Disease relevance of Gpx3

• We previously constructed plasmids for synthesis of glutathione-peroxidase (GPx) mutants in an Escherichia coli expression system [1].
• After 6 weeks, body weight, HbA1c, plasma glucose, lipids, peroxylipid (malonedialdehyde, MDA), alpha-tocopherol and glutathione peroxidase 1 (GPx) mRNA expression in the kidney were measured [2].
• For the C6 glioma cells, GPx and GR activities were 1.29+/-0.14 and 1.07+/-0.11mumol/mgprotein/min, respectively [3].

High impact information on Gpx3

• Both GPx isoforms originate from a joint ph/snGPx gene, but their N-terminal peptides are encoded by alternative first exons [4].
• The decision, which GPx isoform is expressed in a given cell, appears to be made by alternative splicing of a joint primary transcript [4].
• In situ hybridization localized plasma GPx mRNA to proximal tubules, while primary cell culture demonstrated that plasma GPx is synthesized and secreted by proximal tubular epithelial cells [5].
• Plasma GPx mRNA was observed to be very abundant in kidney compared with placenta, epididymis, intestine, lung, heart, testis, ovary, salivary gland, spleen, thymus, stomach, brain, and fetal kidney and could not be detected in pancreas or in liver except from pregnant mice [5].
• The gastrointestinal isoenzyme (GI-GPx) is most related to cGPx and is exclusively expressed in the gastrointestinal tract [6].

Biological context of Gpx3

• Using a reverse transcription coupled to PCR amplification strategy, with degenerated primers localized in highly conserved domains of known glutathione peroxidase (GPX) proteins, we have generated, from mouse epididymal RNA, a cDNA fragment which was subsequently used to isolate a genomic clone encoding mouse plasma GPX (GPX3) [7].
• PURPOSE: We recently used microarray and reverse transcriptase PCR (RT-PCR) analysis to show an upregulation of cathepsin S (CatS) and glutathione peroxidase 3 (GPX3) in the aging mouse RPE/choroid [8].
• Exhaustive swimming exercise significantly increases the degree of lipid peroxidation in terms of malondialdehyde content and reduces the antioxidant activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) [9].
• Increased gene expression of glutathione peroxidase-3 in diabetic mouse heart [10].
• In order to elucidate the function of M-LPH1, we examined the mRNA levels of several enzymes involved in the metabolism of reactive oxygen species in COS-7 cells and found that transfection with M-LPH1 down-regulates expression of the plasma glutathione peroxidase and catalase genes [11].

Anatomical context of Gpx3

• To test for the consequences of GPx deficiency in astrocytes, astrocyte-rich primary cultures from wild-type and GPx1-deficient [GPx1(-/-)] mice were exposed to H(2)O(2) [12].
• Enhanced expression of plasma glutathione peroxidase in the thymus of mice treated with TCDD and its implication for TCDD-induced thymic atrophy [13].
• This is the first report that a particular isotype of the glutathione peroxidase family is regulated by TCDD at both mRNA and protein levels. pGPx is expressed in various tissues in contact with body fluids, and detoxifies hydrogen peroxides and lipid hydroperoxides [13].
• The fact that the knockout mice express normal levels of plasma GPX as well as testis and liver PHGPX activity indicates that animals are not selenium-deficient [14].
• CONCLUSIONS: The increases in mRNA levels for CatS and GPX3 found in the aging C57BL/6 RPE/choroid appear to represent an increase in both the numbers of cells expressing these messages and an increase in the level of expression in individual cells [8].

Associations of Gpx3 with chemical compounds

• No significant induction of cardiac GSH and GPx was observed with the above D3T treatment [15].
• Our findings revealed that chronic oral treatment with the extract elevates enzymatic activities of SOD and GPx accompanied by a corresponding decrease in malondialdehyde [9].
• 5 microg/ml actinomycin D, 30 microg/ml cycloheximide (de novo protein synthesis inhibitor) and 50 microg/ml acetovanilone (intracellular superoxide anion production inhibitor) had no effects in attenuating the induction of PLGPx expression by L929-CM [16].
• An inadequate selenium supply and corresponding increase of GPx activity upon selenite supplementation was also observed with other cell lines, for instance, D10N, ECV-304, HepG2, and THP-1 [17].
• Furthermore, we show here that androgen withdrawal by castration down regulates the expression of the GPx3 gene both in the epididymis and vas deferens while GPx3 expression in the kidney was found to be androgen-independent [18].

Other interactions of Gpx3

• Overexpression of cellular glutathione peroxidase does not affect expression of plasma glutathione peroxidase or phospholipid hydroperoxide glutathione peroxidase in mice offered diets adequate or deficient in selenium [19].
• It was found that Se exerts a statistically significant (p<0.05) effect only on GPx3 mRNA, referred to as the optical density (OD) ratio (GPx3/beta-actin) [20].
• Similarly, ozone-induced increases in lung CuZn-SOD and MnSOD activities were not observed in Cu-deficient mice, although lung GPx activity was increased in these mice relative to their air-breathing controls [21].
• Piperine supplementation to tumour-induced animals significantly lowered the phase-I enzymes (NADPH-C reductase, cyt-p450 and cyt-b5)) and there was a rise in glutathione-metabolizing enzymes (GPx, GR and G6PDH), which indicated an antitumour and anti-cancer effect [22].
• In Mpv17-/- cells, enzyme activity and mRNA expression (examined by quantitative RT-PCR) of membrane-bound gamma-glutamyl transpeptidase were increased, while plasma glutathione peroxidase and superoxide dismutase levels were lowered [23].

Analytical, diagnostic and therapeutic context of Gpx3

• Mouse plasma glutathione peroxidase. cDNA sequence analysis and renal proximal tubular expression and secretion [5].
• The level of expression of plasma GPx in various mouse tissues and during development was investigated by Northern blot analysis [5].
• On d 7, plasma GPx activity in the DSS group increased by 61% compared with the control group (p < 0.05) [24].
• METHODS: Eye sections from 2-month-old and 24-month-old C57BL/6 mice were probed for CatS or GPX3 mRNA by in situ hybridization [8].
• Finally, immunohistochemistry data reveals that within the epididymis GPx3 distribution is quite peculiar suggesting the existence in this organ of complex traductional and/or transcriptional regulatory processes [18].

References