含硒酶与非酶作用机制

在微生物、植物和动物体内,硒的功能形式多种多样,但其作用机制可归纳为酶与非酶两个方面,含硒酶的作用主要有：谷胱甘肽过氧化物酶（GPx）家族催化超氧化物还原,防止细胞膜的氧化损伤;脱磺酶（ID）家族调节甲状腺激素代谢,硫氧还蛋白还原酶（TDR）家族催化硫氧还蛋白（Trx）还原,TDR／Trx系统为细胞的生长和分化所必需,硒的非酶化学保护作用体现在：可诱导一些蛋白激酶的富半胱氨酸结构域发生氧化还原修饰,增强免疫功能等作用,硒在植物中的作用机制具有许多特殊性。     

富硒酵母中硒赋态的研究

硒是人体必需的一种微量元素,参与合成硒代半胱氨酸、硒代甲硫氨酸以及多种硒代蛋白(酶),具有抗肿瘤、抗氧化、增强人体免疫等多种生物学活性,与人体的健康有着密切关系.硒以不同的形式存在于自然界中,大致可分为无机硒和有机硒两种,其生物活性与毒性也各有不同.富硒酵母作为补充硒元素的主要形式之一,具有生物利用度高、食用安全、毒性低等优点.研究富硒酵母中的硒的赋态,对合理摄取硒元素,促进人体健康具有重要意义,因此成为近年来研究的热点.     

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

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(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。     

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。     

疟蚊基因组中新硒蛋白的计算机识别

硒蛋白的生物合成取决于硒代半胱氨酸插入蛋白质的过程. TGA码既是终止码、又可翻译成硒代半胱氨酸, 这使普通基因注释软件无法正确预测硒蛋白, 导致现有数据库中许多物种的硒蛋白被错误注释或丢失. 本研究基于已公布的疟蚊基因组预测信息、采用PERL语言编程, 对疟蚊基因组中的硒蛋白进行了计算机检索与分析. 结果表明: 以TGA码终止的基因有11365条, 其中具有SECIS结构的基因有918条, 同时具有半胱氨酸同源类似物的基因58条. 再经Sec侧翼序列比对, 最终检索到具有硒蛋白全部特点的基因7条. 从硒蛋白的基本生物功能推测, 冈比亚疟蚊基因组中存在的新硒蛋白可能与疟蚊的氧化耐受特性及其相关蛋白的调控相关联. 因此, 研究疟蚊硒蛋白将为干涉疟蚊带菌能力、从蚊媒传播途径防止疟疾提供理论基础.     

哺乳动物硒蛋白的研究进展

硒是哺乳动物和人必需的微是元素。硒的生物学功能主要是以硒蛋白的形式表现的。到目前为止,已经克隆并测定ｃＤＮＡ顺序的哺乳动物硒蛋白有９种停,它们是细胞内谷胱甘肽过氧化物酶、细胞外谷胱甘肽过氧化物酶、磷脂氢谷胱甘肽过氧化物酶、胃肠谷胱甘肽过氧化物酶、Ｉ型碘化甲状腺原氨酸５′脱碘酶、Ⅱ型碘化甲状腺原氨酸５′脱磺酶、Ⅲ型碘化甲状腺原氨酸５′脱碘酶、硒蛋白Ｐ和硒蛋白Ｗ。这些硒蛋白中硒参入到蛋白分子是通过硒半     

硒的生物活性与相关疾病

微量元素硒对人类有重要的生物学意义,硒在机体内发挥功能的主要形式是硒蛋白,特别是硒酶,其主要生物活性包括:防止自由基损伤、调节甲状腺激素和二十碳花生四烯酸代谢、增强免疫、促进生殖等。研究表明,缺硒与许多疾病如心血管系统疾病、癌症、病毒感染等有关。含硒活性物质具有良好的营养保健及医药应用前景。     

Selenium and selenoproteins in prostanoid metabolism and immunity

Abstract

Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is associated with pathological conditions in humans and animals, where incorporation of Sec into selenoproteins is reduced along with their expression and catalytic activity. Supplementation of Se-deficient population with Se has shown health benefits suggesting the importance of Se in physiology. An interesting paradigm to explain, in part, the health benefits of Se stems from the observations that selenoprotein-dependent modulation of inflammation and efficient resolution of inflammation relies on mechanisms involving a group of bioactive lipid mediators, prostanoids, which orchestrate a concerted action toward maintenance and restoration of homeostatic immune responses. Such an effect involves the interaction of various immune cells with these lipid mediators where cellular redox gatekeeper functions of selenoproteins further aid in not only dampening inflammation, but also initiating an effective and active resolution process. Here we have summarized the current literature on the multifaceted roles of Se/selenoproteins in the regulation of these bioactive lipid mediators and their immunomodulatory effects.     

Evolution of selenocysteine-containing proteins: significance of identification and functional characterization of selenoproteins

In the genetic code, UGA serves as either a signal for termination or a codon for selenocysteine (Sec). Sec rarely occurs in protein and is different from other amino acids in that much of the biosynthetic machinery governing its incorporation into protein is unique to this amino acid. Sec-containing proteins have diverse functions and lack a common amino acid motif or consensus sequence. Sec has previously been considered to be a relic of the primordial genetic code that was counter-selected by the presence of oxygen in the atmosphere. In the present report, it is proposed that Sec was added to the already existing genetic code and its use has accumulated during evolution of eukaryotes culminating in vertebrates. The more recently evolved selenoproteins appear to take advantage of unique redox properties of Sec that are superior to those of Cys for specific biological functions. Further understanding of the evolution of selenoproteins as well as biological properties and biomedical applications of the trace element selenium requires identification and functional characterization of all mammalian selenoproteins.     

