Knockout of Selenoprotein V Affects Regulation of Selenoprotein Expression by Dietary Selenium and Fat Intakes in Mice.

BACKGROUND: The metabolic function of selenoprotein V (SELENOV) remains unknown. OBJECTIVES: Two experiments were conducted to determine effects of the Selenov knockout (KO) on selenium concentration and mRNA, protein, and/or activity of 4 major selenoproteins [glutathione peroxidase (GPX) 1, GPX4, thioredoxin reductase-1 (TXNRD1), and selenoprotein P (SELENOP)] in the serum, liver, testis, and/or white adipose tissue (WAT) of mice fed different dietary selenium and fat concentrations. METHODS: In Experiment (Expt) 1, 40 KO and 40 wild-type (WT) mice (males, 8 wk old) were fed (n = 10/genotype) a casein-sucrose basal diet plus 0, 0.3, 1, or 3 mg Se/kg (as sodium selenite) for 32 wk . In Expt 2, 20 KO and 20 WT mice (males, 8 wk old) were fed (n  = 10/genotype) a normal-fat diet (NF; 10% calories from fat) or a high-fat diet (HF; 60% calories from fat) for 19 wk. RESULTS: In Expt 1, the KO caused consistent or substantial decreases (P < 0.05) of mRNA amounts of Gpx1, Txnrd1, and Selenop in the testis (≤52%), but selenium concentrations (19-29%) and GPX activities (≤ 50%) were decreased in the liver across different dietary selenium concentrations . Hepatic and testis GPX1 protein was elevated (≤31%) and decreased (≤45%) by the KO, respectively. In Expt 2, the genotype and dietary fat intake exerted interaction effects ( P < 0.05) on Gpx1 mRNA amounts in the WAT; Gpx1, Txnrd1, and Selenop mRNA amounts and TXNRD activities in the testis; and selenium concentrations in the serum and liver. However, these 2 treatments produced largely independent or additive effects (P < 0.05) on the GPX1 and SELENOP protein amounts in the liver and testis (up to ± 50% changes). CONCLUSIONS: The KO-mediated changes in the tissue selenium concentrations and functional expression of 3 major selenoproteins implied potential for SELENOV in regulating body selenium metabolism in the mouse.

Organophosphorus pesticide triazophos: A new endocrine disruptor chemical of hypothalamus-pituitary-adrenal axis.

The organophosphorus pesticide, triazophos (TAP) was banned to use in agriculture in several countries due to its high toxicity. However, TAP was still widely used and frequently detected in foods. Recently, many studies reported the endocrine-disrupting effect of pesticides, especially the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis. In this study, adult male Wistar rats were exposed to TAP at the dose of 0.164 and 1.64 mg/kg bodyweight (~1/500th and 1/50th of LD50) for 24 weeks and serum contents of hormones were measured. TAP exposure significantly reduced serum contents of adrenocorticotropic hormone, corticosterone and epinephrine in rats (p < .05), leading to the delay in glucose homeostasis during the insulin tolerance test and decrease in serum contents of total cholesterol, triglyceride and low density lipoprotein. Molecular docking results suggested TAP may be an antagonist of glucocorticoid receptor which decreased significantly in the liver of rats, resulting in the decreased expression of 11ß-hydroxysteroid dehydrogenase 1 and PEPCK1. This study revealed that TAP is a potential endocrine disruptor, especially in the hypothalamus-pituitary-adrenal system and may disturb the metabolism by affecting glucocorticoid receptor. This study provided new evidence about the toxicity of TAP and it was necessary to strictly control the usage of TAP in food.

Characterization of Selenoprotein M and Its Response to Selenium Deficiency in Chicken Brain.

Selenoprotein M (SelM) may function as thiol disulfide oxidoreductase that participates in the formation of disulfide bonds and can be implicated in calcium responses. SelM may have a functional role in catalyzing free radicals and has been associated with Alzheimer's disease (AD). However, studies of SelM in chicken remain very limited. In this study, two groups of day-old broiler chicks (n = 40/group) were fed a corn-soy basal diet (BD, 13 µg Se/kg) and BD supplemented with Se (as sodium selenite) at 0.3 mg/kg. The brain was collected at 14, 21, 28, and 42 days of age. We performed a sequence analysis and predicted the structure and function of SelM. We also investigated the effects of Se deficiency on the expression of Selt, Selw, and Selm and the Se status in the chicken brain. The results show that Se deficiency induced the lower (P < 0.05) Se content, glutathione peroxidase (GPx), and catalase (CAT) activities; increased (P < 0.05) malondialdehyde (MDA) content; and reduced (P < 0.05) the expression of Selm messenger RNA (mRNA) and protein abundance of SelM in the brain. However, there were no significant brain Selt and Selw mRNA levels by dietary Se deficiency in chicks. The different regulations of these three redox (Rdx) protein expressions by Se deficiency represent a novel finding of the present study. Our results demonstrated that SelM may have an important role in protecting against oxidative damage in the brain of chicken, which might shed light on the role of SelM in human neurodegenerative disease. More studies are needed to confirm our conclusion.

Selenoproteins protect against avian nutritional muscular dystrophy by metabolizing peroxides and regulating redox/apoptotic signaling.

