UNIPROT:P36969 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of selenium deprivation on the viability of murine L1210 cells exposed to various exogenous lipid hydroperoxides has been investigated. Selenoperoxidase activities of cells grown for longer than 1 week in 1% serum with no added selenium [Se(-) cells] were less than 10% of the activities of selenium-satisfied controls [Se(+) cells] or selenium-repleted counterparts [Se(-/+) cells]. The enzymes measured were classical glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX). Se(-) cells exhibited a compensatory increase in catalase activity. Dye exclusion and clonal survival assays indicated that Se(-) and Se(+) cells were relatively insensitive to photochemically generated phospholipid hydroperoxides in liposomal form. However, both cell types were sensitive to liposomal cholesterol hydroperoxides, e.g., 7-hydroperoxycholesterol (7-OOH), Se(-) being much more so (LD50 approximately 10 microM) than Se(+) (LD50 approximately 75 microM). By contrast, 7-hydroxycholesterol over a comparable concentration range was minimally toxic to Se(-) and Se(+) cells. Cell killing by 7-OOH was inhibited by desferrioxamine and by butylated hydroxytoluene, suggesting that iron-mediated free radical reactions are involved. The involvement of glutathione in cytoprotection was confirmed by showing that Se(+) cells were more sensitive to 7-OOH after treating with buthionine sulfoximine, an inhibitor of GSH synthesis. Cellular detoxification of 7-OOH is provisionally attributed to PHGPX rather than GPX, since 7-OOH and other cholesterol hydroperoxides were found to be good substrates for PHGPX in a cell free system, but were unreactive with GPX.
...
PMID:Lethal damage to murine L1210 cells by exogenous lipid hydroperoxides: protective role of glutathione-dependent selenoperoxidases. 189 56

We have previously identified and characterized GSHPx-GI, which is a cellular selenium-dependent glutathione peroxidase (GSHPx) distinct from the classic GSHPx-1 and phospholipid hydroperoxide glutathione peroxidase (PHGPX). We have determined the level of GSHPx-GI mRNA expression in the rat gastrointestinal tract from esophagus to colon. Although GSHPx-GI mRNA is readily detectable throughout the GI tract, the highest level is detected in the ileum and cecum. We have also determined the levels of GSHPx-GI mRNA expression and several antioxidant enzyme activities along the villus-to-crypt axis in the rat small intestine by cell fractionation. GSHPx-GI mRNA is present at a similar level in all of the epithelial fractions, whereas GSHPx-1 mRNA is detectable only in the remnant. This suggests that GSHPx-GI is the major cellular tetrameric GSHPx expressed in intestinal epithelium, and the expression of GSHPx-GI in the GI tract is not likely regulated differentially through maturation of epithelial cells. In terms of enzymatic activity, although we detected lower glutathione S-transferase activity in the crypt epithelium, there was a marginal increase of PHGPX activity, a twofold increase of GSHPx activity, and a three- to fivefold increase of catalase activity in the crypt relative to the distal villus. Thus, the crypt epithelial cells may be better protected from peroxidative damage.
...
PMID:The expression of an intestinal form of glutathione peroxidase (GSHPx-GI) in rat intestinal epithelium. 748 90

We report a transient adaptation to the oxidative stress of hydrogen peroxide (H2O2) exposure in several mammalian cell lines: Chinese hamster ovary fibroblast (CHO) cells, HA-1 cells (a defined CHO subclone), C3H 10T1/2 cells (embryonic mouse fibroblasts), V79 cells (Chinese hamster lung fibroblasts), and Clone 9 liver cells (rat liver epithelial cells). Up to 40-fold adaptive increases in resistance to H2O2 challenge occurred following pretreatment with relatively low H2O2 "priming" doses, from as little as 1.9% cell viability for untreated cells to as much as 76.5% viability for H2O2 pretreated cells. Detailed studies with HA-1 cells revealed the following pattern of responses to H2O2: very low H2O2 concentrations of 0.1 to 0.5 mumol/10(7) cells (3 to 15 microM) stimulated cell growth by 25 to 45%; low H2O2 concentrations of 2-5 mumol/10(7) cells (120 to 150 microM) induced a temporary growth-arrest, a lengthening of cell cycle from 18 h to approximately 26 h, and marked adaptive increases in H2O2 resistance; intermediate H2O2 concentrations of 9 to 14 mumol/10(7) cells (250 to 400 microM) caused permanent growth-arrest (i.e., permanent loss of replicative or divisional competence) with no evidence of necrosis; high H2O2 concentrations of 30 mumol/10(7) cells or greater (> or = 1 mM) caused an apoptotic-like necrotic cell death and destruction. The adaptive response to low H2O2 concentrations of 2-5 mumol/10(7) (120 to 150 microM) was maximal 18 h after pretreatment of HA-1 cells, declined thereafter toward baseline sensitivity, and was observed with both 7-day fix and stain procedures and clonogenic viability assays. Transient adaptation following H2O2 pretreatment of 4.15 mumol/10(7) (150 microM) involved the de novo synthesis of at least 20 proteins and was blocked by the translation inhibitor, cycloheximide. During the 18-h adaptation in HA-1 cells proteins were synthesized in three phases; early (0-4 h), middle (4-8 h), and late (8-15 h). No H2O2 response proteins were synthesized beyond 18 h after pretreatment, by which time adaptation had already maximized. Selective translational inhibition of the early, middle, or late proteins revealed that all three sets were necessary for a maximal adaptive increase in H2O2 resistance. Northern blot and enzyme activity analyses revealed no significant increases in transcription or translation of the classical antioxidant enzymes catalase, glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, Cu, Zn superoxide dismutase, or Mn superoxide dismutase in H2O2-adapted HA-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Transient adaptation of oxidative stress in mammalian cells. 772 66

