Effects of Different Selenium Levels on Gene Expression of a Subset of Selenoproteins and Antioxidative Capacity in Mice

Biological Trace Element Research, Jun 2013

This study aimed to evaluate how excess selenium induces oxidative stress by determining antioxidant enzyme activity and changes in expression of selected selenoproteins in mice. BALB/c mice (n = 20 per group) were fed a diet containing 0.045 (Se-marginal), 0.1 (Se-adequate), 0.4 (Se-supernutrition), or 0.8 (Se-excess) mg Se/kg. Gene expression was quantified in RNA samples extracted from the liver, kidney, and testis by real-time quantitative reverse transcription-polymerase chain reaction. We found that glutathione peroxidase (GPx) and catalase activities decreased in livers of mice fed the marginal or excess dose of Se as compared to those in the Se-adequate group. Additionally, superoxide dismutase and glutathione reductase activities were significantly reduced only in mice fed the excess Se diet, compared to animals on the adequate Se diet. Se-supernutrition had no effect on hepatic mRNA levels of GPx isoforms 1 and 4 (GPx1 and GPx4), down-regulated GPx isoform 3 (GPx3), and upregulated selenoprotein W (SelW) mRNA expression. The excess Se diet led to decreased hepatic mRNA levels of GPx1, GPx3 and GPx4 but no change in testicular mRNA levels of GPx1, GPx3 or SelW. Dietary Se had no effect on testicular mRNA levels of GPx4. Thus, our results suggest that Se exposure can reduce hepatic antioxidant capacity and cause liver dysfunction. Dietary Se was found to differentially regulate mRNA levels of the GPx family or SelW, depending on exposure. Therefore, these genes may play a role in the toxicity associated with Se.

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Effects of Different Selenium Levels on Gene Expression of a Subset of Selenoproteins and Antioxidative Capacity in Mice

Qin Zhang 0 Long Chen 0 Kai Guo 0 Liangyan Zheng 0 Bitao Liu 0 Wenlan Yu 0 Cuili Guo 0 Zhengwei Liu 0 Ye Chen 0 Zhaoxin Tang 0 0 Qin Zhang, Long Chen, Kai Guo, and Zhaoxin Tang contributed equally to this work 1 ) College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642, China This study aimed to evaluate how excess selenium induces oxidative stress by determining antioxidant enzyme activity and changes in expression of selected selenoproteins in mice. BALB/c mice (n =20 per group) were fed a diet containing 0.045 (Se-marginal), 0.1 (Seadequate), 0.4 (Se-supernutrition), or 0.8 (Se-excess) mg Se/kg. Gene expression was quantified in RNA samples extracted from the liver, kidney, and testis by real-time quantitative reverse transcription-polymerase chain reaction. We found that glutathione peroxidase (GPx) and catalase activities decreased in livers of mice fed the marginal or excess dose of Se as compared to those in the Se-adequate group. Additionally, superoxide dismutase and glutathione reductase activities were significantly reduced only in mice fed the excess Se diet, compared to animals on the adequate Se diet. Se-supernutrition had no effect on hepatic mRNA levels of GPx isoforms 1 and 4 (GPx1 and GPx4), downregulated GPx isoform 3 (GPx3), and upregulated selenoprotein W (SelW) mRNA expression. The excess Se diet led to decreased hepatic mRNA levels of GPx1, GPx3 and GPx4 but no change in testicular mRNA levels of GPx1, GPx3 or SelW. Dietary Se had no effect on testicular mRNA levels of GPx4. Thus, our results suggest that Se exposure can reduce hepatic antioxidant capacity and cause liver dysfunction. Dietary Se was found to differentially regulate mRNA levels of the GPx family or SelW, depending on exposure. Therefore, these genes may play a role in the toxicity associated with Se. - Selenium (Se) is an essential nutritional trace element, which is best known for its antioxidant properties that are mediated by various selenoproteins. At least 25 selenoproteins in humans and 24 homologues in rodents have been identified [1]. They play important roles in diverse physiological processes such as chemoprevention, neurobiology, aging, immunity (i.e., immune responses, anti-inflammatory activity and antiviral activity), muscle metabolism, reproduction, and redox reactions [2]. The synthesis of selenoproteins is affected by levels of Se supplementation. Broadly, the field of biological Se research can be divided into two distinct areas: study of the Se nutritional essentiality and study of Se toxicity [3]. Both excessive and insufficient Se intake can result in adverse health effects [47]. There are numerous reports regarding the effects of Se deficiency. Gastrointestinal glutathione peroxidase (GI-GPx/GPx2) mRNA increases in Sedeficient mice [8], whereas GPx isoform 4 (GPx4) mRNA decreases substantially in Se-deficient turkey liver [9]. The levels of GPx isoform 1 (GPx1), selenoprotein W (SelW), and selenoprotein H (SelH) are dramatically decreased in Se-deficient, compared to Se-replete, rats [10]. Severe Se deficiency causes almost total loss of GPx1 activity and mRNA in the rat liver and heart, while GPx4 activity is reduced by 75 % in the liver and 60 % in the heart, leaving mRNA levels unchanged [6]. Liver Se concentration and liver GPx1 and thioredoxin reductase (Txnrd) activities were reduced in Se-deficient mice compared to Seadequate mice [11]. Several groups have also examined the effects of excess Se intake. At high concentrations, selenite is known to induce apoptosis in cells by a mechanism involving free radicals [12]. Further, Se and GPx levels are increased in animals treated with an excess of Se [13]. GPx mRNA levels and activities were significantly increased in rats injected with 20 mg Se/kg per day, but dramatically decreased upon injection of 40 or 80 mg Se/kg per day [4]. GPx4 mRNA level in chicken was down-regulated by an excess of Se [14]. When dietary Se is increased from 0.3 to 3.0 mg Se/kg, testicular mRNA levels of Txnrd1 and selenoprotein 15 (Sep15) are attenuated, whereas expression of Gpx1 is increased in the pig liver [15]. A significant decrease in total superoxide dismutase (SOD) activity has been reported in animals with both excess and depleted Se [16]. The above results show that Se supplementation in animals has been extensively studied. There is evidence to suggest that excess selenite and selenomethionine [17, 18] can impair the amount and/or activity of biological antioxidant defense mechanisms by generation of oxygen-free radicals [19]. The Nutritional Prevention of Cancer Trial found that Se supplementation increased the risk of squamous cell carcinoma, total cancer incidence, and diabetes in subjects with higher plasma Se levels [20]. Despite this, little information is available on the effects of Se overexposure on GPx and SelW1 gene expression in mice. Examining the modulation of selenoprotein expression upon Se exposure m (...truncated)


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Qin Zhang, Long Chen, Kai Guo, Liangyan Zheng, Bitao Liu, Wenlan Yu, Cuili Guo, Zhengwei Liu, Ye Chen, Zhaoxin Tang. Effects of Different Selenium Levels on Gene Expression of a Subset of Selenoproteins and Antioxidative Capacity in Mice, Biological Trace Element Research, 2013, pp. 255-261, Volume 154, Issue 2, DOI: 10.1007/s12011-013-9710-z