scholarly journals Neonatal Selenoenzyme Expression Is Variably Susceptible to Duration of Maternal Selenium Deficiency

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 288
Author(s):  
Laura G. Sherlock ◽  
Durganili Balasubramaniyan ◽  
Lijun Zheng ◽  
Miguel Zarate ◽  
Thomas Sizemore ◽  
...  
Keyword(s):  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Deficient Diet ◽  
Hepatic Expression ◽  
Multiple Organs ◽  
Thioredoxin Reductase 1 ◽  
Neonatal Liver ◽  
Se Deficiency ◽  
The Impact ◽  
Gpx Activity

Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels, which increases the risk for neonatal morbidities. There is a hierarchy to selenoprotein expression after Se deficiency in adult rodents, depending on the particular protein and organ evaluated. However, it is unknown how limited Se supply during pregnancy impacts neonatal selenoprotein expression. We used an Se-deficient diet to induce perinatal Se deficiency (SeD), initiated 2–4 weeks before onset of breeding and continuing through gestation. Neonatal plasma, liver, heart, kidney, and lung were collected on the day of birth and assessed for selenoproteins, factors required for Se processing, and non-Se containing antioxidant enzymes (AOE). Maternal SeD reduced neonatal circulating and hepatic glutathione peroxidase (GPx) activity, as well as hepatic expression of Gpx1 and selenophosphate synthetase 2 (Sps2). In contrast, the impact of maternal SeD on hepatic thioredoxin reductase 1, hepatic non-Se containing AOEs, as well as cardiac, renal, and pulmonary GPx activity, varied based on duration of maternal exposure to SeD diet. We conclude that the neonatal liver and circulation demonstrate earlier depletion in selenoenzyme activity after maternal SeD. Our data indicate that prolonged maternal SeD may escalate risk to the neonate by progressively diminishing Se-containing AOE across multiple organs.

scholarly journals Antenatal Selenium Deficiency Decreases Neonatal Pulmonary Selenium-Containing Antioxidant Enzymes

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 713-713
Author(s):  
Durganili Balasubramaniyan ◽  
Lijun Zheng ◽  
Robyn De Dios ◽  
Eva Nozik ◽  
Clyde Wright ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Protein Content ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Nutritional Intervention ◽  
Activity Level ◽  
Enzyme Activity Assay ◽  
Oxidative Challenge ◽  
Se Deficiency ◽  
Gpx Activity

Abstract Objectives Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity. Selenium (Se) deficiency increases the risk for oxygen requirement at 28 days and BPD and thus may be a modifiable nutritional intervention. Se is an essential trace mineral that is incorporated into Se-containing antioxidant enzymes (AOE). An infant's Se status at birth is regulated by the mother's Se supply during pregnancy, however, it is unknown if any neonatal Se-containing AOE in the lung are decreased by antenatal Se deficiency. We hypothesize that antenatal Se deficiency will decrease neonatal pulmonary expression of Se-containing AOE. Methods C57Bl/6 mice were allocated to sufficient (SeS, 0.4 ppm Se) or deficient (SeD, < 0.01 ppm Se) diets before breeding. Breeding pairs were allowed to serially breed, and pups from the 1st-4th pregnancies were evaluated. Pups were sacrificed at PN0. Glutathione peroxidase (GPx) activity was measured in the lung by enzyme activity assay. Pulmonary GPx1, GPx3, thioredoxin reductase 1 (Trxrd1) and selenoprotein N (SelenoN) protein content were measured by Western blot. F and M pups were analyzed as separate groups. Results Weights were similar at postnatal day 0 (PN0) and PN4 for SeS and SeD pups, but by PN7 through adulthood, both male and female SeD mice weighed less then SeS mice. At PN0, pulmonary GPx activity was decreased in all SeD pups, with similar decreases in the protein content of both GPx1 and GPx3 (n = 6–10). We observed a progressive impact of SeD on the pups based on the dam's pregnancy. GPx activity and protein contents were more significantly decreased in pups born after a dam's 3rd or 4th pregnancy than the 1st or 2nd (n = 4–6). Trxrd1 and SelenoN protein content were not decreased in pups born after a dam's 1st or 2nd pregnancy (n = 4–6). However, both were decreased in the lungs of pups born to a dam's 3rd or 4th gestation (n = 6). Conclusions Neonatal pups exposed to antenatal SeD demonstrate decreased pulmonary GPx protein content and activity level without sex differences. Pups born to a SeD dam's third or fourth gestation exhibited a further decline in pulmonary Trxrd1 and SelenoN content. We speculate that SeD neonates may be vulnerable to pulmonary oxidative stresses secondary to low antioxidant enzymatic defense. Impaired ability to respond to oxidative challenge in the lung may predispose SeD infants to BPD. Funding Sources NIH/NHLBI.

