Role Of Magnesium Ions Research Articles

Role of magnesium ions in modifying oxide growth rate on Zircaloy under breakaway corrosion regimes

General corrosion of nuclear reactor in core material like Zircaloy-2 and breakaway corrosion in particular are of great importance in ensuring its smooth long term operation. Metal ions like Mg2+ added to the coolant, to mitigate corrosion of other structural materials like Carbon steel, can get incorporated in the corrosion product oxide on Zircaloy-2 and alter its corrosion behavior. Plasma Electrolytic Oxidation (PEO) method was employed to investigate the effect of Mg2+ ions during breakaway corrosion of Zircaloy-2. The main objective was to understand the morphology, protectiveness, semiconducting properties of the Mg modified oxide films on Zircaloy-2 surface. DC potentials 300, 400 and 500 V were used to accelerate corrosion kinetics and form oxide mimicking the breakaway corrosion regime. Borate buffer (pH 9.8) was used as the electrolyte, and Mg acetate was added as Mg source for probing the effect of Mg2+ ions. Oxide morphology depended largely on the formation potentials. The presence of magnesium resulted in thinner oxides with lower defect densities. GIXRD of the oxide showed stabilization of tetragonal phase in presence of Mg at 300 and 400 V. Oxide resistance and charge transfer resistances measured by EIS were observed to be higher due to Mg incorporation at these potentials. Mg addition facilitated formation of t-ZrO2. The electrochemical measurements suggested that the presence of Mg in ZrO2 could reduce the connected porosity in the oxide thereby stifling the diffusion paths. These factors lead to improved corrosion protectiveness of the oxide formed in the presence of Mg.

Resorbable Mg2+-Containing Phosphates for Bone Tissue Repair.

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play substantial roles in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. In this paper we provide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. We consider the role of magnesium ions in angiogenesis, which is an important process associated with osteogenesis. Finally, we summarize the biological properties of calcium magnesium phosphates for regeneration of bone.

On the Role of Magnesium Ions in the DNA-Scissoring Activity of the Restriction Endonuclease ApaI: Stochastic Kinetics from a Single Molecule to Mesoscopic Paradigm.

Biochemical reactions occurring inside cells have significant stochastic signatures due to the low copy number of reacting species. Kinetics of DNA cleavage by restriction endonucleases are no exception as established by single-molecule experiments. Here, we propose a simple reaction scheme to understand the role of the cofactor magnesium ion in the action of the endonuclease ApaI. The methodology is based on the waiting time distribution of cleavage product formation that enables us to determine the corresponding rate both analytically and numerically. The theory is developed at the single-molecule level and then generalized to the biologically relevant case of a population of DNA-endonuclease complexes present inside a cell. The theoretical rate versus cofactor concentration curve is matched with relevant single-molecule experimental data that reveals positive cooperativity of cofactor binding and provides a reliable estimate of model parameters. Furthermore, a parameter range is identified where the dispersion of the waiting time, measured using the coefficient of variation, is significantly lower than the Poisson limit and becomes minimum at the in vivo magnesium ion concentration level. Such low dispersion can play a role in the robust DNA-scissoring activity of ApaI under in vivo conditions.

Biochemical activity of magnesium ions on human osteoblast migration

Magnesium is well known as a biodegradable biomaterial that has been reported to promote bone remodeling in several studies; however, the underlying biological mechanism remains unclear. In the present study, the role of magnesium ions in the migration of U-2 OS cells, which are osteoblast-like cell lines, was investigated. Magnesium treatment did not significantly alter the global transcriptome of U-2 OS cells, but increased the protein expression level of SNAI2, an epithelial–mesenchymal transition (EMT) marker. In addition, it was confirmed that the junctional site localization of Zona-occludens 1 (ZO-1), a representative tight junction protein, was destroyed by magnesium treatment; furthermore, it was determined that cytoplasmic localization increased, and alkaline phosphatase (ALP) activity increased. The obtained results on the mechanism by which magnesium is involved in osteoblast migration, which is important for fracture healing, will contribute to the understanding of the bone-formation process in patients with osteoporosis and musculoskeletal injury.

Insights into the Role of Magnesium Ions in Affecting Osteogenic Differentiation of Mesenchymal Stem Cells.

