硒蛋白P的研究进展

硒蛋白P（SeP)是从大鼠和人血浆中分离,纯化得到的一种糖蛋白,每个硒蛋白P多肽含有10个硒代半胱氨酸,硒蛋白P中的硒含量占大鼠和人血浆中硒含量的50%以上,在其mRNA开放阅读框架中克隆的cDNA的序列含有10个UGA密码子。硒代半胱氨酸在一个UGA密码子处嵌入蛋白的一级结构,尽管对硒蛋白P功能还没有彻底了解,它的一种非常可能的作用是作为一种胞外抗氧化剂,大鼠血浆中的硒蛋白P在体内实验中对Diquat诱导的脂质过氧化和肝损坏具有保护作用,人血浆中的硒蛋白P在体外实验中显示减少内作为一存活促进因子。     

硒蛋白P的研究进展

硒蛋白P(SeP)是从大鼠和人血浆中分离、纯化得到的一种糖蛋白 ,每个硒蛋白P多肽含有10个硒代半胱氨酸。硒蛋白P中的硒含量占大鼠和人血浆中硒含量的 5 0 %以上。在其mRNA开放阅读框架中克隆的cDNA的序列含有 10个UGA密码子。硒代半胱氨酸在一个UGA密码子处嵌入蛋白的一级结构 ,尽管对硒蛋白P功能还没有彻底了解 ,它的一种非常可能的作用是作为一种胞外抗氧化剂。大鼠血浆中的硒蛋白P在体内实验中对Diquat诱导的脂质过氧化和肝损坏具有保护作用 ,人血浆中的硒蛋白P在体外实验中显示减少内毒素过氧化硝酸盐和磷脂氢过氧化物的活性。牛血浆中的硒蛋白P在神经细胞的培养中作为一存活促进因子。     

硒蛋白P的研究进展

微量元素硒 (Ｓｅ)作为许多具有重要生物功能的硒酶的活性中心 ,不但与机体的免疫应答及抗氧化作用等生理功能密切相关 ,而且能够降低癌症的发生率[1,2 ] 。在流行病学和临床研究中 ,常用血浆或全血中Ｓｅ浓度作为衡量Ｓｅ状态的指标 ,而且血浆浓度能比全血浓度更迅速地反映Ｓｅ状态的变化。在哺乳动物血浆中 ,Ｓｅ主要结合在 3种蛋白质中 :硒蛋白Ｐ、胞外谷胱甘肽过氧化物酶和清蛋白。其中硒蛋白Ｐ所含Ｓｅ大约占血浆中全部Ｓｅ浓度的 5 0 %。硒蛋白Ｐ不同于目前所鉴定的所有其他硒蛋白 ,因为它含有 10～ 12个硒代半胱氨酸 (ＳｅＣｙｓ)残…     

硒蛋白的分子生物学研究进展

已有35种硒蛋白被分离和表征,但许多硒蛋白及其功能仍未完全阐明.硒半胱氨酸(Sec)作为参入蛋白质的第21种氨基酸,由硒蛋白mRNA上的UGA编码.在原核生物,Sec参入硒蛋白的复杂机制已经较为明确,需要四种基因产物（SELA、SELB、SELC和SELD）和一个存在于硒蛋白mRNA上的被称为Sec插入序列(SECIS)的茎环(stem loop)样二级结构.在真核生物,硒蛋白生物合成途径可能在SECIS的结构和位置、特异的延伸因子及其他RNA-RNA或RNA-蛋白质因子之间的相互作用等方面与原核生物不同.另外,哺乳动物硒蛋白mRNA上的UGA翻译为Sec的过程低效,特定位点的UGA密码子不同功能(终止密码和Sec密码)的调控可能是硒蛋白表达低效的关键.     

