scholarly journals Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1456 ◽  
Author(s):  
George Kontoghiorghes ◽  
Christina Kontoghiorghe
Keyword(s):  
Free Radical ◽  
Iron Metabolism ◽  
Metabolic Pathways ◽  
Physiological Activity ◽  
Genetic Disorders ◽  
Iron Complex ◽  
Idiopathic Hemochromatosis ◽  
Living Organisms ◽  
Almost All ◽  
And Function

Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology.

Pentose Phosphate Pathway in Disease and Therapy

2014 ◽  
Vol 995 ◽  
pp. 1-27 ◽  
Author(s):  
Mahbuba Rahman ◽  
M. Rubayet Hasan
Keyword(s):  
Metabolic Pathways ◽  
Cell Cycle Progression ◽  
Metabolic Diseases ◽  
Pentose Phosphate ◽  
Cycle Progression ◽  
Novel Drugs ◽  
Abnormal Cells ◽  
Living Organisms ◽  
And Function

Pentose phosphate (PP) pathway, which is ubiquitously present in all living organisms, is one of the major metabolic pathways associated with glucose metabolism. The most important functions of this pathway includes the generation of reducing equivalents in the form of NADPH for reductive biosynthesis, and production of ribose sugars for the biosynthesis of nucleotides, amino acids, and other macromolecules required by all living cells. Under normal conditions of growth, PP pathway is important for cell cycle progression, myelin formation, and the maintenance of the structure and function of brain, liver, cortex and other organs. Under diseased conditions, such as in cases of many metabolic, neurological or malignant diseases, pathological mechanisms augment due to defects in the PP pathway genes. Adoption of alternative metabolic pathways by cells that are metabolically abnormal, or malignant cells that are resistant to chemotherapeutic drugs often plays important roles in disease progression and severity. Accordingly, the PP pathway has been suggested to play critical roles in protecting cancer or abnormal cells by providing reduced environment, to protect cells from oxidative damage and generating structural components for nucleic acids biosynthesis. Novel drugs that targets one or more components of the PP pathway could potentially serve to overcome challenges associated with currently available therapeutic options for many metabolic and non-metabolic diseases. However, careful designing of drugs is critical that takes into the accounts of cell’s broader genomic, proteomic and metabolic contexts under consideration, in order to avoid undesirable side-effects. In this review, we discuss the role of PP pathway under normal and abnormal physiological conditions and the potential of the PP pathway as a target for new drug development to treat metabolic and non-metabolic diseases.

scholarly journals Metallothioneins: Diverse Protein Family to Bind Metallic Ions

2021 ◽  
Author(s):  
Ettiyagounder Parameswari ◽  
Tamilselvan Ilakiya ◽  
Veeraswamy Davamani ◽  
Periasami Kalaiselvi ◽  
Selvaraj Paul Sebastian
Keyword(s):  
Metal Ions ◽  
Growth Regulation ◽  
Class I ◽  
Reduced Form ◽  
Metallic Ions ◽  
Class Iii ◽  
Structure Conservation ◽  
Living Organisms ◽  
Almost All ◽  
And Function

Metallothionein’s (MTs) are the lower molecular weight (6-7 kDa) proteins that are found to be present in almost all organism types ranging from prokaryotes to eukaryotes species. MT are the metal detecting proteins that can mitigate the effect caused by the excess metal ions. They are also found to be involved in cellular process such as cell growth regulation, ROS (Reactive Oxygen Species) and DNA repair. The protein was termed as Metallothionein due to the unusual higher metal (metallo) and the sulfur (thiol) content. They are further grouped into 3 classes viz., class I, II and III. The Class I and II MTs are polypeptides that were obtained from direct gene products, the class III MTs are from the cysteine-rich non-translational molecules that are termed as phytochelatins. The metal ions are been sequestered through the MTs with Cys rich motifs. All the cysteines are present in the reduced form and are been co-ordinated through the mercaptide bonds. The cysteines present in the MTs are preserved across the species, it is supposed that, cysteines are essential for the function and the MTs are required for the life. Metallothionins structure, conservation in evolution, their ubiquitous nature of occurrence, the genes redundancy and the programmed MTs synthesis in development, regeneration and reproduction of living organisms are some of the weighty arguments in suspecting MTs to also serve others and perhaps the high particular metal-related cellular roles. In this chapter, there is a detailed discussion about Metallothionein its structure, occurrence and function.

