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)