Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differentiation of HL-60 cells by dimethylsulfoxide induces 5-lipoxygenase protein expression, but only low cellular 5-lipoxygenase activity. Similarly, B-lymphocytes express 5-lipoxygenase protein and show activity in cell homogenates but not in intact cells. Here, we demonstrate that suppression of cellular 5-lipoxygenase activity in these cell lines is serum dependent and that the serum effect can be mimicked by selenium. Selenium-dependent inhibition of 5-lipoxygenase activity was also observed in the corresponding cell homogenates or 100,000 x g supernatants when dithiothreitol or glutathione (GSH) was added. The properties of the endogenous selenium-dependent inhibitor, i.e., molecular mass, utilization of GSH and dithiothreitol as substrates, sensitivity to iodacetate, inhibition of 5-lipoxygenase activity in the presence of the GPx-1 inhibitor mercaptosuccinate, suggest that a selenoenzyme with properties of the phospholipid hydroperoxide glutathione peroxidase (GPx-4) is responsible for the 5-lipoxygenase inhibition in BL41-E95-A and immature HL-60 cells. Differentiation of HL-60 cells in the presence of 1,25-dihydroxyvitamin D3 and transforming growth factor-beta (TGF beta) upregulated cellular 5-lipoxygenase activity regardless of whether the cell were grown with or without serum or selenium. Also, 5-lipoxygenase activity in homogenates or 100,000 x g supernatants of 1,25-dihydroxyvitamin D3/TGF beta differentiated HL-60 cells and of human granulocytes was not inhibited by dithiothreitol or GSH. Thus, after 1,25-dihydroxyvitamin D3/TGF beta differentiation, HL-60 cells resemble normal granulocytes with respect to the high 5-lipoxygenase activity in intact cells and to the dithiothreitol effects in broken cell preparations. Combination experiments with 100000 x g supernatants of BL41-E95-A cells and neutrophils revealed that the high 5-lipoxygenase activity of granulocytes is due to stability of the 5-lipoxygenase catalytic activity against selenium-dependent peroxidases, but not to low peroxidase activity. Our data suggest that the capability of mature myeloid cells to release large amounts of leukotrienes after stimulation is due to a peroxidase-insensitive 5-lipoxygenase catalytic activity.
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PMID:Selenium-dependent peroxidases suppress 5-lipoxygenase activity in B-lymphocytes and immature myeloid cells. The presence of peroxidase-insensitive 5-lipoxygenase activity in differentiated myeloid cells. 895 58

Selenium is an essential nutrient and synthesis of selenoproteins is affected by limited selenium supply. During selenium deficiency there is a differential regulation of selenoprotein synthesis and gene expression; for example, there is a decrease in abundance of mRNA for cytosolic glutathione peroxidase (cGSH-Px) and a preservation of mRNA for phospholipid-hydroperoxide glutathione peroxidase (PHGSH-Px). This difference is not due to an alteration in the rate of transcription but might reflect differences in translation. The aim of the present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated regions (UTRs) in the regulation of selenoprotein mRNA stability and translation by using H4-II-E-C3 cells transfected with different constructs containing a type I iodothyronine deiodinase-coding region linked to different selenoprotein mRNA 3' UTRs. Translational efficiency results showed that the efficiency of the 3' UTRs in permitting selenocysteine incorporation is similar in selenium-replete conditions but, when selenium is limiting, the 3' UTR of cGSH-Px is less efficient than the 3' UTR of PHGSH-Px. The results suggest that the 3' UTR of these selenoprotein mRNA species influences their extent of translation when selenium levels are low. The different sensitivity of the 3' UTRs to selenium deficiency can explain the differential effect that selenium deficiency has on cGSH-Px and PHGSH-Px activity and mRNA levels, stability and translation. This might be partly responsible for channelling selenium for synthesis of PHGSH-Px rather than cGSH-Px.
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PMID:Role of the 3' untranslated region in the regulation of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase gene expression by selenium supply. 900 77

