Endocytosis of G Protein-Coupled Receptors and Their Ligands: Is There a Role in Metal Trafficking?

The prevalence of metal dysregulation in many neurodegenerative and neurocognitive disorders has compelled many studying such diseases to investigate the mechanisms underlying metal regulation in the central nervous system. Metal homoeostasis is often complex, with sophisticated, multilayered pathways in operation. G protein-coupled receptors are omnipresent on cell membranes and have intriguing mechanisms of endocytosis and trafficking that may be useful in metal homoeostasis. Indeed, many receptors and/or their cognate ligands are able to bind metals, and in many cases metals are considered to have neuromodulatory roles as a result of receptor binding. In this mini-review, we outline the structural and functional aspects of G protein-coupled receptors with a focus on the mechanisms leading to endocytosis and cellular trafficking. We further highlight how this may help in the trafficking of metal ions, notably copper.     

Metal Ion availability in mitochondria

Transition metal ions are required for many aspects of mitochondrial physiology. Copper, iron, manganese and zinc are cofactors in metalloenzymes and metalloproteins within the organelle. Little is known how cells maintain optimal pools of these metal ions for mitochondrial function. This review documents the available literature on mitochondrial metal ion pools and protein metallation reactions. Upon perturbation in metal pools, mis-metallation reactions do occur. Thus, regulation of metal ion accessibility and bioavailability must exist.     

重金属污染生态学研究现状与展望

重金属污染生态学的研究迄今已有近 5 0 a的历史 ,在土壤重金属元素背景值和环境标准的制定、重金属在环境中的迁移转化、重金属污染治理、元素分析测定方法和规范、对生物体的毒性及生物体的响应等方面取得了很多研究成果 ,出版了很多专著。在对重金属污染生态学研究进行简要回顾的基础上 ,以重金属在生物体内的行为特征 (吸收、迁移、富集、毒害、解毒和抗性等 )为主线 ,从微观和宏观水平 ,系统综述了目前该领域的研究现状 ,分析了尚存在的一些问题 ,最后从生物对重金属污染适应的分子机理、治理方法和技术的创新性、复合污染下环境标准制定的科学化以及重金属污染条件下全球生物进化的趋势预测等方面作了研究展望     

Defining the catalytic metal ion interactions in the Tetrahymena ribozyme reaction

Divalent metal ions play a crucial role in catalysis by many RNA and protein enzymes that carry out phosphoryl transfer reactions, and defining their interactions with substrates is critical for understanding the mechanism of biological phosphoryl transfer. Although a vast amount of structural work has identified metal ions bound at the active site of many phosphoryl transfer enzymes, the number of functional metal ions and the full complement of their catalytic interactions remain to be defined for any RNA or protein enzyme. Previously, thiophilic metal ion rescue and quantitative functional analyses identified the interactions of three active site metal ions with the 3'- and 2'-substrate atoms of the Tetrahymena group I ribozyme. We have now extended these approaches to probe the metal ion interactions with the nonbridging pro-S(P) oxygen of the reactive phosphoryl group. The results of this study combined with previous mechanistic work provide evidence for a novel assembly of catalytic interactions involving three active site metal ions. One metal ion coordinates the 3'-departing oxygen of the oligonucleotide substrate and the pro-S(P) oxygen of the reactive phosphoryl group; another metal ion coordinates the attacking 3'-oxygen of the guanosine nucleophile; a third metal ion bridges the 2'-hydroxyl of guanosine and the pro-S(P) oxygen of the reactive phosphoryl group. These results for the first time define a complete set of catalytic metal ion/substrate interactions for an RNA or protein enzyme catalyzing phosphoryl transfer.     

Reactions of Low Valent Transition-Metal Complexes with Hydrogen Peroxide. Are they “Fenton-Like” or Not? 3. The Case of Fe(II){N(CH2CO2)3}(H2O)2

Usually the toxicity of superoxide is attributed lo its ability to reduce metal ions and subsequently reoxidation of the metal by hydrogen peroxide yields deleterious oxidizing species. As many other nontoxic biological reductants reduce metal compounds, we suggest that part of the mechanism of superoxide toxicity results from its ability to oxidize metal ions bound to biological targets, which subsequently degrade the target via an intramolecular electron Transfer reaction.     

What is Unique About Superoxide Toxicity as Compared to Other Biological Reductants? — A Hypothesis

Usually the toxicity of superoxide is attributed lo its ability to reduce metal ions and subsequently reoxidation of the metal by hydrogen peroxide yields deleterious oxidizing species. As many other nontoxic biological reductants reduce metal compounds, we suggest that part of the mechanism of superoxide toxicity results from its ability to oxidize metal ions bound to biological targets, which subsequently degrade the target via an intramolecular electron Transfer reaction.     