Murine leukemia L1210 cells grown for 2-3 weeks in the presence of 1% serum without selenium supplementation [L.Se(-) cells] typically exhibited < 10% of the glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activity of selenium-satisfied controls [L.Se(+) cells]. Concomitant with diminished GPX and PHGPX activity was a 1.5- to 2.0-fold increase in catalase (CAT) activity, which reverted to control levels when L.Se(-) cells were given sufficient Se for full expression of selenoperoxidase activity. Selenium manipulation affected total glutathione content similarly, but had no effect on glutathione-S-transferase or superoxide dismutase activity. Long-term growth under Se-deficient conditions resulted in a progressive additional increase in CAT activity, which maximized after ca. 5 months. These cells [referred to as L'.Se(-)] attained CAT activity levels at least 100-times greater than those of Se-supplemented [L'.Se(+)] controls, whereas their glutathione content remained elevated by approximately 70%. Supplying L'.Se(-) cells with Se resulted in a rapid elevation to full GPX activity; however, CAT failed to decline in this case, suggesting that a selection for stable CAT hyperexpressing variants had been accomplished. Quantitative immunoblot analysis indicated that the high CAT activity of L'.Se(-) cells is accounted for by an elevated level of enzyme protein. Induction of CAT and selection for CAT-rich phenotypes, as apparent for Se-starved L1210 cells, was not observed in human K562 counterparts, which lack GPX and express only a low level of PHGPX. L.Se(-) cells were found to be more sensitive to H2O2-induced killing than L.Se(+) controls, whereas L'.Se(-) cells were exceedingly more resistant to H2O2 than L'.Se(+) counterparts. By contrast, L.Se(-) and L'.Se(-) cells were both more sensitive to t-butyl hydroperoxide than Se(+) controls, consistent with CAT being unimportant in the detoxification of this peroxide compared with GPX. This appears to be the first reported evidence for CAT hyperexpression in response to selenium deprivation.
...
PMID:Hyperexpression of catalase in selenium-deprived murine L1210 cells. 834 49

The testis is known to be highly sensitive to a number of physical stresses. Previous investigations suggest that oxidative stress may be an important mediator of testicular injury. The ability of the testis to manage oxidative stress may be limited by enzymatic clearance of reactive oxygen species (ROS). To evaluate the ability of the testis to withstand the common pathologic conditions of cryptorchidism and obstruction, we measured mRNA levels of testicular antioxidant enzymes. Prepubertal rats were rendered unilaterally cryptorchid and 40 days after the procedure, cryptorchid, contralateral and control (sham) testes were harvested for RNA extraction. Adult rats were subjected to unilateral efferent duct ligation and the obstructed testes harvested 1 to 28 days after the procedure. Antioxidant enzyme mRNA expression was assessed by Northern blot analysis using 32P-labeled DNA probes for classical cellular glutathione peroxidase (GSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGPX), Cu/Zn superoxide dismutase (SOD) and catalase. In both cryptorchid and contralateral testes, the germ cell-specific 0.9 kb SOD and PHGPX mRNA transcript levels were significantly decreased compared to control testes (p < 0.05). Similarly, after efferent duct ligation, the 0.9 kb SOD and PHGPX mRNA transcript levels also decreased compared to control testes (p < 0.05). These findings suggest that the overall decline in testicular mRNA transcript levels after efferent duct ligation and cryptorchidism is primarily due to germ cell depletion. Reduced levels of antioxidant enzyme mRNAs in cryptorchid testes have been documented. Further experiments may elucidate the role of increased oxidative stress associated with decreased antioxidants in cryptorchidism. It remains to be determined whether oxidative stress has a causative role in the abnormal spermatogenesis and tumorigenesis associated with cryptorchidism.
...
PMID:Cu/Zn superoxide dismutase, catalase and glutathione peroxidase mRNA expression in the rat testis after surgical cryptorchidism and efferent duct ligation. 922 87