scholarly journals The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Regina Brigelius-Flohé ◽  
Mike Müller ◽  
Doris Lippmann ◽  
Anna Patricia Kipp
Keyword(s):  
Cancer Cells ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Related Factor ◽  
Cellular Defense ◽  
Thioredoxin Reductase 1 ◽  
Cancer Initiation ◽  
Yin And Yang ◽  
Support Tumor Growth

The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage.

scholarly journals Thioredoxin Reductase-1 Inhibition Augments Endogenous Glutathione-Dependent Antioxidant Responses in Experimental Bronchopulmonary Dysplasia

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Stephanie B. Wall ◽  
Rachael Wood ◽  
Katelyn Dunigan ◽  
Qian Li ◽  
Rui Li ◽  
...  
Keyword(s):  
Lung Injury ◽  
Thioredoxin Reductase ◽  
Antioxidant Defenses ◽  
Mrna Levels ◽  
Newborn Mice ◽  
Antioxidant Responses ◽  
Thioredoxin Reductase 1 ◽  
Gpx Activity

Background. Aurothioglucose- (ATG-) mediated inhibition of thioredoxin reductase-1 (TXNRD1) improves alveolarization in experimental murine bronchopulmonary dysplasia (BPD). Glutathione (GSH) mediates susceptibility to neonatal and adult oxidative lung injury. We have previously shown that ATG attenuates hyperoxic lung injury and enhances glutathione- (GSH-) dependent antioxidant defenses in adult mice. Hypothesis. The present studies evaluated the effects of TXNRD1 inhibition on GSH-dependent antioxidant defenses in newborn mice in vivo and lung epithelia in vitro. Methods. Newborn mice received intraperitoneal ATG or saline prior to room air or 85% hyperoxia exposure. Glutamate-cysteine ligase (GCL) catalytic (Gclc) and modifier (Gclm) mRNA levels, total GSH levels, total GSH peroxidase (GPx) activity, and Gpx2 expression were determined in lung homogenates. In vitro, murine transformed club cells (mtCCs) were treated with the TXNRD1 inhibitor auranofin (AFN) or vehicle in the presence or absence of the GCL inhibitor buthionine sulfoximine (BSO). Results. In vivo, ATG enhanced hyperoxia-induced increases in Gclc mRNA levels, total GSH contents, and GPx activity. In vitro, AFN increased Gclm mRNA levels, intracellular and extracellular GSH levels, and GPx activity. BSO prevented AFN-induced increases in GSH levels. Conclusions. Our data are consistent with a model in which TXNRD1 inhibition augments hyperoxia-induced GSH-dependent antioxidant responses in neonatal mice. Discrepancies between in vivo and in vitro results highlight the need for methodologies that permit accurate assessments of the GSH system at the single-cell level.

scholarly journals T-2 Toxin Induces Epiphyseal Plate Lesions via Decreased SECISBP2-Mediated Selenoprotein Expression in DA Rats, Exacerbated by Selenium Deficiency

Cartilage ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Jian Sun ◽  
Zixin Min ◽  
Wenxiang Zhao ◽  
Safdar Hussain ◽  
Yitong Zhao ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Selenium Deficiency ◽  
Cartilage Degradation ◽  
Epiphyseal Plate ◽  
Dark Agouti ◽  
Deficient Diet ◽  
Metabolic Imbalance ◽  
Se Deficiency ◽  
Matrix Metabolism ◽  
T2 Toxin

Objective Both selenium (Se) deficiency and mycotoxin T2 lead to epiphyseal plate lesions, similar to Kashin-Beck disease (KBD). However, regulation of selenoproteins synthesis mediated by SECISBP2, in response to these 2 environmental factors, remained unclear. The present study proposed to explore the mechanism behind the cartilage degradation resulting from Se deficiency and mycotoxin T2 exposure. Design Deep chondrocyte necrosis and epiphyseal plate lesions were replicated in Dark Agouti (DA) rats by feeding them T2 toxin/Se deficiency artificial synthetic diet for 2 months. Results Se deficiency led to decreased expression of COL2α1, while T2 treatment reduced the heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) expression, both of which affected the cartilage extracellular matrix metabolism in the rat models. The expression of Col2α1, Acan, Hs6st2, Secisbp2, Gpx1, and Gpx4 were all significantly decreased in cartilage tissues from DA rats, fed a Se-deficient diet or exposed to T2 toxin, contrary to Adamts4, whose expression was increased in both conditions. In addition, T2 treatment led to the decreased expression of SBP2, GPX1, GPX4, and total GPXs activity in C28/I2 cells. Conclusion DA rats exposed to T2 toxin and/or Se-deficient conditions serve as the perfect model of KBD. The 2 environmental risk factors of KBD, which serve as a “double whammy,” can intensify the extracellular matrix metabolic imbalance and the antioxidant activity of chondrocytes, leading to articular cartilage degradation and epiphyseal plate abnormalities similar to those observed in KBD.