scholarly journals The Current Knowledge of Invertebrate Aquaporin Water Channels with Particular Emphasis on Insect AQPs

2010 ◽  
Vol 2 (2) ◽  
pp. 91-104 ◽  
Author(s):  
Ewa Tomkowiak ◽  
Joanna Romana Pienkowska
Keyword(s):  
Current Knowledge ◽  
Water Channels ◽  
Survival Strategies ◽  
Feeding Strategies ◽  
Transmembrane Segments ◽  
Single Organism ◽  
Living Organisms ◽  
Almost All ◽  
And Function ◽  
Hostile Environments

SummaryAquaporins (AQPs) or water channels are some of the most ubiquitous integral membrane proteins, and are present in all living organisms. Their presence in the lipid bilayer of cell membranes considerably increases their permeability to water and, in some cases, to other small solutes. All AQPs, identified thus far, share the same structure, comprising of six transmembrane segments and two conserved regions forming the pore. Depending on the transported solutes, AQPs can be divided into two classes: ‘classical’ aquaporins (permeable only to water) and aquaglyceroporins (permeable also to glycerol and/or other solutes). Many subtypes of AQPs coexist in a single organism. Localization of particular subtypes of AQPs is tissue-specific. AQPs have been well characterized in almost all vertebrate classes. However, little is known about their counterparts in invertebrates. Most of the water channels characterized in invertebrates are found in insects. Therefore, the knowledge of aquaporins in invertebrates is generally limited to the information concerning water channels in this class of organism. Insects are characterized by an astonishing variety of physiological adaptations, notable in their feeding strategies or survival strategies in hostile environments. An example of such, is feeding on blood, or tolerating extreme cold or drought. It is likely that many of these adaptation patterns emerged due to the expression and regulation of particular aquaporins. Here we review the current state of knowledge of invertebrate AQPs (of insects and nematodes) and compare their structure and function with mammalian water channels

scholarly journals Molybdenum Cofactor Biology and Disorders Related to Its Deficiency; A Review Study

2019 ◽  
Author(s):  
Navid Ghasemzadeh ◽  
Elham Karimi-Nazari ◽  
Fatemeh Yaghoubi ◽  
Sadegh Zarei ◽  
Fatemeh Azadmanesh ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Genetic Disorders ◽  
Aldehyde Oxidase ◽  
Iron Complex ◽  
Molybdenum Cofactor ◽  
Biologically Active ◽  
Definitive Treatment ◽  
Gene Therapies ◽  
Bioactive Component ◽  
Normal Human

Background: Molybden, as a vital and essential micronutrient is directly involved in the metabolism of other elements including carbon, sulfur, and nitrogen. Molybdenum alone is not biologically active unless it binds to specific cofactors. Except for the bacterial nitrogenase, which contains molybdenum-Iron complex, molybdenum cofactor (Moco) is considered as the bioactive component placed in active site regions of molybdenum-containing enzymes. This review aimed to discuss the biological mechanisms involved in molybdenum metabolism highlighting Molybdenum cofactor deficiencies. Methods: Articles indexed in Pubmed, Google Scholar, and Scopus databases were used to extract the required information. Results: Moco, as the cofactor of sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase, and nitrite reductase plays a substantial role in maintaining normal body homeostasis and reactive oxygen species (ROS) production. Lack of Moco is found to be associated with many inborn genetic disorders, such as mental retardation, brain immaturity, nervous shocks, and neurodegenerative diseases. Conclusion: Moco insufficiency compromises normal human body metabolism since it is reported to regulate the metabolic pathways of other elements. Although in recent years, substitution- and gene-therapies have been introduced to restore the metabolic pathways of patients with MoCD type A and B, the definitive treatment for this type of inborn disease has still remained ill-defined. More investigations are needed to completely understand the underlying pathophysiology of molybdenum-related diseases.