Chloroplastic and mitochondrial metal homeostasis

Transition metal deficiency has a strong impact on the growth and survival of an organism. Indeed, transition metals, such as iron, copper, manganese and zinc, constitute essential cofactors for many key cellular functions. Both photosynthesis and respiration rely on metal cofactor-mediated electron transport chains. Chloroplasts and mitochondria are, therefore, organelles with high metal ion demand and represent essential components of the metal homeostasis network in photosynthetic cells. In this review, we describe the metal requirements of chloroplasts and mitochondria, the acclimation of their functions to metal deficiency and recent advances in our understanding of their contributions to cellular metal homeostasis, the control of the cellular redox status and the synthesis of metal cofactors.     

Zinc transporters and the cellular trafficking of zinc

Zinc is an essential nutrient for all organisms because this metal serves as a catalytic or structural cofactor for many different proteins. Zinc-dependent proteins are found in the cytoplasm and within many organelles of the eukaryotic cell including the nucleus, the endoplasmic reticulum, Golgi, secretory vesicles, and mitochondria. Thus, cells require zinc transport mechanisms to allow cells to efficiently accumulate the metal ion and distribute it within the cell. Our current knowledge of these transport systems in eukaryotes is the focus of this review.     

利用黑腹果蝇（Drosophila melanogaster）研究微量金属元素代谢

微量金属参与了生物体许多化学反应过程,同时也可作为蛋白质的辅基或辅因子起作用,对机体生长发育以及正常生物功能的维持具有重要作用;微量金属元素的代谢失衡与生物体许多疾病密切相关,如威尔森氏病、门克斯病、铁色素沉积、肠变性皮炎以及一些神经退行性疾病。黑腹果蝇（Drosophila melanogaster）是遗传背景清楚、生活周期短、操作方便的模式生物,利用果蝇研究金属离子代谢以及金属离子代谢与疾病的联系具有独特的优势,近年来,随着果蝇基因组测序的完成以及许多转基因果蝇株的建立,果蝇也越来越多的用于金属离子代谢的研究。介绍了近年来果蝇在金属离子代谢研究领域的进展,以及其与神经退行性疾病关系研究上的一些应用。     

Metal accumulation and tolerance in wetland plants

This paper briefly reviews the progress in studies of wetland plants in terms of heavy metal pollution. The current research mainly includes the following areas: (1) metal uptake, translocation, and distributions in wetland plants and toxicological effects on wetland plants, (2) radial oxygen loss (ROL) of wetland plants and its effects on metal mobility in rhizosphere soils, (3) constitutional metal tolerance in wetland plants, and (4) mechanisms of metal tolerance by wetland plants. Although a number of accomplishments have been achieved, many issues still remain unanswered. The future research effort is likely to focus on the ROL of wetland plants affecting metal speciation and bioavailability in rhizosphere soils, and the development of rhizosphere management technologies to facilitate and improve practical applications of phytoremediation of metalpolluted soils.     

Metal accumulation and tolerance in wetland plants

This paper briefly reviews the progress in studies of wetland plants in terms of heavy metal pollution. The current research mainly includes the following areas: (1) metal uptake, translocation, and distributions in wetland plants and toxicological effects on wetland plants, (2) radial oxygen loss (ROL) of wetland plants and its effects on metal mobility in rhizosphere soils, (3) constitutional metal tolerance in wetland plants, and (4) mechanisms of metal tolerance by wetland plants. Although a number of accomplishments have been achieved, many issues still remain unanswered. The future research effort is likely to focus on the ROL of wetland plants affecting metal speciation and bioavailability in rhizosphere soils, and the development of rhizosphere management technologies to facilitate and improve practical applications of phytoremediation of metal-polluted soils.     

Modification of radiation response by metal complexes: a review with emphasis of nonplatinum studies

There is a need to develop compounds which alter the effects of radiation, particularly in the hypoxic radioresistant cell, following the limited success to date of the electron-affinic nitroimidazoles. The chemistry of transition metals is briefly outlined to point out certain aspects which might be exploited in the design of radiosensitizers. The best known clinical example of a metal complex which enhances the effect of radiation in hypoxic cells is the successful antineoplastic cisplatin. Past studies on enhancement of radiation damage by complexes of metals other than platinum, mainly in bacterial spores and bacterial and mammalian cells, have been summarized according to the metal used. The many mechanisms by which metal complexes could interact with radiation are outlined, and examples are given where possible. This survey emphasizes the need for a systematic study of the effect of metal/ligand variation on radiosensitization with regard to mechanisms of action to assess the potential of these compounds as radiosensitizers. Metal complexes offer many advantages, both for the study of mechanisms by which radiation kills cells and for drug development.     

NMR structures of paramagnetic metalloproteins

Metalloproteins represent a large share of the proteome and many of them contain paramagnetic metal ions. The knowledge, at atomic resolution, of their structure in solution is important to understand processes in which they are involved, such as electron transfer mechanisms, enzymatic reactions, metal homeostasis and metal trafficking, as well as interactions with their partners. Formerly considered as unfeasible, the first structure in solution by nuclear magnetic resonance (NMR) of a paramagnetic protein was obtained in 1994. Methodological and instrumental advancements pursued over the last decade are such that NMR structure of paramagnetic proteins may be now routinely obtained. We focus here on approaches and problems related to the structure determination of paramagnetic proteins in solution through NMR spectroscopy. After a survey of the background theory, we show how the effects produced by the presence of a paramagnetic metal ion on the NMR parameters, which are in many cases deleterious for the detection of NMR spectra, can be overcome and turned into an additional source of structural restraints. We also briefly address features and perspectives given by the use of 13C-detected protonless NMR spectroscopy for proteins in solution. The structural information obtained through the exploitation of a paramagnetic center are discussed for some Cu2+ -binding proteins and for Ca2+ -binding proteins, where the replacement of a diamagnetic metal ion with suitable paramagnetic metal ions suggests novel approaches to the structural characterization of proteins containing diamagnetic and NMR-silent metal ions.     

