on chromosome 3, at region 3q11-13 [21].
• 1. Thus, three genomic sites bear sequence homology to the GPX1 cDNA, and the one most homologous maps to 3q11-13.1 [21].
• As GPX1 overexpression could drain the cellular reduced glutathione (GSH) pool, we also tested the effects of extracellular GSH supplementation on cell growth [2].

Anatomical context of GPX1

• Thus, we investigated the potentially protective effects of GPX1 overexpression in the endothelial cell line, ECV304 [2].
• Assignment of the ARHA and GPX1 genes to human chromosome bands 3p21.3 by in situ hybridization and with somatic cell hybrids [22].
• METHODS: MnSOD, GPX1, and catalase activities were measured in isolated erythrocytes of 231 healthy, non-smoking student volunteers (55% women, ages 17-21, majority Asian or Caucasian) [23].
• More important from a therapeutic point of view, U937 and HL-60 cells, which require high concentrations of As(2)O(3) to undergo apoptosis, become sensitive to low, clinically acceptable concentrations of As(2)O(3) when cotreated with these GPx and catalase inhibitors [24].
• Expression of selenium-dependent glutathione peroxidase in human breast tumor cell lines [25].

Associations of GPX1 with chemical compounds

• The 26- and 21-kDa proteins were identified in immunoblot assays as the glutathione peroxidase (cGPX or GPX1) subunit and phospholipid hydroperoxide glutathione peroxidase (PHGPX or GPX4), respectively [26].
• Our results indicate selective induction of the GPX1 gene by BLM and different redox responses to BLM between WI38 and VA13 cells [27].
• GPX1 protein and activity level was not consistently detectable in H1703 cells, with or without Se supplementation; its mRNA was present but very low [28].
• During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage [29].
• The biological roles of the essential micronutrient Se are attributed to its presence in a range of 20-30 selenoproteins including the cytosolic and phospholipid hydroperoxide glutathione peroxidases (GPX1 and GPX4) [30].
• Glutathione peroxidase-1 (GPx-1), a selenocysteine-containing antioxidant enzyme, may be a key target of Hcy's deleterious actions, and several experimental and clinical studies have demonstrated a complex relationship between plasma total homocysteine (tHcy), GPx-1, and endothelial dysfunction [31].

Physical interactions of GPX1

• GSHPx coupled to reduced nicotine adenine diphosphate (NADPH) regenerating systems via glutathione reductase is virtually able to guarantee an effective protection of biological structures against oxidative attack (22) [32].
• Consensus p53 binding sequences were identified in human MnSOD and GPx promoter regions [33].
• Recombinant DNA-binding protein B binds the selenocysteine insertion sequence elements from the GPX1 and type I iodothyronine 5'-deiodinase genes in RNA electrophoretic mobility shift assays and competes with endogenous GPX1 selenocysteine insertion sequence binding activity in COS-1 cytosol extracts [34].
• The production of hydroperoxide derivatives of the linoleic and docosahexaenoic acids were determined by NADPH oxidation coupled to the activity of glutathione peroxidase, and also by production of thiobarbituric acid reactive substances [35].
• In RNA electromobility shift assays, nucleolin binds the selenocysteine insertion sequence from the human cellular glutathione peroxidase gene, competes with binding activity from COS cells, and shows diminished affinity for probes with mutations in functionally important, conserved sequence elements [36].

Enzymatic interactions of GPX1

• The rate of 14CO2 evolution, when the cells were subsequently incubated with 14C-labeled glucose, provided a measure of the rate at which NADPH was being oxidized by the glutathione peroxidase/reductase system for the disposal of H2O2 [37].
• G-6-PD-deficiency is a genetic disorder of erythrocytes in which the inability of affected cells to maintain NAD(P)H levels sufficient for the reduction of oxidized glutathione results in inadequate detoxification of hydrogen peroxide through glutathione peroxidase [38].

Regulatory relationships of GPX1

• Overexpression of catalase, superoxide dismutase, or glutathione peroxidase also inhibited FN-f-stimulated MMP-13 production [39].
• PU.1 regulates glutathione peroxidase expression in neutrophils [40].
• N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production [41].
• In addition, hGST 5.8 expressed glutathione peroxidase activity toward phospholipid hydroperoxides and GSH-conjugating activity toward 9,10-epoxy stearic acid [42].
• IL-8 production in oxidized-LDL-treated cells was mediated by reactive oxygen species, as it was partially inhibited by catalase and completely inhibited by glutathione peroxidase and N-acetylcysteine (p < 0.01) [43].

Other interactions of GPX1

• Even at very low H2O2 concentrations GPO reaches only approximately 8% of the rate at which catalase simultaneously degrades H2O2 [44].
• Levels of GSTP1, GSTM3, and GSHPx were significantly (P < 0.05) lower in NBECs from subjects with bronchogenic carcinoma [15].
• Both observations weaken the proposed inverse correlation between ER status and GPX-1 production [25].
• Further, the gene expression index formed by multiplying the values for mGST x GSTM3 x GSHPx x GSHPxA x GSTP1 had a sensitivity (90%) and specificity (76%) for detecting NBECs from bronchogenic carcinoma subjects that was better than any individual gene [15].
• Under HG, there was a twofold increase in the expression of CAT, CuZnSOD, and GPX mRNA in the patients without complications and the control subjects versus patients with nephropathy (P < 0.0001), and MnSOD did not change in any of the groups [45].

Analytical, diagnostic and therapeutic context of GPX1

• Northern blot analysis indicated that the increase in GPX activities was due to increased transcript levels of GPX1 but not GPX4 in both cells [27].
• RESULTS: There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001) [20].
• Southern blot analysis of human genomic DNA with the GPX1 cDNA showed that restriction endonucleases without sites in the probe sequence produced three hybridizing bands at standard stringency, diminishing to one strongly and one weakly hybridizing band at high stringency [21].
• ECV304 were stably transfected with the GPX1 cDNA and used for quantification of Bax (pro-apoptotic) and Bcl-2 (antiapoptotic) mRNA and protein levels, by quantitative RT-PCR and Western-blot [46].
• Utilizing simulated data in the context of two genomic regions GPX1 and GPX3, we evaluate the validity of the proposed test for small sample sizes and study its power in the presence and absence of missing genotype data [47].

References