Altered protein expression pattern in colon tissue of mice upon supplementation with distinct selenium compounds

The essential trace element selenium (Se) is controversially discussed concerning its role in health and disease. Its various physiological functions are largely mediated by Se incorporation in the catalytic center of selenoproteins. In order to gain insights into the impact of Se deficiency and of supplementation with different Se compounds (selenite, selenate, selenomethionine) at defined concentrations (recommended, 150 μg/kg diet; excessive, 750 μg/kg diet) in murine colon tissues, a 20‐week feeding experiment was performed followed by analysis of the protein expression pattern of colon tissue specimens by 2D‐DIGE and MALDI‐TOF MS. Using this approach, 24 protein spots were identified to be significantly regulated by the different Se compounds. These included the antioxidant enzyme peroxiredoxin‐5 (PRDX5), proteins with binding capabilities, such as cofilin‐1 (COF1), calmodulin, and annexin A2 (ANXA2), and proteins involved in catalytic processes, such as 6‐phosphogluconate dehydrogenase (6PGD). Furthermore, the Se compounds demonstrated a differential impact on the expression of the identified proteins. Selected target structures were validated by qPCR and Western blot which mainly confirmed the proteomic profiling data. Thus, novel Se‐regulated proteins in colon tissues have been identified, which expand our understanding of the physiologic role of Se in colon tissue.     

Selenium and its' role in the maintenance of genomic stability

Selenium (Se) is an essential micronutrient for humans, acting as a component of the unusual amino acids, selenocysteine (Se-Cys) and selenomethionine (Se-Met). Where Se levels are low, the cell cannot synthesise selenoproteins, although some selenoproteins and some tissues are prioritised over others. Characterised functions of known selenoproteins, include selenium transport (selenoprotein P), antioxidant/redox properties (glutathione peroxidases (GPxs), thioredoxin reductases and selenoprotein P) and anti-inflammatory properties (selenoprotein S and GPx4). Various forms of Se are consumed as part of a normal diet, or as a dietary supplement. Supplementation of tissue culture media, animal or human diets with moderate levels of certain Se compounds may protect against the formation of DNA adducts, DNA or chromosome breakage, and chromosome gain or loss. Protective effects have also been shown on mitochondrial DNA, and on telomere length and function. Some of the effects of Se compounds on gene expression may relate to modulation of DNA methylation or inhibition of histone deacetylation. Despite a large number of positive effects of selenium and selenoproteins in various model systems, there have now been some human clinical trials that have shown adverse effects of Se supplementation, according to various endpoints. Too much Se is as harmful as too little, with animal models showing a "U"-shaped efficacy curve. Current recommended daily allowances differ among countries, but are generally based on the amount of Se necessary to saturate GPx enzymes. However, increasing evidence suggests that other enzymes may be more important than GPx for Se action, that optimal levels may depend upon the form of Se being ingested, and vary according to genotype. New paradigms, possibly involving nutrigenomic tools, will be necessary to optimise the forms and levels of Se desirable for maximum protection of genomic stability in all humans.     

The central role of selenium in the biochemistry and ecology of the harmful pelagophyte,Aureococcus anophagefferens

The trace element selenium (Se) is required for the biosynthesis of selenocysteine (Sec), the 21st amino acid in the genetic code, but its role in the ecology of harmful algal blooms (HABs) is unknown. Here, we examined the role of Se in the biology and ecology of the harmful pelagophyte, Aureococcus anophagefferens, through cell culture, genomic analyses, and ecosystem studies. This organism has the largest and the most diverse selenoproteome identified to date that consists of at least 59 selenoproteins, including known eukaryotic selenoproteins, selenoproteins previously only detected in bacteria, and novel selenoproteins. The A. anophagefferens selenoproteome was dominated by the thioredoxin fold proteins and oxidoreductase functions were assigned to the majority of detected selenoproteins. Insertion of Sec in these proteins was supported by a unique Sec insertion sequence. Se was required for the growth of A. anophagefferens as cultures grew maximally at nanomolar Se concentrations. In a coastal ecosystem, dissolved Se concentrations were elevated before and after A. anophagefferens blooms, but were reduced by >95% during the peak of blooms to 0.05 nℳ. Consistent with this pattern, enrichment of seawater with selenite before and after a bloom did not affect the growth of A. anophagefferens, but enrichment during the peak of the bloom significantly increased population growth rates. These findings demonstrate that Se inventories, which can be anthropogenically enriched, can support proliferation of HABs, such as A. anophagefferens through its synthesis of a large arsenal of Se-dependent oxidoreductases that fine-tune cellular redox homeostasis.     

Understanding selenoprotein function and regulation through the use of rodent models

Selenium (Se) is an essential micronutrient. Its biological functions are associated with selenoproteins, which contain this trace element in the form of the 21st amino acid, selenocysteine. Genetic defects in selenocysteine insertion into proteins are associated with severe health issues. The consequences of selenoprotein deficiency are more variable, with several selenoproteins being essential, and several showing no clear phenotypes. Much of these functional studies benefited from the use of rodent models and diets employing variable levels of Se. This review summarizes the data obtained with these models, focusing on mouse models with targeted expression of individual selenoproteins and removal of individual, subsets or all selenoproteins in a systemic or organ-specific manner. This article is part of a Special Issue entitled: Cell Biology of Metals.