Selenium-dependent cellular glutathione peroxidase (GPX1) overexpressing [GPX1(+)] mice were derived by microinjecting a 5.3-kb cloned entire mouse GPX1 genomic DNA into fertilized eggs. The objective of this study was to determine the effect of GPX1 overexpression and dietary selenium on the expression of selenoperoxidases and the status of lipid peroxidation of these transgenic animals. An experiment with a 2 x 2 factorial arrangement of treatments with 15 GPX1(+) and 15 control mice (2 mo old) was conducted for 8 wk. Ten mice of each group (half males and females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) and five mice (three males and two females) were fed the basal diet supplemented with 0.51 mg Se/kg as Na2SeO3. The GPX1(+) mice had greater GPX1 activities (one- to sixfold, P < 0.0001) than the control mice at both levels of dietary selenium in all tissues except for liver, in which such difference (100%, P < 0.05) was observed only in Se-deficient mice. The GPX1 mRNA level in kidney and in lung of the Se-deficient GPX1(+) mice was 81% and 7.5-fold greater (P < 0.003) than the respective control level. Overexpression of GPX1 did not alter phospholipid hydroperoxide glutathione peroxidase (GPX4) activities and mRNA levels or glutathione S-transferase (GST) activities in most of the tissues, plasma glutathione peroxidase (GPX3) activity or plasma Se concentrations. No differences in lipid peroxidation in kidney, lung or intestine were observed between the Se-deficient GPX1(+) and control mice. In conclusion, the overexpression of the GPX1 gene in these mice was tissue specific and did not affect the expression of GPX3, GPX4 or GST and plasma Se levels; dietary Se appeared to affect the GPX1 overexpression at its mRNA level.
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PMID: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. 916 85

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.
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PMID:Cu/Zn superoxide dismutase, catalase and glutathione peroxidase mRNA expression in the rat testis after surgical cryptorchidism and efferent duct ligation. 922 87

Selenium-dependent cellular glutathione peroxidase (GPX1) knockout [GPX1(-)] mice were derived from 129/SVJ x C57BL/6 hybrid mice by microinjecting C57BL/6 blastocysts with recombinant embryonic stem cells carrying a target mutation in the GPX1 gene. Experiment 1 was conducted to determine the effects of the GPX1 knockout on the susceptibility of mice to dietary vitamin E and Se deficiency and on the expression of the Se-dependent plasma glutathione peroxidase (GPX3) and phospholipid hydroperoxide glutathione peroxidase (GPX4), and the Se-independent glutathione S-transferase (GST). Eleven GPX1(-) and 11 control mice (5 wk old, six males and five females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) or the basal diet supplemented with 0.5 mg Se/kg (as Na2SeO3) for 13 wk. Experiment 2 was conducted to determine the effect of the GPX1 knockout on the total Se concentration in the liver of Se-adequate mice. Six GPX1(-) and four control mice (5 wk old, half males and females) were fed the basal diet supplemented with 0.2 mg Se/kg and 15 mg of all-rac-alpha-tocopheryl acetate/kg for 5 wk. There was no difference in body weight gain or apparent susceptibility to dietary vitamin E and Se deficiency between the GPX1(-) and control mice. Knockout of GPX1 resulted in almost complete abolishment of GPX1 activity in various tissues, but had no effect on the GPX3 or GPX4 mRNA level and activity or the GST activity in several tissues at either level of dietary Se. The liver total Se concentration in the Se-adequate GPX1(-) mice was only 42% of that in the controls (P < 0. 0001). These results indicate that GPX1 is expressed independently of GPX3 or GPX4 and represents approximately 60% of the total hepatic Se in Se-adequate mice.
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PMID:Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues. 923 36

Various rat and human tissues and cell lines naturally exposed to endogenous or exogenous oxidative stress were examined for their pattern of selenoprotein transcripts. Selenoprotein P mRNA was mainly expressed in rat kidney, testis, liver and lung. In testis, a high phospholipid hydroperoxide glutathione peroxidase (PHGPx) but only a weak cytosolic glutathione peroxidase (cGPx) signal was obtained. In kidney, spleen, heart, liver and lung cGPx mRNA levels were higher than those of PHGPx and for both only weak signals were obtained with brain mRNA. The Northern blot results concerning the tissue distribution of cGPx in the rat were fully supported by activity measurements. None of the human tissues revealed a PHGPx mRNA signal, whereas selenoprotein P transcripts were present in all human tissues with the highest abundance in heart, liver, and lung, tissues which also exhibited strong cGPx signals. The gastrointestinal glutathione peroxidase (GPx-GI) was only expressed in human liver and colon liver. Liver, the organ that showed the broadest repertoire of selenoproteins, has to cope with reactive oxygen intermediates produced during detoxification reactions. Human cell lines of the myeloic system that may be exposed to oxidative stress during inflammatory processes showed distinct cGPx signals: epithelial cells showed low cGPx signals. Similar cGPx mRNA levels were found in normal human thyroid tissue and thyroid carcinoma cells. Among the human cell lines selenoprotein P expression was detected in HepG2 and HTh74 thyroid cells. Our data confirm the necessity of getting specific information on distinct tissue- and cell-specific patterns of selenoprotein expression as endpoints of selenium supply and biological function of the selenoprotein family. Analysis of total selenium contents of tissues or body fluids only provides integrative information on the global selenium status of individuals.
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PMID:Expression of selenoproteins in various rat and human tissues and cell lines. 928 88