生物合成硒蛋白机制的研究进展

作为第 2 1种氨基酸 ,硒代半胱氨酸在翻译阶段由核糖体介导 ,在mRNA编码区的UGA密码子处参入多肽链。研究表明硒代半胱氨酸的参入需要一个顺式作用元件SECIS和 4个基因产物 :SelA、SelB、SelC、SelD。原核生物和真核生物的SECIS在mRNA中的位置和结构特征差异显著。在利用Escherichiacoli硒代半胱氨酸的参入机制合成硒蛋白方面 ,研究人员进行了有益的探索。     

硒蛋白

硒(Se)已被确认为是一种生物微量元素,它能共价结合到生物大分子、尤其是蛋白质中。硒蛋白是某些细菌、鸟类、哺乳动物(可能也包含植物)的酶系统的基本成份。一、细菌硒蛋白最早被鉴定的细菌硒蛋白是依赖硒的甲酸脱氢酶,该酶催化无氧条件下HCOOH?H_2+CO_2。Pinsent(954)指出,E·Coli甲酸脱氢酶的表达需要硒。Lester和Demoss(1971)则     

硒蛋白P的研究进展

硒蛋白P最初在血浆中发现,占血浆总硒的60%,在其多肽链中有10个硒半胱氨酸。由10个读码框内的UGA编码,而UGA一般是作为终止密码子起作用,故硒蛋白P的生物合成需要多个特异的因子。如特异的tR-NA,延伸因子和mRNA上的特异的二级结构等。硒蛋白P的功能尚不清,初步的研究结果提示可有转运硒,抗氧化,结构重金属和神经营养等作用。     

利用哺乳动物细胞表达外源蛋白的研究进展

利用哺乳动物细胞表达外源蛋白已广泛应用于生物产品的制备,哺乳动物细胞是表达具有天然活性蛋白的最佳宿主,且具有易被转染,遗传稳定,产物可分泌表达,并易于纯化和大规模生产等方面的优势。本文对选择载体类型,载体元件（包括启动子,增强子,选择标记等）以及在哺乳动物细胞大规模培养过程中培养环境,细胞凋亡的抑制和控制细胞增殖和基因表达的Tet-switch系统等方面的进展作一综述,以探讨提高该系统表达产量的有效方法,更好地应用于生物制品的生产。     

一种新的硒酶——硫氧还蛋白还原酶

必需微量元素硒的生物功能主要是通过各种硒酶和硒蛋白来实现的,如谷胱甘肽过氧化物酶（ＧＰｘ）类具有抗氧化功能,碘甲腺原氨酸脱碘酶（ＤＩ）类在甲状腺激素的生物合成和代谢中具有重要作用。已有研究表明,在哺乳动物各种组织中可能大约存在２５种左右硒蛋白,但是迄...     

植物硒及其含硒蛋白的研究

硒是植物的有益元素,植物对硒的吸收与外源硒的有效性、硒的形态、植物的种类等有关;硒在植物中主要以有机硒形态存在,HPLC-ICP-MS联用已成为植物体内硒形态鉴定的最常用手段;含硒蛋白是植物体内最主要的有机大分子硒,具有抗肿瘤、抗氧化等多种生物活性。在环境安全和人类健康等方面,富硒植物具有很好的应用价值,所以利用分子生物学手段分析富硒植物的富硒机制,可以为富硒基因的筛选和利用提供理论依据。     

Some properties of selenoprotein P

Selenoprotein P is a newly characterized selenoprotein. It is the first protein described to contain multiple selenocysteines. It is secreted by the liver into the plasma and turns over rapidly. Its concentration is sensitive to the selenium status of the animal. Its function is unknown.     

Dietary selenium deficiency and supplementation differentially modulate the expression of two ER-resident selenoproteins (selenoprotein K and selenoprotein M) in the ovaries of aged mice: Preliminary data

In the present report, we determined the impact of dietary selenium (Se) deficiency and supplementation on the expression of two ER-resident selenoproteins i.e., Selenok and Selenom in the ovaries of aging mice. The mRNA expression of Selenok and Selenom (RT-qPCR) was significantly higher in the ovaries of mice fed diets supplemented with inorganic (ISe-S: 0.33 mg Se/kg) and organic (OSe-S: 0.33 mg Se/kg) Se compared to those fed a Se-deficient (Se-D: 0.08 mg Se/kg) diet and both Se-adequate (ISe-A: 0.15 mg Se/kg and OSe-A: 0.15 mg Se/kg) diets. Similarly, the protein signals of SELENOK (immunofluorescence assay) were also significantly higher in the Se-supplemented groups compared to those fed Se-D and Se-adequate (ISe-A and OSe-A) diets. Meanwhile, the rate of in vitro-produced blastocysts developing from MII oocytes was also evaluated and it was revealed that this rate was significantly higher in the Se-supplemented mice compared to those fed a Se-D diet. Altogether, the dietary Se supplementation increased the expression of Selenok (also its protein expression) and Selenom in the ovaries of aging mice, potentially contributing to an improved developmental potential of in vitro-matured M II oocytes.     