Bone marrow mesenchymal stem cells (MSCs) are multipotent stem cells with the ability to differentiate into bone-producing cells, which is essential for bone formation. Magnesium biomedical materials, such as biodegradable matters with osteoinductive properties, play a vital role in the osteogenic differentiation of MSCs. International and Chinese studies have shown that magnesium ions, which are produced by biodegradation, mainly achieve this effect by regulating the expression of genes and proteins associated with osteogenesis, activating multiple signal pathways, elevating autophagic activities, and adjusting the pH in the microenvironment. It is of great significance to study the regulatory mechanisms and identify the optimal conditions that how magnesium ions promote osteogenic differentiation of MSCs. In this study, we summarized the regulatory mechanisms noted above.

The role of magnesium ions in bone regeneration involves the canonical Wnt signaling pathway

Magnesium (Mg)-based implants have become of interest to both academia and the medical industry. The attraction largely is due to Mg’s biodegradability and ability to enhance bone healing and formation. However, the underlying mechanism of how Mg regulates osteogenesis is still unclear. Based on our previous in vivo and molecular signaling work demonstrating the osteogenic effect of Mg, the current study aims to extend this work at the molecular level especially that we also observed and quantified mineral deposits in the bone marrow space in a rabbit ulna fracture model with Mg plates and screws. Histological analysis and quantitative results of micro-CT showed mineralized deposition and a significant increase in bone volume at 8 weeks and 16 weeks post-operative. These in vivo results led us to focus on studying the effect of Mg2+ on human bone marrow stromal cells (hBMSCs). The data presented in this manuscript demonstrate the activation of the canonical Wnt signaling pathway in hBMSCs when treated with 10 mM Mg2+. With additional Mg2+ present, the protein expression of active β-catenin was significantly increased to a level similar to that of the positive control. Immunocytochemistry and the increased expression of LEF1 and Dkk1, downstream target genes that are controlled directly by active β-catenin, demonstrated the protein translocation and the activation of transcription. Taken together, these data suggest that Mg2+ induces an osteogenic effect in the bone marrow space by activating the canonical Wnt signaling pathway, which in turn causes BMSCs to differentiate toward the osteoblast lineage. Statement of SignificanceMagnesium (Mg)-based alloys are being studied to be used in the field of implantable medical devices due to its natural biodegradability and the potential ability to promote bone regeneration. Despite many in vivo studies that demonstrated an increased new bone growth by implanting Mg-based devices, the underlying mechanism of this effect is still unclear. In order to safely use Mg-based implants on human and better control the osteogenic effect, it is necessary to understand the corresponding cellular response in the targeted area. The present study provides the rationale to study Mg ions on bone marrow stromal cells and shows the activation of canonical Wnt signaling pathway that promotes osteogenesis by in vivo and in vitro approaches.

Ketamine and magnesium common pathway of antidepressant action.

Depression is one of the major causes of disability worldwide. A proportion of adults with major depression fail to achieve remission with first-line treatment. Magnesium influences the neurotransmission involved in emotional processes, such as the serotonergic, noradrenergic, dopaminergic, GABAergic and glutamatergic systems. It has been reported that the mechanism of antidepressants' action is involved in the glutamatergic system. Theories about the role of magnesium ions in pathophysiology of major depressive disorder include blocking the glutamatergic N-methyl-D-aspartate receptor (NMDAR). Ketamine, NMDAR antagonist, was found to promote fast-acting antidepressant and antisuicidal effects. Magnesium and ketamine seem to be involved in key mechanisms of the major depression pathophysiology. The evidence in the paper discussed may indicate the synergistic interaction between magnesium and ketamine pharmacodynamic activity being of particular importance in mood disorders.

Roles of magnesium ions in vascular relaxation via calcium channel and cyclooxygenase pathway in isolated rat aorta

The impact of magnesium (Mg) on vascular tone is mainly due to its calcium antagonist activity resulting in smooth muscle relaxation. The present study was designed to determine the roles of nitric oxide and calcium ions in magnesium -induced vasorelaxation in rats aortic rings. In this study, the aorta contracted with NE (3x10-6M), pre-incubated with cyclooxygenase (COX) and epoxygenase inhibitors, then dose response curve(DRC) made to magnesium sulfate (MgSO4 ) served as a control. On the other hand, the aorta incubated with L-NAME (10 mM) ,nifedipine (10-5M) , indomethacin (10-5M) and clotrimazole (30 mM) for 20 minutes then contracted by nor-epinephrine (NE) and relaxed by MgSO4 doses. Interestingly, L-NAME shifted the DRC of MgSO4 to the left and elevated Emax significantly. Furthermore, p IC50 tended to increase in L-NAME pre-incubated aortic rings. Also, aortic rings that are pre-contracted with 10-6M NE in the absence of calcium ions shifted the DRC to the left but it significantly reduced pIC50. Furthermore, calcium channel blocker (Nifedipine) significantly reduced the relaxatory effects of magnesium ions and it markedly decreased Emax with altering pIC50 values significantly. The present results revealed that indomethacin pre-incubation slightly shifted the curve of MgSO4 to the right, while p IC50 was significantly increased and Emax did not significantly change in clotrimazole pre-incubation. In conclusions, the results of this study suggested that magnesium ions can probably relax aortic smooth muscles , and this is may be returned to in part to nitric oxide ,COX and epoxygenase enzyme pathways.