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.
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PMID:Identification and characterization of antioxidant enzyme mRNAs in the rat epididymis. 929 18

In the blood fluke Schistosoma mansoni a functionally active, monomeric, phospholipid hydroperoxide glutathione peroxidase (PHGPx) has been purified and characterized. This enzyme contains a catalytically active selenocysteine. The protein has been shown to be the product of a cloned gene, previously referred to as a glutathione peroxidase gene. S. mansoni PHGPx has been found 5 times more abundant in female than in male worm extract. As in vertebrate PHGPx, homology alignment indicates that the residues involved in the glutathione binding by the tetrametric cellular glutathione peroxidase are mutated in the S. mansoni enzyme. Thus, this aspect appears a landmark of the PHGPx-type of glutathione peroxidases, which might be of functional relevance.
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PMID:Product of the Schistosoma mansoni glutathione peroxidase gene is a selenium containing phospholipid hydroperoxide glutathione peroxidase (PHGPx) sharing molecular weight and substrate specificity with its mammalian counterpart. 931 12

Adequate dietary iodine supplies and thyroid hormones are needed for the development of the central nervous system (CNS) and brown adipose tissue (BAT) function. Decreases in plasma thyroxine (T4) concentrations may increase the requirement for the selenoenzymes types I and II iodothyronine deiodinase (ID-I and ID-II) in the brain and ID-II in BAT to protect against any fall in intracellular 3,3',5 tri-iodothyronine (T3) concentrations in these organs. We have therefore investigated selenoenzyme activity and expression and some developmental markers in brain and BAT of second generation selenium- and iodine-deficient rats. Despite substantial alterations in plasma thyroid hormone concentrations and thyroidal and hepatic selenoprotein expression in selenium and iodine deficiencies, ID-I, cytosolic glutathione peroxidase (cGSHPx) and phospholipid hydroperoxide glutathione peroxidase (phGSHPx) activities and expression remained relatively constant in most brain regions studied. Additionally, brain and pituitary ID-II activities were increased in iodine deficiency regardless of selenium status. This can help maintain tissue T3 concentrations in hypothyroidism. Consistent with this, no significant effects of iodine or selenium deficiency on the development of the brain were observed, as assessed by the activities of marker enzymes. In contrast, BAT from selenium- and iodine deficient rats had impaired thyroid hormone metabolism and less uncoupling protein than in tissue from selenium- and iodine-supplemented animals. Thus, the effects of selenium and iodine deficiency on the brain are limited due to the activation of the compensatory mechanisms but these mechanisms are less effective in BAT.
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PMID:Selenium and iodine deficiencies: effects on brain and brown adipose tissue selenoenzyme activity and expression. 941 60

Selenium deficiency causes further impairment of thyroid hormone metabolism in iodine-deficient rats and therefore could have a role in the aetiology of both myxoedematous and neurological cretinism in humans. Thyroidal type I iodothyronine deiodinase (ID-I), cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase activities were increased in iodine-deficient adult rats and their offspring at 11 days of age. Thyroidal ID-I activity was unchanged and thyroidal cytosolic glutathione peroxidase activity was decreased by more than 75% by combined selenium and iodine deficiency in 11-day-old rats, indicating that, while the thyroid retained an ability to produce 3,3',5-triiodothyronine (T3), the gland was probably more susceptible to peroxidative damage caused by increased hydrogen peroxide concentrations driven by increased thyrotrophin. Thyroidal atrophy, common in myxoedematous cretinism, did not occur in iodine- or selenium and iodine-deficient rat pups. Iodine deficiency increased brain type II iodothyronine deiodinase activity 1.5-fold in 4-day-old rats and 3-fold in 11-day-old rats, regardless of selenium status. Thus rats were able to activate compensatory mechanisms in brain that would maintain T3 concentrations in selenium and iodine deficiencies. Surprisingly, however, selenium deficiency had a greater effect than iodine deficiency on markers of brain development in rat pups. Expression of the brain-derived neurotrophic factor (BDNF) mRNA was decreased in selenium deficiency in 4- and 11-day-old pups and in combined selenium and iodine deficiency in 4-day-old pups. Iodine deficiency caused an increase in BDNF expression in 11-day-old pups but had no effect on 4-day-old pups. Myelin basic protein mRNA expression in brain was decreased by combined selenium and iodine deficiency in 11-day-old rats.
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PMID:Selenoprotein expression and brain development in preweanling selenium- and iodine-deficient rats. 958 35


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