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Selenium (Se), a dietary trace metal essential for human health, is incorporated into ~25 selenoproteins including selenoprotein S (SelS) and the 15-kDa selenoprotein (Sep15) both of which have functions in the endoplasmic reticulum protein unfolding response. The aim of this study was to investigate whether genetic variants in such selenoprotein genes are associated with altered risk of colorectal cancer (CRC). A Korean population of 827 patients with CRC and 733 healthy controls was genotyped for 7 SNPs in selenoprotein genes and one SNP in the gene encoding manganese superoxide dismutase using Sequenom technology. Multivariate logistic regression analysis showed that after adjustment for lifestyle factors three SNP variants were associated with altered disease risk. There was a mean odds ratio of 2.25 [95% CI 1.13,4.48] in females homozygous TT for rs34713741 in SELS with the T variant being associated with higher risk of rectal cancer, and odds ratios of 2.47 and 2.51, respectively, for rs5845 and rs5859 in SEP15 with the minor A and T alleles being associated with increased risk of male rectal cancer. The data indicate that the minor alleles for rs5845, rs5859 and rs34713741 are associated with increased rectal cancer risk and that the effects of the three SNPs are dependent on gender. The results highlight potential links between Se, the function of two selenoproteins involved in the protein unfolding response and CRC risk. Further studies are required to investigate whether the effects of the variants on CRC risk are also modulated by dietary Se intake.     

Serum selenium and selenoprotein P status in adult Danes – 8-year followup

Selenium is an essential micronutrient important to human health. The main objective of this study is to describe serum selenium and selenoprotein P status in two samples of the Danish population. In addition, the influence of various factors potentially associated with selenium status was investigated.Blood samples from a total of 817 randomly selected subjects from two cities in Denmark were analyzed. Half of the samples were collected in 1997–1998 and the other half in 2004–2005. Samples from women aged 18–22, 40–45 and 60–65 years, and men aged 60–65 years were selected for this study. All subjects had filled in a food frequency questionnaire (FFQ) and a questionnaire with information about smoking habits, alcohol consumption and exercise habits.Mean serum selenium level was 98.7±19.8 μg/L and median selenoprotein P level was 2.72 (2.18–3.49) mg/L. Serum selenium and selenoprotein P increased with age, and selenoprotein P was higher in men than in women. Serum selenium levels decreased by 5% on average from 1997–98 to 2004–05 (P<0.001), whereas selenoprotein P level increased (P<0.001). The intake of fish correlated weakly with serum selenium level (r=0.14, P<0.001) but not with selenoprotein P level. Smoking status, alcohol intake, exercise habits, BMI and medicine use did not influence selenium status.It is concluded that selenium status in this Danish population is at an acceptable level. No major groups with regard to age, sex or lifestyle factors could be identified as being in risk for selenium deficiency.     

Selenium prevents downregulation of antioxidant selenoprotein genes by methylmercury

