The Selenium Requirement for Glutathione Peroxidase mRNA Level Is Half of the Selenium Requirement for Glutathione Peroxidase Activity in Female Rats

Selenoprotein P is a glycoprotein that contains greater than 60% of the selenium in rat plasma. Physiological experiments were undertaken to gain insight into selenoprotein P function. Selenium-deficient rats were injected with doses of selenium ranging from 25 to 200 micrograms/kg, and the appearance of selenoprotein P was compared with the appearance of glutathione peroxidase activity in plasma and in liver. Selenoprotein P concentration increased to 35% of control by 6 h, whereas glutathione peroxidase activity increased minimally or not at all. Moreover, in rats given 100 and 200 micrograms selenium/kg, selenoprotein P reached 75% of its concentration in control rats at 24 h, whereas glutathione peroxidase activity reached only 6% of control. Cycloheximide pretreatment blocked the appearance of selenoprotein P in response to selenium injection. Male and female rats had similar concentrations of selenoprotein P. Partially purified selenoprotein P and plasma glutathione peroxidase labeled with 75Se were administered intravenously to selenium-deficient and control rats. 75Se given as selenoprotein P disappeared more rapidly from plasma than did 75Se given as glutathione peroxidase. Selenium deficiency did not significantly affect 75Se disappearance from plasma. At 2 h, brain, but not other tissues, took up more 75Se in selenium-deficient rats than in control rats when 75Se was given as selenoprotein P. This suggests that brain has a specific uptake mechanism for selenium given in the form of selenoprotein P. These results demonstrate that several physiological properties distinguish selenoprotein P from glutathione peroxidase. However, they do not clearly indicate its function.

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The nature of the sex-linked differences in glutathione peroxidase activity and aerobic oxidation of glutathione in male and female rat liver

Biochemical Journal ◽

10.1042/bj1150449 ◽

1969 ◽

Vol 115 (3) ◽

pp. 449-456 ◽

Cited By ~ 65

Author(s):

R E Pinto ◽

W Bartley

Keyword(s):

Lipid Peroxidation ◽

Glutathione Peroxidase ◽

Rat Liver ◽

Peroxidase Activity ◽

Aerobic Oxidation ◽

Female Rats ◽

Ovariectomized Rats ◽

Female Rat ◽

Glutathione Peroxidase Activity ◽

Peroxide Formation

1. Glutathione peroxidase activity in the livers of sham-operated female rats was about 60% higher than in similarly treated male rats. The value in the ovariectomized female was about the same as that in the castrated or sham-operated male. 2. Glutathione peroxidase activity changed during the oestrous cycle. The highest value was in oestrus, and was about 50% higher than the lowest activity, which was found in dioestrus. The activity in proestrus and in metoestrus was respectively about 20 and 30% higher than in dioestrus. 3. In the pregnant female 1 or 2 days before term, glutathione peroxidase activity was about 20% higher than that in the female in oestrus. 4. Subcutaneous implants of both oestra-diol and progesterone in the gonadectomized rats increased the glutathione peroxidase activity approximately to the values found in the female at oestrus. 5. The rate of aerobic oxidation of GSH in the female rat liver was about 80% higher than in the male and about 110% higher than in the gonadectomized rats. Treatment of gonadectomized rats with subcutaneous implants of oestradiol and of progesterone increased the rate of oxidation of GSH by about 100%. 6. In the presence of azide the rate of GSH oxidation in the male and in the female was respectively about 3·5- and 2·1-fold that in the absence of azide. In castrated or ovariectomized rats the increase due to the presence of azide was about 2·4-fold. In the gonadectomized rats treated with oestradiol or progesterone the rate of GSH oxidation in the presence of azide was about 2·2-fold that in its absence. 7. The rate of lipid peroxidation in female was 15–30-fold that in male or in gonadectomized rats. Treatment of the gonadectomized rats with oestradiol or with progesterone increased the rate of lipid peroxidation up to values that were even higher than in the female. In the presence of GSH the formation of malonaldehyde from peroxides was virtually eliminated. 8. The results suggest that the sex-linked differences in glutathione peroxidase activity, in the rate of GSH oxidation and in the rate of lipid peroxidation are due to the female sex hormones. 9. It is suggested that both the catalase activity and the rate of hydrogen peroxide formation are higher in the male than in the female. 10. Sex-linked changes in glutathione peroxidase, in the rate of GSH oxidation and in the rate of lipid peroxide formation are discussed in relation to the metabolism of oestrogens in the liver and also to the possible nature of those sex-linked changes.

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Low Selenium Status in the Elderly Influences Thyroid Hormones

Clinical Science ◽

10.1042/cs0890637 ◽

1995 ◽

Vol 89 (6) ◽

pp. 637-642 ◽

Cited By ~ 64

Author(s):

Oliviero Olivieri ◽

Domenico Girelli ◽

Margherita Azzini ◽

Anna Maria Stanzial ◽

Carla Russo ◽

...

Keyword(s):

Glutathione Peroxidase ◽

Thyroid Hormones ◽

Peroxidase Activity ◽

Controlled Trial ◽

The Elderly ◽

Serum Selenium ◽

Selenium Status ◽

Glutathione Peroxidase Activity ◽

Double Blind ◽

Double Blind Placebo

1. Iodothyronine 5′-deiodinase, which is mainly responsible for peripheral triiodothyronine (T3) production, has recently been demonstrated to be a selenium-containing enzyme. In the elderly, reduced peripheral conversion of thyroxine (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid conditions of undernutrition or malnutrition, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. 3. In order to properly assess the influence of selenium status on iodothyronine 5′-deiodinase type I activity, a double-blind placebo-controlled trial was also carried out on 36 elderly subjects, resident at a privately owned nursing home. 4. In the free-living population, a progressive reduction of the T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age. A highly significant linear correlation between T4, T3/T4 and selenium was observed in the population as a whole (for T4, R = −0.312, P < 0.002; for T3/T4 ratio, R = 0.32, P < 0.01) and in older subjects (for T4, R = −0.40, P < 0.05; for T3/T4 ratio, R = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. 6. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.