Metal ion ligands in hyperaccumulating plants

Metal-hyperaccumulating plants have the ability to take up extraordinary quantities of certain metal ions without succumbing to toxic effects. Most hyperaccumulators select for particular metals but the mechanisms of selection are not understood at the molecular level. While there are many metal-binding biomolecules, this review focuses only on ligands that have been reported to play a role in sequestering, transporting or storing the accumulated metal. These include citrate, histidine and the phytosiderophores. The metal detoxification role of metallothioneins and phytochelatins in plants is also discussed.     

Metalloregulation of Gram-positive pathogen physiology

Owing to the unique redox potential of transition metals, many of these elements serve important roles as cofactors in numerous enzymes. However, the reactive nature of metal becomes an intracellular threat when these ions are present in excess. Therefore, all organisms require mechanisms for sensing small fluctuations in metal levels to maintain a controlled balance of uptake, efflux, and sequestration. The ability to sense metal ion concentration is especially important for the survival of pathogenic bacteria because host organisms can both restrict access to essential metals from invading pathogens and utilize the innate toxicity of certain metals for bacterial killing. Host-induced metal ion fluctuations must be rapidly sensed by pathogenic bacteria so that they can activate metal transport systems, alter their physiology to accommodate differences in metal concentrations, and regulate the expression of virulence factors.     

重金属胁迫下土壤微生物和微生物过程研究进展

通过对重金属胁迫下土壤微生物和微生物过程研究的进程和研究进展的归纳综述,分析了该研究尚存在的问题,并阐述了其可能原因．认为土壤微生物和微生物学过程的重金属胁迫研究存在如下问题：一是从实验室、田间试验和实地监测得到的结果间无法进行比较,从而使实验室和田间试验的研究丧失了其科学指导意义,并且在实地监测研究中缺乏相应的“精确”对照;二是在重金属的胁迫下土壤微生物不但数量有消长,而且区系结构上也发生了变化,但是用于校园微生物区系结构变化的手段(PLFA、BI-OLOG和DNA等方法)尚处在探索阶段并需要昂贵的设备,难以普及,需发展一些可广泛普及的新方法来代替传统的平板分离法分析土壤微生物结构;三是重金属对土壤微生物和微生物过程产生胁迫的形态、离子效应和根际效应尚未得到有效的研究和探讨;四是土壤微生物和微生物过程重金属胁迫的表征体系尚未建立．     

儿茶素与金属离子相互作用及其生物学意义

儿茶素的医学保健功效已经得到广泛证实,其与金属离子的相互作用也随之成为无机生物化学和医学等交叉研究领域的热点。综述了儿茶素与金属离子的相互作用及其生物学意义,并对其研究前景进行了展望。     

壳聚糖金属离子配合物吸附尿素性能研究

由于尿素吸附剂存在吸附容量低、吸附选择性差、生物相容性和血液相容性差等缺点,使人工肾和口服尿素吸附剂的应用受到限制．近几年,尿素吸附材料方面的研究进展较快,主要有：１９９０年,藤田良枝用活性炭作尿素吸附剂,吸附量为９０ｍｇ／ｇ（尿素初始浓度为２１００ｍｇ／Ｌ）,吸附容量低,且微炭粒易脱落,有造成栓塞的危险,不宜作人工肾材料［１］;１９９３年,何炳林等用交联聚丙烯酸固载化氧化β环糊精作尿素吸附材料,吸附容量较高,为８２１ｍｇ／ｇ（尿素的初始浓度为１３００ｍｇ／Ｌ）．由于其利用的是Ｓｃｈｉｆｆ…     

Metal-binding proteins and peptides in bioremediation and phytoremediation of heavy metals

The expression of metal-binding proteins or peptides in microorganisms and plants in order to enhance heavy metal accumulation and/or tolerance has great potential. Several different peptides and proteins have been explored. This review focuses on cadmium (Cd) because of the significant importance of this metal and because of its global presence in many food materials.     

The role of transition metal homeostasis in plant seed development

For human health, transition metal accumulation in edible seeds like cereal grains is of worldwide importance, since Fe and Zn deficiencies are among the most prevalent human nutritional disorders in the world. There have been many recent developments in our understanding of the patterns in which transition metals accumulate in the seeds, the identity of some specific transporters that are required for efficient seed metal accumulation, and the central role played by the ubiquitous plant metal chelator nicotianamine (NA). These and other recent discoveries will be reviewed here.