Selenium (Se) is an essential nutrient required by Se-dependent proteins, termed selenoproteins. The selenoprotein family is small but diverse and includes key proteins in antioxidant, redox signaling, thyroid hormone metabolism, and protein folding pathways. Methylmercury (MeHg) is a toxic environmental contaminant that affects seafood safety. Selenium can reduce MeHg toxicity, but it is unclear how selenoproteins are affected in this interaction. In this study we explored how Se and MeHg interact to affect the mRNA expression of selenoprotein genes in whole zebrafish (Danio rerio) embryos. Embryos were obtained from adult zebrafish fed MeHg with or without elevated Se in a 2×2 factorial design. The embryo mRNA levels of 30 selenoprotein genes were then measured. These genes cover most of the selenoprotein families, including members of the glutathione peroxidase (GPX), thioredoxin reductase, iodothyronine deiodinase, and methionine sulfoxide reductase families, along with selenophosphate synthetase 2 and selenoproteins H, J-P, T, W, sep15, fep15, and fam213aa. GPX enzyme activity and larval locomotor activity were also measured. We found that around one-quarter of the selenoprotein genes were downregulated by elevated MeHg. These downregulated genes were dominated by selenoproteins from antioxidant pathways that are also susceptible to Se-deficiency-induced downregulation. MeHg also decreased GPX activity and induced larval hypoactivity. Elevated Se partially prevented MeHg-induced disruption of selenoprotein gene mRNA levels, GPX activity, and larval locomotor activity. Overall, the MeHg-induced downregulation and subsequent rescue by elevated Se levels of selenogenes regulated by Se status suggest that Se deficiency is a contributing factor to MeHg toxicity.     

Molecular mechanism of selenoprotein P synthesis

Background

Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated translation factors. Among the mammalian selenoproteins, Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.

A spatial study on serum selenoprotein P and Keshan disease in Heilongjiang Province,China

BackgroundFew spatial studies on serum selenoprotein P (SELENOP) and Keshan disease (KD) have been reported at the county-level in Heilongjiang province, China. This study aimed to provide visualized spatial epidemiological evidence of selenium molecular marker in residents living in endemic areas for the precise assessment of prevention, control, and elimination of KD.MethodsUsing a spatial ecological study design, 587 subjects living in cities, townships, and rural areas of 50 KD endemic counties and 37 non-endemic counties in Heilongjiang province were investigated. The serum SELENOP levels of the participants were measured by enzyme-linked immunosorbent assay. Thematic maps were created, and spatial regression analysis was conducted using ordinary least squares.ResultsThe mean serum SELENOP level of the 587 subjects was 7.4 ± 3.0 μg/mL. The mean levels of serum SELENOP were higher in cities (7.4 ± 2.9 μg/mL) and townships (7.9 ± 3.2 μg/mL) than in rural areas (6.0 ± 3.0 μg/mL). The mean levels of serum SELENOP were trending towards high levels in non-endemic areas (7.4 ± 3.0 μg/mL) than in KD endemic areas (6.3 ± 3.3 μg/mL). Spatial regression analysis showed that the serum SELENOP level was positively correlated with the per capita gross domestic product.ConclusionSelenium deficiency may still exist in some KD endemic counties in Heilongjiang province, including Lingdong, Nenjiang, and Baiquan; these counties should be considered as key areas for precision prevention, control, and elimination of KD. Inclusion of selenium in the national surveillance of KD will provide more evidence for the assessment of KD elimination from a selenium nutrition perspective.     

Umbilical cord blood and placental mercury,selenium and selenoprotein expression in relation to maternal fish consumption

Seafood is an important source of nutrients for fetal neurodevelopment. Most individuals are exposed to the toxic element mercury through seafood. Due to the neurotoxic effects of mercury, United States government agencies recommend no more than 340 g (12 oz) per week of seafood consumption during pregnancy. However, recent studies have shown that selenium, also abundant in seafood, can have protective effects against mercury toxicity. In this study, we analyzed mercury and selenium levels and selenoprotein mRNA, protein, and activity in placenta of a cohort of women in Hawaii in relation to maternal seafood consumption assessed with dietary surveys. Fish consumption resulted in differences in mercury levels in placenta and cord blood. When taken as a group, those who consumed no fish exhibited the lowest mercury levels in placenta and cord blood. However, there were numerous individuals who either had higher mercury with no fish consumption or lower mercury with high fish consumption, indicating a lack of correlation. Placental expression of selenoprotein mRNAs, proteins and enzyme activity was not statistically different in any region among the different dietary groups. While the absence of seafood consumption correlates with lower average placental and cord blood mercury levels, no strong correlations were seen between seafood consumption or its absence and the levels of either selenoproteins or selenoenzyme activity.