Magnesium in Intensive Care Unit : A Review

Aim of the work: there is an increased interest in the role of magnesium ions in clinical medicine, nutrition and physiology. Magnesium affects many cellular functions, including transport of potassium and calcium ions and modulates signal transduction, energy metabolism and cell proliferation. Magnesium deficiency is not uncommon among the general population: its intake has decreased over the years. Magnesium derangement results in various symptoms and signs; magnesium supplementation or intravenous infusion may be beneficial in various diseased states; so this review aimed to highlight the physiology of magnesium in humans, the derangement of magnesium in the form of hyper and hypomagnesemia , their clinical picture and the clinical and therapeutic uses of magnesium in the critical ill patients . Methods: references were obtained from Medline, Google Scholar and Ovid from 1960 to 2017. All categories of articles (clinical trials, reviews, or metaanalyses) on this topic were selected. Conclusion: magnesium is a critical physiological ion; it has many known indications in anesthesiology and intensive care because of its interactions with drugs used in intensive care. Intensive care specialists need to have a clear understanding of the role of this important cation. Magnesium is gaining recognition as a clinically important electrolyte in intensive care and emergency medicine .Recent clinical trials and case reports increase interest of magnesium as an effective therapeutic agent for potentially life-threatening problems such as torsade de pointes, digitalis toxicity, bronchospasm and alcohol withdrawal, subarachnoid hemorrhage, acute myocardial infarction, preecalmsia , eclamsia ,hypertension , diabetes , metabolic syndrome and cardiac arrhthymias .

An Open and Shut Case: The Interaction of Magnesium with MST Enzymes.

The shikimate pathway of bacteria, fungi, and plants generates chorismate, which is drawn into biosynthetic pathways that form aromatic amino acids and other important metabolites, including folates, menaquinone, and siderophores. Many of the pathways initiated at this branch point transform chorismate using an MST enzyme. The MST enzymes (menaquinone, siderophore, and tryptophan biosynthetic enzymes) are structurally homologous and magnesium-dependent, and all perform similar chemical permutations to chorismate by nucleophilic addition (hydroxyl or amine) at the 2-position of the ring, inducing displacement of the 4-hydroxyl. The isomerase enzymes release isochorismate or aminodeoxychorismate as the product, while the synthase enzymes also have lyase activity that displaces pyruvate to form either salicylate or anthranilate. This has led to the hypothesis that the isomerase and lyase activities performed by the MST enzymes are functionally conserved. Here we have developed tailored pre-steady-state approaches to establish the kinetic mechanisms of the isochorismate and salicylate synthase enzymes of siderophore biosynthesis. Our data are centered on the role of magnesium ions, which inhibit the isochorismate synthase enzymes but not the salicylate synthase enzymes. Prior structural data have suggested that binding of the metal ion occludes access or egress of substrates. Our kinetic data indicate that for the production of isochorismate, a high magnesium ion concentration suppresses the rate of release of product, accounting for the observed inhibition and establishing the basis of the ordered-addition kinetic mechanism. Moreover, we show that isochorismate is channeled through the synthase reaction as an intermediate that is retained in the active site by the magnesium ion. Indeed, the lyase-active enzyme has 3 orders of magnitude higher affinity for the isochorismate complex relative to the chorismate complex. Apparent negative-feedback inhibition by ferrous ions is documented at nanomolar concentrations, which is a potentially physiologically relevant mode of regulation for siderophore biosynthesis in vivo.

Role of magnesium ions in the reaction mechanism at the interface between Tm1631 protein and its DNA ligand.

