Identification of the Binding Site of Methylglyoxal on Glutathione Peroxidase: Methylglyoxal Inhibits Glutathione Peroxidase Activity via Binding to Glutathione Binding Sites Arg 184 and 185

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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