scholarly journals Effect of selenium deficiency on hepatic lipid and lipoprotein metabolism in the rat

1997 ◽  
Vol 78 (3) ◽  
pp. 493-500 ◽  
Author(s):  
F. Nassir ◽  
C. Moundras ◽  
D. Bayle ◽  
C. Sérougne ◽  
E. Gueux ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Liver Microsomes ◽  
Ldl Receptor ◽  
Selenium Deficiency ◽  
Cholesterol Concentration ◽  
Deficient Diet ◽  
Hmg Coa Reductase ◽  
Hepatic Lipid ◽  
Se Deficiency ◽  
Coa Reductase

Since experimental Se deficiency results in a significant increase in plasma cholesterol concentration the present investigation was undertaken to assess further the influence of this deficiency on the expression of proteins involved in hepatic lipid metabolism. Se deficiency was induced by feeding weanling male Wistar rats on a deficient diet for 6 weeks. Hypercholesterolaemia associated with Se deficiency was related to increased 3-hydroxy-3-methylglutaryl-coA (HMG-CoA) reductase (EC 1.1.1.34) activity in liver microsomes as compared with control animals. Hepatic lipoprotein receptor levels (LDL-receptor and HDL-binding proteins, HB1 and HB2) were not significantly affected by Se deficiency, as assessed by immunoblotting. Plasma triacylglycerol concentrations tended to decrease in Se-deficient rats in concert with their reduced post-Triton secretion. There was no significant effect of Se deficiency on the hepatic synthesis of apolipoproteins. These results point to the need for further investigations into the mechanism related to the increased activity of HMG-CoA reductase and the enhanced cholesterogenesis in the liver of Se-deficient rats likely to result from this.Selenium: Cholesterol: Triacylglycerol: HMG-CoA reductase

scholarly journals Effects of Dietary Selenium Deficiency or Excess on Selenoprotein Gene Expression in the Spleen Tissue of Pigs

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1122 ◽  
Author(s):  
Zhuang Lu ◽  
Pengzu Wang ◽  
Teng Teng ◽  
Baoming Shi ◽  
Anshan Shan ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Type I ◽  
Mrna Levels ◽  
Spleen Tissue ◽  
Selenoprotein K ◽  
Selenoprotein Genes ◽  
Se Deficiency ◽  
Selenoprotein M

To evaluate the effects of dietary Se deficiency and excess on the mRNA levels of selenoproteins in pig spleen tissues, 20 healthy uncastrated boars (Duroc × Landrace × Yorkshire, 10 ± 0.72 kg) were randomly divided into four groups (5 pigs per group). The pigs were fed a Se deficient corn-soybean basal feed (Se content <0.03 mg/kg) or basal feed with added sodium selenite at 0.3, 1.0, or 3.0 mg Se/kg diet, respectively. The experiment lasted 16 weeks. The spleen tissue was collected to examine the mRNA expression levels of 24 selenoprotein genes at the end of the study. Compared with pigs in other groups, those fed with the 1.0 mg Se/kg diet had higher mRNA levels of glutathione peroxidase 1 (Gpx1), glutathione peroxidase 2 (Gpx2), deiodinase type II (Dio2), thioredoxin reductase 3 (Txnrd3), selenoprotein H (Selh), selenoprotein N, 1 (Sepn1), selenoprotein P1 (Sepp1), and selenoprotein V (Selv) in the spleen (p < 0.05). Dietary Se deficiency resulted in lower mRNA levels of Gpx1, Gpx2, glutathione peroxidase 3 (Gpx3), Dio2, thioredoxin reductase 2 (Txnrd2), Txnrd3, Selh, selenoprotein I (Seli), selenoprotein K (Selk), selenoprotein M (Selm), Sepn1, Sepp1, and Selv in the spleen than the other three groups. Dietary Se levels did not affect the mRNA levels of glutathione peroxidase 4 (Gpx4), deiodinase type I (Dio1), deiodinase type III (Dio3), selenophosphate synthetase 2 (Sephs2), thioredoxin reductase 1 (Txnrd1), selenoprotein O (Selo), selenoprotein S (Sels), selenoprotein W (Selw), selenoprotein X (Selx), and selenoprotein 15 (Sel15) in the spleen (p > 0.05). Dietary Se levels can affect the transcription levels of 14 selenoprotein genes in the spleen of pigs.