scholarly journals Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes

2018 ◽  
Vol 11 (3) ◽  
pp. 84 ◽  
Author(s):  
Ana Gomes ◽  
Ana Moreira ◽  
Gonçalo Mesquita ◽  
Maria Gomes
Keyword(s):  
Iron Metabolism ◽  
Recent Literature ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Different Types ◽  
Essential Nutrient ◽  
Living Organisms ◽  
Almost All ◽  
And Control ◽  
Ongoing Infection

Iron is an essential nutrient for almost all living organisms, but is not easily made available. Hosts and pathogens engage in a fight for the metal during an infection, leading to major alterations in the host’s iron metabolism. Important pathological consequences can emerge from the mentioned interaction, including anemia. Several recent reports have highlighted the alterations in iron metabolism caused by different types of infection, and several possible therapeutic strategies emerge, based on the targeting of the host’s iron metabolism. Here, we review the most recent literature on iron metabolism alterations that are induced by infection, the consequent development of anemia, and the potential therapeutic approaches to modulate iron metabolism in order to correct iron-related pathologies and control the ongoing infection.

Structure and function of 5S rRNA in the ribosome

1995 ◽  
Vol 73 (11-12) ◽  
pp. 869-876 ◽  
Author(s):  
Alexey A. Bogdanov ◽  
Olga A. Dontsova ◽  
Svetlana S. Dokudovskaya ◽  
Inna N. Lavrik
Keyword(s):  
Ribosomal Proteins ◽  
5S Rrna ◽  
23S Rrna ◽  
Order Structure ◽  
Structural Domain ◽  
Experimental Approaches ◽  
Living Organisms ◽  
Almost All ◽  
And Function

5S rRNA is a small RNA molecule that is a component of a ribosome from almost all living organisms. In this review, we discuss the biogenesis of 5S rRNA and its properties as an independent structural domain of a ribosome as well as the current concepts concerning the higher order structure of 5S rRNA in free state and in its complexes with ribosomal proteins and its folding in the ribosome. Special attention is paid to recent experimental approaches that have been useful in 5S rRNA studies. Our own data on topography of 5S rRNA in the ribosomes are discussed in detail. The hypothesis describing the possible functional role of 5S rRNA for ribosome functioning is discussed.Key words: 5S rRNA, ribosomes, 23S rRNA, site-directed chemical cross-linking, RNA folding.

scholarly journals Modulation of Innate Immune Toxicity by Silver Nanoparticle Exposure and the Preventive Effects of Pterostilbene

2021 ◽  
Vol 22 (5) ◽  
pp. 2536
Author(s):  
Rong-Jane Chen ◽  
Chiao-Ching Huang ◽  
Rosita Pranata ◽  
Yu-Hsuan Lee ◽  
Yu-Ying Chen ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Good Alternative ◽  
Innate Immune ◽  
Toxic Effects ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Cytokines And Chemokines ◽  
Living Organisms ◽  
And Function ◽  
Immune Toxicity

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.

scholarly journals Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 350
Author(s):  
Julianty Frost ◽  
Mark Frost ◽  
Michael Batie ◽  
Hao Jiang ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Regulator ◽  
Hydroxylase Activity ◽  
Control Of Gene Expression ◽  
Prolyl Hydroxylases ◽  
Chromatin Organisation ◽  
Sense And Respond ◽  
Almost All ◽  
And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

scholarly journals Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3951
Author(s):  
Sarva Keihani ◽  
Verena Kluever ◽  
Eugenio F. Fornasiero
Keyword(s):  
Neuronal Differentiation ◽  
Neuronal Excitability ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Regulatory Mechanisms ◽  
Control Robustness ◽  
Living Organisms ◽  
And Function ◽  
Regulatory Functions ◽  
Neuronal Physiology

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

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