Spermatozoa are highly sensitive to oxidative stress. The epididymis, a natural sperm reservoir, has maturational and storage functions. The epididymis may also protect spermatozoa from oxidative injury by elaborating scavengers of reactive oxygen species (ROS). Therefore, we have evaluated the mRNA expression of antioxidant enzymes in the normal rat epididymis and the effects of efferent duct ligation no the expression of these enzymes. Adult rat epididymides were harvested, divided into caput, corpus and cauda and processed for RNA extraction. Additional adult rats were subjected to unilateral efferent duct ligation and the epididymides harvested at 1, 4, 8, 16 or 28 days after the procedure. Antioxidant enzyme mRNA expression was assessed by Northern blot analysis using 32P-labelled DNA probes derived from known cDNA sequences for classical cellular glutathione peroxidase (GSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGPX), secretory epididymal glutathione peroxidase (E-GPX), copper-zinc superoxide dismutase (SOD), secretory epididymal superoxide dismutase (E-SOD) and catalase. Specific mRNA levels were measured, with gene expression evaluated relative to total RNA, not per organ. Variations in lane loading were controlled by measuring the levels of 28S ribosomal RNA. GSHPx, PHGPX, SOD and catalase mRNA were detected in the caput, corpus and cauda epididymis. E-GPX mRNA was only detected in the caput, whereas E-SOD mRNA was primarily detected in the corpus. At 28 days after efferent duct ligation, epididymal weight decreased by 34% relative to controls (p < 0.05). With the exception of PHGPX, the relative mRNA levels of the antioxidant enzymes studied did not change after efferent duct ligation. This study demonstrates that mRNAs for multiple antioxidant enzymes are expressed in the epididymis and that the relative expression of these enzymes remains largely unchanged in response to efferent duct ligation. Taken together, these results suggest that antioxidant enzymes may play an important, region-specific role in epididymal function. Expression of the secretory antioxidant enzymes E-SOD and E-GPX is region-specific, indicating that the need for antioxidant enzymes may vary along the length of the epididymis.
...
PMID:Identification and characterization of antioxidant enzyme mRNAs in the rat epididymis. 929 18

Antioxidant enzyme expression was determined in rat pancreatic islets and RINm5F insulin-producing cells on the level of mRNA, protein, and enzyme activity in comparison with 11 other rat tissues. Although superoxide dismutase expression was in the range of 30% of the liver values, the expression of the hydrogen peroxide-inactivating enzymes catalase and glutathione peroxidase was extremely low, in the range of 5% of the liver. Pancreatic islets but not RINm5F cells expressed an additional phospholipid hydroperoxide glutathione peroxidase that exerted protective effects against lipid peroxidation of the plasma membrane. Regression analysis for mRNA and protein expression and enzyme activities from 12 rat tissues revealed that the mRNA levels determine the enzyme activities of the tissues. The induction of cellular stress by high glucose, high oxygen, and heat shock treatment did not affect antioxidant enzyme expression in rat pancreatic islets or in RINm5F cells. Thus insulin-producing cells cannot adapt the low antioxidant enzyme activity levels to typical situations of cellular stress by an upregulation of gene expression. Through stable transfection, however, we were able to increase catalase and glutathione peroxidase gene expression in RINm5F cells, resulting in enzyme activities more than 100-fold higher than in nontransfected controls. Catalase-transfected RINm5F cells showed a 10-fold greater resistance toward hydrogen peroxide toxicity, whereas glutathione peroxidase overexpression was much less effective. Thus inactivation of hydrogen peroxide through catalase seems to be a step of critical importance for the removal of reactive oxygen species in insulin-producing cells. Overexpression of catalase may therefore be an effective means of preventing the toxic action of reactive oxygen species.
...
PMID:Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. 935 19