scholarly journals Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells

2006 ◽  
Vol 394 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Wendy L. Trigona ◽  
Isis K. Mullarky ◽  
Yuzhang Cao ◽  
Lorraine M. Sordillo
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Oxidant Stress ◽  
Thioredoxin Reductase ◽  
Aortic Endothelial Cells ◽  
Glutathione Peroxidase 1 ◽  
Thioredoxin Reductase 1 ◽  
Haem Oxygenase ◽  
Se Deficiency ◽  
Aortic Endothelial

Certain selenoproteins such as GPX-1 (glutathione peroxidase-1) and TrxR1 (thioredoxin reductase-1) possess important antioxidant defence functions in vascular endothelial cells. Reduced selenoprotein activity during dietary selenium (Se) deficiency can result in a compensatory increase of other non-Se-dependent antioxidants, such as HO-1 (haem oxygenase-1) that may help to counteract the damaging effects of oxidant stress. However, the role of individual selenoproteins in regulating vascular-derived protective gene responses such as HO-1 is less understood. Using an oxidant stress model based on Se deficiency in BAECs (bovine aortic endothelial cells), we sought to determine whether TrxR1 activity may contribute to the differential regulation of HO-1 expression as a function of altered redox environment. Se-sufficient BAECs up-regulated HO-1 expression following stimulation with the pro-oxidant, 15-HPETE (15-hydroperoxyeicosatetraenoic acid), and levels of this antioxidant inversely correlated with EC apoptosis. While Se-deficient BAECs exhibited higher basal levels of HO-1, it was not up-regulated upon 15-HPETE treatment, which resulted in significantly higher levels of pro-apoptotic markers. Subsequent results showed that HO-1 induction depended on the activity of TrxR1, as proved with chemical inhibitor studies and direct inhibition with TrxR1 siRNA. Finally, restoring intracellular levels of the reduced substrate Trx (thioredoxin) in Sedeficient BAECs was sufficient to increase HO-1 activation following 15-HPETE stimulation. These data provide evidence for the involvement of the Trx/TrxR system, in the regulation of HO-1 expression in BAECs during pro-oxidant challenge.

scholarly journals The Impact of Selenium Deficiency on Cardiovascular Function

2021 ◽  
Vol 22 (19) ◽  
pp. 10713
Author(s):  
Briana K. Shimada ◽  
Naghum Alfulaij ◽  
Lucia A. Seale
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Redox Regulation ◽  
Cardiovascular Health ◽  
Selenium Deficiency ◽  
Cardiovascular Function ◽  
Calcium Flux ◽  
Thyroid Hormone Metabolism ◽  
Se Deficiency ◽  
The Impact

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan’s Disease, an endemic disease characterized by cardiomyopathy and heart failure. Since then, Se deficiency has been associated with multiple cardiovascular diseases, including myocardial infarction, heart failure, coronary heart disease, and atherosclerosis. Se, through its incorporation into selenoproteins, is vital to maintain optimal cardiovascular health, as selenoproteins are involved in numerous crucial processes, including oxidative stress, redox regulation, thyroid hormone metabolism, and calcium flux, and inadequate Se may disrupt these processes. The present review aims to highlight the importance of Se in cardiovascular health, provide updated information on specific selenoproteins that are prominent for proper cardiovascular function, including how these proteins interact with microRNAs, and discuss the possibility of Se as a potential complemental therapy for prevention or treatment of cardiovascular disease.

scholarly journals Selenium Deficiency—From Soil to Thyroid Cancer

2020 ◽  
Vol 10 (15) ◽  
pp. 5368
Author(s):  
Latifa Sarra Kazi Tani ◽  
Nouria Dennouni-Medjati ◽  
Benoit Toubhans ◽  
Laurent Charlet
Keyword(s):  
Thyroid Cancer ◽  
Antioxidant Defense ◽  
Redox Homeostasis ◽  
Selenium Deficiency ◽  
Strongly Correlated ◽  
Hormone Metabolism ◽  
Human Diet ◽  
Adverse Health Effects ◽  
Se Deficiency ◽  
The Impact

Selenium (Se) is an essential micronutrient present in human diet, entering in the composition of selenoproteins as selenocysteine (Se-Cys) amino acid. At the thyroid level, these proteins play an important role as antioxidant and in hormone metabolism. Selenoproteins are essential for the balance of redox homeostasis and antioxidant defense of mammalian organisms, while the corresponding imbalance is now recognized as the cause of many diseases including cancer. The food chain is the main source of Se in human body. Dietary intake is strongly correlated with Se content in soil and varies according to several factors such as geology and atmospheric input. Both Se deficiency and toxicity have been associated with adverse health effects. This review synthesizes recent data on the transfer of Se from soil to humans, Se U-shaped deficiency and toxicity uptake effects and particularly the impact of Se deficiency on thyroid cancer.

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