A protein, Tm1631 from the hyperthermophilic organism Thermotoga maritima belongs to a domain of unknown function protein family. It was predicted that Tm1631 binds with the DNA and that the Tm1631–DNA complex is an endonuclease repair system with a DNA repair function (Konc et al. PLoS Comput Biol 9(11): e1003341, 2013). We observed that the severely bent, strained DNA binds to the protein for the entire 90 ns of classical molecular dynamics (MD) performed; we could observe no significant changes in the most distorted region of the DNA, where the cleavage of phosphodiester bond occurs. In this article, we modeled the reaction mechanism at the interface between Tm1631 and its proposed ligand, the DNA molecule, focusing on cleavage of the phosphodiester bond. After addition of two Mg2+ ions to the reaction center and extension of classical MD by 50 ns (totaling 140 ns), the DNA ligand stayed bolted to the protein. Results from density functional theory quantum mechanics/molecular mechanics (QM/MM) calculations suggest that the reaction is analogous to known endonuclease mechanisms: an enzyme reaction mechanism with two Mg2+ ions in the reaction center and a pentacovalent intermediate. The minimum energy pathway profile shows that the phosphodiester bond cleavage step of the reaction is kinetically controlled and not thermodynamically because of a lack of any energy barrier above the accuracy of the energy profile calculation. The role of ions is shown by comparing the results with the reaction mechanisms in the absence of the Mg2+ ions where there is a significantly higher reaction barrier than in the presence of the Mg2+ ions.Graphical abstractA protein, Tm1631 from the hyperthermophilic organism Thermotoga maritima belongs to a domain of unknown function protein family. We modeled the reaction mechanism at the interface between Tm1631 and its proposed ligand, the DNA molecule, focusing on cleavage of the phosphodiester bondElectronic supplementary materialThe online version of this article (doi:10.1186/s13065-016-0188-6) contains supplementary material, which is available to authorized users.

The Earliest Discovery of the Role of Magnesium Ions on Stabilizing the Tertiary Structure of the Transfer RNA and Its Biological Significance <br>—A Short Memoir

In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.

The pathomechanisms underlying tinnitus in the cochlea and the role of magnesium ions

The pathomechanisms underlying tinnitus in the cochlea and the role of magnesium ions

On using magnesium and potassium ions in RNA experiments.

RNA is a dynamic molecule that can adopt different conformations under different conditions. In the cell, the negatively charged RNA is expected to interact with potassium and magnesium ions. The role of magnesium ions has been extensively studied in RNA, as it is necessary for proper folding of RNA and acts as a nucleophile in many reactions catalyzed by RNA. A short overview of the role of magnesium and potassium in RNA structures is provided here in order to demonstrate the need for carefully choosing the experimental conditions for RNA studies.

Role of magnesium ions on osteogenic response in bone marrow stromal cells

Biodegradable magnesium (Mg) alloys have been investigated for craniofacial and orthopedic bone fracture fixation due to their initial mechanical strength and high biocompatibility. Although Mg alloys have been reported to enhance bone regeneration in vivo, and enhanced osteogenic marker expression in human bone marrow stromal cells (hBMSCs) cultured in Mg alloy extract was reported, however, the biological mechanism is not fully understood. Thus, it is important to elucidate which signaling pathway in the hBMSCs are activated by Mg2+ that enhances bone formation. We investigated possible mechanisms underlying effects of Mg2+ on bone regeneration by culturing differentiated and undifferentiated hBMSCs in the presence of culture medium containing 10 mM MgSO4 both with or without osteogenic factors. mRNA expression of osteogenic genes was analyzed using quantitative PCR arrays. Quantitative PCR array data indicated increased mRNA expression of collagen type X and insulin-like growth factor 2, and decreased expression of integrin alpha 3 in the presence of 10 mM MgSO4. Moreover, Western blotting analysis showed enhanced expression of collagen type X, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-2α, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the presence of 10 mM MgSO4. In conclusion, 10 mM of MgSO4 enhanced the production of collagen type X and VEGF by hBMSCs. These results also suggest that Mg2+ released from bone fixation devices may promote bone regeneration by enhancing the production of collagen type X and VEGF of osteogenic cells in bone tissue.

Structure-based drug design of catechol-O-methyltransferase inhibitors for CNS disorders.

Catechol-O-methyltransferase (COMT) is of great importance in pharmacology because it catalyzes the metabolism (methylation) of endogenous and xenobiotic catechols. Moreover, inhibition of COMT is the drug target in the management of central nervous system (CNS) disorders such as Parkinson's disease due to its role in regulation of the dopamine level in the brain. The X-ray crystal structures for COMT have been available since 1994. The active sites for cofactor and substrate/inhibitor binding are well resolved to an atomic level, providing valuable insights into the catalytic mechanisms as well as the role of magnesium ions in catalysis. Determination of how the substrates/inhibitors bind to the protein leads to a structure-based approach that has resulted in potent and selective inhibitors. This review focuses on the design of two types of inhibitors (nitrocatechol-type and bisubstrate inhibitors) for COMT using the protein structures.