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Selenium levels and glutathione peroxidase activity in patients with ataxia-telangiectasia: association with oxidative stress and lipid status biomarkers

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01732-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Itana Gomes Alves Andrade ◽

Fabíola Isabel Suano-Souza ◽

Fernando Luiz Affonso Fonseca ◽

Carolina Sanchez Aranda Lago ◽

Roseli Oselka Saccardo Sarni

Keyword(s):

Oxidative Stress ◽

Glutathione Peroxidase ◽

Peroxidase Activity ◽

Oxidized Ldl ◽

Reference Value ◽

Glutathione Peroxidase Activity ◽

Oxidative Stress Biomarkers ◽

Apo B ◽

Lipid Status ◽

And Oxidative Stress

Abstract Introduction Ataxia-Telangiectasia (A-T) is a multi-system disorder that may be associated with endocrine changes, oxidative stress in addition to inflammation. Studies suggest that selenium is a trace element related to protection against damage caused by oxidative stress. Objective To describe the plasma levels of selenium and erythrocyte glutathione peroxidase activity in A-T patients and to relate them to oxidative stress and lipid status biomarkers. Methods This is a cross-sectional and controlled study evaluating 22 A-T patients (age median, 12.2 years old) matched by gender and age with 18 healthy controls. We evaluated: nutritional status, food intake, plasma selenium levels, erythrocyte glutathione peroxidase activity, lipid status, inflammation and oxidative stress biomarkers. Results Adequate levels of selenium were observed in 24/36 (66.7%) in this evaluated population. There was no statistically significant difference between the groups in selenium levels [47.6 μg/L (43.2–57.0) vs 54.6 (45.2–62.6) μg/dL, p = 0.242]. Nine of A-T patients (41%) had selenium levels below the reference value. The A-T group presented higher levels of LDL-c, non-HDL-c, oxidized LDL, Apo B, Apo-B/Apo-A-I1, LDL-c/HDL-c ratio, malondialdehyde [3.8 µg/L vs 2.8 µg/L, p = 0.029] and lower Apo-A-I1/HDL-c and glutathione peroxidase activity [7300 U/L vs 8686 U/L, p = 0.005]. Selenium levels were influenced, in both groups, independently, by the concentrations of oxidized LDL, malonaldehyde and non-HDL-c. The oxidized LDL (AUC = 0.849) and ALT (AUC = 0.854) were the variables that showed the greatest discriminatory power between groups. Conclusion In conclusion, we observed the presence of selenium below the reference value in nearly 40% and low GPx activity in A-T patients. There was a significant, inverse and independent association between selenium concentrations and oxidative stress biomarkers. Those data reinforce the importance of assessing the nutritional status of selenium in those patients.

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The distribution, induction and isoenzyme profile of glutathione S-transferase and glutathione peroxidase in isolated rat liver parenchymal, Kupffer and endothelial cells

Biochemical Journal ◽

10.1042/bj2640737 ◽

1989 ◽

Vol 264 (3) ◽

pp. 737-744 ◽

Cited By ~ 18

Author(s):

P Steinberg ◽

H Schramm ◽

L Schladt ◽

L W Robertson ◽

H Thomas ◽

...

Keyword(s):

Endothelial Cells ◽

Glutathione Peroxidase ◽

Rat Liver ◽

Peroxidase Activity ◽

Cell Types ◽

Transferase Activity ◽

Glutathione Peroxidase Activity ◽

Glutathione S Transferase ◽

Liver Parenchymal ◽

Parenchymal Cells

The distribution and inducibility of cytosolic glutathione S-transferase (EC 2.5.1.18) and glutathione peroxidase (EC 1.11.1.19) activities in rat liver parenchymal, Kupffer and endothelial cells were studied. In untreated rats glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene and 4-hydroxynon-2-trans-enal as substrates was 1.7-2.2-fold higher in parenchymal cells than in Kupffer and endothelial cells, whereas total, selenium-dependent and non-selenium-dependent glutathione peroxidase activities were similar in all three cell types. Glutathione S-transferase isoenzymes in parenchymal and non-parenchymal cells isolated from untreated rats were separated by chromatofocusing in an f.p.l.c. system: all glutathione S-transferase isoenzymes observed in the sinusoidal lining cells were also detected in the parenchymal cells, whereas Kupffer and endothelial cells lacked several glutathione S-transferase isoenzymes present in parenchymal cells. At 5 days after administration of Arocolor 1254 glutathione S-transferase activity was only enhanced in parenchymal cells; furthermore, selenium-dependent glutathione peroxidase activity decreased in parenchymal and non-parenchymal cells. At 13 days after a single injection of Aroclor 1254 a strong induction of glutathione S-transferase had taken place in all three cell types, whereas selenium-dependent glutathione peroxidase activity remained unchanged (endothelial cells) or was depressed (parenchymal and Kupffer cells). Hence these results clearly establish that glutathione S-transferase and glutathione peroxidase are differentially regulated in rat liver parenchymal as well as non-parenchymal cells. The presence of glutathione peroxidase and several glutathione S-transferase isoenzymes capable of detoxifying a variety of compounds in Kupffer and endothelial cells might be crucial to protect the liver from damage by potentially hepatotoxic substances.

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