Nutritional muscular dystrophy (NMD) of chicks is induced by dietary selenium (Se)/vitamin E (Vit. E) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms related to the presumed oxidative cell damage, we fed four groups of 1-day-old broiler chicks (n = 40/group) with a basal diet (BD; 10 µg Se/kg; no Vit. E added, -Se -Vit. E) or the BD plus all-rac-α-tocopheryl acetate at 50mg/kg (-Se +Vit. E), Se (as sodium selenite) at 0.3mg/kg (+Se -Vit. E), or both of these nutrients (+Se +Vit. E) for 6 weeks. High incidences of NMD (93%) and mortality (36%) of the chicks were induced by the BD, starting at week 3. Dietary Se deficiency alone also induced muscle fiber rupture and coagulation necrosis in the pectoral muscle of chicks at week 3 and thereafter, with increased (P < 0.05) malondialdehyde, decreased (P < 0.05) total antioxidant capacity, and diminished (P < 0.05) glutathione peroxidase activities in the muscle. To link these oxidative damages of the muscle cells to the Se-deficiency-induced NMD, we first determined gene expression of the potential 26 selenoproteins in the muscle of the chicks at week 2 before the onset of symptoms. Compared with the +Se chicks, the -Se chicks had lower (P < 0.05) muscle mRNA levels of Gpx1, Gpx3, Gpx4, Sepp1, Selo, Selk, Selu, Selh, Selm, Sepw1, and Sep15. The -Se chicks also had decreased (P < 0.05) production of 6 selenoproteins (long-form selenoprotein P (SelP-L), GPx1, GPx4, Sep15, SelW, and SelN), but increased levels (P < 0.05) of the short-form selenoprotein P in muscle at weeks 2 and 4. Dietary Se deficiency elevated (P < 0.05) muscle p53, cleaved caspase 3, cleaved caspase 9, cyclooxygenase 2 (COX2), focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), phospho-Akt, nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, phospho-JNK, and phospho-ERK and decreased (P < 0.05) muscle procaspase 3, procaspase 9, and NF-κB inhibitor α. In conclusion, the downregulation of SelP-L, GPx1, GPx4, Sep15, SelW, and SelN by dietary Se deficiency might account for induced oxidative stress and the subsequent peroxidative damage of chick muscle cells via the activation of the p53/caspase 9/caspase 3, COX2/FAK/PI3K/Akt/NF-κB, and p38 MAPK/JNK/ERK signaling pathways. Metabolism of peroxides and redox regulation are likely to be the mechanisms whereby these selenoproteins prevented the onset of NMD in chicks.

Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks.

Dietary selenium (Se) deficiency causes muscular dystrophy in various species, but the molecular mechanism remains unclear. Our objectives were to investigate: 1) if dietary Se deficiency induced different amounts of oxidative stress, lipid peroxidation, and cell apoptosis in 3 skeletal muscles; and 2) if the distribution and expression of 4 endoplasmic reticulum (ER) resident selenoprotein genes (Sepn1, Selk, Sels, and Selt) were related to oxidative damages in these muscles. Two groups of day-old layer chicks (n = 60/group) were fed a corn-soy basal diet (33 µg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or the diet supplemented with Se (as sodium selenite) at 0.15 mg/kg for 55 d. Dietary Se deficiency resulted in accelerated (P < 0.05) cell apoptosis that was associated with decreased glutathione peroxidase activity and elevated lipid peroxidation in these muscles. All these responses were stronger in the pectoral muscle than in the thigh and wing muscles (P < 0.05). Relative distribution of the 4 ER resident selenoprotein gene mRNA amounts and their responses to dietary Se deficiency were consistent with the resultant oxidative stress and cell apoptosis in the 3 muscles. Expression of Sepn1, Sels, and Selt in these muscles was correlated with (r > 0.72; P < 0.05) that of Sepsecs encoding a key enzyme for biosynthesis of selenocysteine (selenocysteinyl-tRNA synthase). In conclusion, the pectoral muscle demonstrated unique expression patterns of the ER resident selenoprotein genes and GPx activity, along with elevated susceptibility to oxidative cell death, compared with the other skeletal muscles. These features might help explain why it is a primary target of Se deficiency diseases in chicks.

Orally administered Dendrobium officinale and its polysaccharides enhance immune functions in BALB/c mice.

The immunoactivity was evaluated of Dendrobium officinale Kimura & Migo, a Chinese herbal plant, and its crude polysaccharides. Different dosages of D. officinale and its polysaccharides were orally administered to healthy BALB/c mice. The control group was given distilled water. After 4 weeks, immune parameters, including cellular immunity (delayed-type hypersensitivity and natural killer cell activity), humoral immunity (serum hemolytic complement activity), nonspecific immunity (peritoneal macrophage phagocytosis) and interferon-gamma production by splenocytes were measured. The results showed that D. officinale and its polysaccharides can significantly enhance cellular immunity and nonspecific immunity in mice. Humoral immunity was also enhanced after oral administration of D. officinale, but the polysaccharides had no influence. Both D. officinale and its polysaccharides markedly increased IFN-gamma production by murine splenocytes. Six fractions were isolated from the polysaccharides; the molecular weight of the major fraction was 533,700 Da, and composed of mannose, glucose and rhamnose in a molar ratio of 7.3:1.3:1.0.

[Study of microstructure of pectin and whey protein isolate mixtures under incompatible conditions using dynamic light scattering and transmission electron microscopy].

The microstructure of the pectin/whey protein isolate mixtures under incompatible conditions was investigated using dynamic light scattering spectroscopy, transmission electron microscopy and shear-viscosity model. Under the condition of 90 degrees C and pH 7.4, the presence of negatively charged pectin could induce depletion aggregation in a 5% protein solution, and promote phase separation; precisely, when the mass ratio of pectin/whey protein isolate was lower than 0.08, the hydrodynamic size of the aggregates was less than 300 nm, and the system showed Newtonian properties; when the mass ratio was higher than 0.08, the viscosity of the solution increased rapidly, the shear thinning properties became obvious and the size of the aggregates was close to 700 nm.