Role of Magnesium Ions and Ligand Stacking in the Adenine Riboswitch Folding

Riboswitches are RNA structured elements that modulate fundamental pathways in bacteria and plants. Depending on the availability of their sensed metabolite they undergo a conformational change that turns on or off gene expression. In the add adenine riboswitch from Vibrio Vulnificus there are three crucial spots for the switch between the two conformations: the P1 stem, the kissing-loops and the binding site for adenine. Our work is based on advanced in silico techniques, including atomistic molecular simulations, steered molecular dynamics, umbrella sampling, metadynamics and Hamiltonian replica exchange. First we investigated the P1-ligand dependent stabilization quantifying this effect in terms of free energy (Di Palma et al doi:10.1261/rna.040493.113). Then we evaluated the different contributions that Mg2+ and adenine give to the formation of the tertiary interactions between the two loops and we analysed the influence of these interactions on the binding site. The obtained data are in quantitative agreement with experiments. The atomistic description of metabolite binding, RNA-Mg2+ interaction, and tertiary-contact formation clarifies the details of the ligand-aptamer interactions and of the role of divalent cations in the global aptamer folding.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Role of magnesium ions on Improvement of Fermentative activity of local yeast isolates Saccharomyces cerevisiae for ethanol production

The interest in bio-ethanol increase as biofuel, it seems to be a good alternative for fossil fuels. The growth of yeast Saccharomyces cerevisiae is influence in micronutrient like ions. This research aims to evaluate the influence different amount of magnesium as co-enzyme in growth and fermentation of yeast S. cerevisiae which isolated from different local sources. The batch fermentation process was followed at different magnesium concentrations as magnesium chloride at incubation temperature 30C○ and pH 4.5, best supplement concentration was 1.25 gm/l by measuring the mass of the released carbon dioxide. Supplement media with magnesium prolonged exponential growth, reduced the decline in fermentation activity resulting in reduced the time required for the conversion glucose into ethanol.

Kinetic and Structural Features of a Dyestuff Coaggregation Studied by Time-Resolved Static Light Scattering

A binary dyestuff aggregate with a distinct stoichiometry is formed in dilute aqueous solution upon addition of Mg(2+) ions. The aggregation process was investigated with time-resolved multiangle static light scattering resulting in a sequence of static scattering curves. The scattering curves were analyzed with respect to the aggregation kinetics as well as the structure of the growing aggregates. The aggregation kinetics was based on the time evolution of the weight-averaged molar mass values extracted from the intercepts of the static scattering curves. A kinetic model that considers solely a nucleation step and monomer addition in its most simple form was developed in order to describe the evolution of time-dependent mass data. In addition, a kinetic model introduced by Lomakin et al. (Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 1125) for the description of β-amyloid aggregation was adapted to the same experimental data. Application of the two kinetic models offered significant information on the role of magnesium ions within the aggregation process and provided a deeper understanding of the aggregation mechanism. Correlation of the size parameters extracted from the initial slopes of the scattering curves with the respective mass data as well as direct fitting of the scattering curves with the wormlike chain model yield a consistent set of model parameters.

English

  The advent of highly efficient, environmentally friendly and cost effective fermentation technology has given impetus to research in the field of optimizing nutritional parameters for optimum yeast fermentative performance. Very high gravity fermentation is a novel fermentation technology that provides an increased production capacity from same size fermentation facilities, with outstanding benefits that includes: high ethanol yield per fermentable mash, considerable savings in energy and process water usage, and effluents with low biological oxygen demand amongst others. Limitations to full commercialization of the technology have been attributed to deleterious effects of the fermentation condition on yeast physiology which include high osmotic stress and ethanol toxicity amongst others. The impact of these physiological stresses on yeast cells during high substrate fermentation manifest as sluggish and incomplete fermentation with high residual sugars in beer, reduced ethanol yield, disproportionate synthesis of esters and generation of respiratory deficient yeast crop. However, compelling evidence has implicated magnesium ions with numerous biological processes and more importantly, with the role of curtailing the impact of these stress conditions. Hence, this review highlights two potential stress conditions of very high gravity fermentation; their mechanism of inhibition versus yeast stress response mechanism, role of magnesium ions in yeast physiology and its impact on fermentation processes. The knowledge emphasized herein will be of practical importance to industrial fermentation processes, as it provides feasible clues to improving yeast fermentative performance under high substrate conditions - with perspectives to precise magnesium regulation in yeast.   Key words: Very high gravity fermentation, osmotic stress, ethanol stress, yeast stress tolerance, magnesium ion.