Mammalian caput and cauda epididymidal spermatozoa exhibit diverse stages of maturation, and their plasma membrane shows diverse composition and stability levels, thus enabling these spermatozoa to undergo the acrosomal reaction after transit through the epididymis. As a result, the study of antiperoxidative mechanisms is quite relevant, since epididymal spermatozoa must be properly protected against agents such as reactive oxygen species, which can impair the complex maturation process. We considered activities of certain enzymes (glutathione peroxidase [GPx], phospholipid hydroperoxide glutathione peroxidase [PHGPx], glutathione reductase [GR], superoxide dismutase [SOD], and catalase [CAT]) and the vitamin E content in isolated rat caput and cauda epididymidal spermatozoa. The results indicate that caput epididymidal sperm have significantly greater PHGPx (3.5x), GPx (2.4x), and SOD (1.7x) activities, as well as a greater amount of vitamin E (3.8x). There were no detectable differences in the GR and CAT activities of caput and cauda epididymidal spermatozoa. The substantial drop in PHGPx activity during epididymal transit is discussed in relation to an additional function of this enzyme: the use of caput sperm protamines as a sulfhydryl substrate. In vitro peroxidation of the two sperm populations by the free radical generator (azo-initiator) 2,2'-azobis(2-amidinopropane) dihydrochloride revealed that only about 13% of the vitamin E content of the caput epididymidal spermatozoa was consumed, which contrasts with the greater consumption (about 70%) of the vitamin in cauda epididymidal spermatozoa. Selective inhibition of PHGPx, SOD, or CAT did not change this picture. The higher susceptibility of cauda epididymidal spermatozoa to radicals is discussed in relation to the diverse enzymatic activities, vitamin E content, and peroxidative response. These factors are correlated with the different stages of sperm cell maturation, which are characterized-from caput to cauda epididymidis-by progressive destabilization of the plasma and acrosomal membranes.
...
PMID:Antioxidant systems in rat epididymal spermatozoa. 974 22

Vascular invasion of calcified cartilage, during endochondral ossification, is initiated and sustained by invasive cells (endothelial cells and macrophages) which degrade the tissue by releasing lytic enzymes. Concurrently, reactive oxygen species (ROS) are also released by these cells and we hypothesize that ROS also contribute to the degradation of the tissue. As a preliminary approach to this problem, the antioxidant activities and the effect of ROS on hypertrophic cartilage and chondrocytes (HCs) were investigated. Compared to resting or articular chondrocytes, HCs exhibited higher catalase but lower SOD specific activities and lower PHGPx concentration, thus revealing a defence activity specific against H2O2. Moreover, dose-dependent depletion of ATP occurred after few minutes of exposure to ROS, and a long-term treatment (16 h incubation with ROS) promoted the release of LDH activity and a significant variation of the poly- to mono-unsaturated fatty acid ratio. Finally, the incubation of HCs with low ROS doses induced the release of sedimentable alkaline phosphatase activity (matrix vesicles). How the obtained results fit the in vivo occurring events is discussed.
...
PMID:Sensitivity of chondrocytes of growing cartilage to reactive oxygen species. 981 64

Injury to the skin initiates a series of events including inflammation, new tissue formation, and matrix remodeling. During the early inflammatory phase, polymorphonuclear leukocytes and macrophages infiltrate the wounded tissue. Once activated, they produce large amounts of reactive oxygen species (ROS) as part of their defense mechanism. Although this process is beneficial, increased levels of ROS can inhibit cell migration and proliferation and can even cause severe tissue damage. Therefore, cells must develop strategies for the detoxification of these molecules. To gain insight into the mechanisms which underlie this process, we analyzed the temporal and spatial expression pattern of various ROS-scavenging enzymes during the healing process of full-thickness excisional wounds in mice. Here we demonstrate a strong mRNA expression of two types of superoxide dismutase (SOD), as well as of catalase, and the selenoenzymes glutathione peroxidase (SeGPx) and phospholipid hydroperoxide glutathione peroxidase in normal and wounded skin. Most importantly, mRNA levels of the SODs and of SeGPx increased strongly after skin injury. In situ hybridization and immunofluorescence studies revealed the presence of these transcripts at multiple places in the wound, whereby particularly high expression levels were detected in the hyperproliferative epithelium and the hair follicles at the wound edge. These data suggest an important role of ROS-scavenging enzymes in the detoxification of ROS during cutaneous wound repair.
...
PMID:Different types of ROS-scavenging enzymes are expressed during cutaneous wound repair. 1006 76

1 2 3 4 Next >>