Disease relevance of GPX1

• Unlike H(2)O(2) toxicity, delayed toxicity of 18:3 toward gpx1 Delta/gpx2 Delta/gpx3 Delta cells was correlated with the gradual incorporation of 18:3 into S. cerevisiae membrane lipids and was suppressible with alpha-tocopherol, an inhibitor of lipid peroxidation [1].

High impact information on GPX1

• We identified the glutathione peroxidase (GPx)-like enzyme Gpx3 as a second component of the pathway, serving the role of sensor and transducer of the hydroperoxide signal to Yap1 [2].
• These data reveal a redox-signaling function for a GPx-like enzyme and elucidate a eukaryotic hydroperoxide-sensing mechanism [2].
• GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae [3].
• In the complete absence of peroxiredoxins, the expression of other antioxidant proteins including glutathione peroxidase and glutathione reductase was induced [4].
• The yeast prion protein Ure2 shows glutathione peroxidase activity in both native and fibrillar forms [5].

Biological context of GPX1

• The gpx3Delta mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes [6].
• Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae [6].
• When the basal diet was fed, sow serum GSH-Px activity declined from 6 d prepartum and remained low throughout lactation [7].
• When dietary Se levels increased, sow serum Se concentration and serum GSH-Px activity increased (P < .05) at both 7 and 14 d postpartum [7].
• Pigs were bled at 3-wk intervals and plasma Se, glutathione peroxidase (GSH-Px) activity, glutamic oxalacetic transaminase (PGOT), hemoglobin, packed cell volume, and blood cell Se concentration were measured [8].

Anatomical context of GPX1

• We propose a model in which the glutathione peroxidase activity of glutaredoxins converts hydroperoxides to their corresponding alcohols; these can then be conjugated to GSH by glutathione-S-transferases and transported into the vacuole by Ycf1 [9].
• Co-expression of the BI-GST/GPX protein brought the total glutathione levels back to normal and re-established the mitochondrial membrane potential but had no effect on the phospholipid alterations [10].
• In the group supplemented with selenium-yeast, the activities of GSH-Px, CAT, and SOD were significantly increased in erythrocytes, whereas GST activity and plasma content of GSH + GSSG were reduced compared with the controls [11].
• Testis GSH-Px activity increased from weaning to 145 kg BW even when Se was not added to the diet [12].
• The correlation between pancreas Se level and GSH-Px activity was .36 (P less than .05) [13].

Associations of GPX1 with chemical compounds

• Expression of the GPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation [6].
• Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Delta mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase [6].
• An S. cerevisiae gpx1 Delta/gpx2 Delta/gpx3 Delta mutant was defective for growth in medium supplemented with the oxidation-sensitive polyunsaturated fatty acid linolenate (18:3) [1].
• To discriminate between the selenium-dependent and the selenium-independent form, glutathione peroxidase activity has been measured with both H2O2 and cumene hydroperoxide [14].
• Serum collected at various intervals in gilts, sows, and progeny measured glutathione peroxidase activity and Se concentrations [15].

Other interactions of GPX1

• It was found that super oxide dismutase (SOD1 and SOD2), catalase and glutathione peroxidase (GPx) all are over expressed in CR [16].
• We recently reported that Grx1 is active as a glutathione peroxidase and can directly reduce hydroperoxides (Collinson, E. J., Wheeler, G. L., Garrido, E. O., Avery, A. M., Avery, S. V., and Grant, C. M. (2002) J. Biol. Chem. 277, 16712-16717) [17].

Analytical, diagnostic and therapeutic context of GPX1

• Both gel-filtration and dynamic light-scattering (DLS) results indicate that Gpx3 is a monomer in solution at a concentration of about 2 mg ml(-1), whereas glutathione peroxidases are normally tetrameric or dimeric [18].
• Purification, crystallization and preliminary X-ray analysis of glutathione peroxidase Gpx3 from Saccharomyces cerevisiae [18].
• After centrifugation of the yeast protoplast homogenates at 2500 x g for 10 min, 67% of total GPx activity was recovered from the supernatant (Sup. 1) and 33% was from the pellet (Pellet 1) [19].
• On the other hand, at least 12% of total GPx activity was recovered from the purified plasma membrane which was obtained from the Pellet 1 by successive sucrose density gradient centrifugation [19].
• 1 was fractionated by sucrose density gradient ultracentrifugation, GPx activity was essentially recovered from the mitochondria fraction [19].

References