scholarly journals Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1969
Author(s):  
Sonia Levi ◽  
Maddalena Ripamonti ◽  
Marko Dardi ◽  
Anna Cozzi ◽  
Paolo Santambrogio
Keyword(s):  
Physiological Condition ◽  
Physiological Role ◽  
Biochemical Properties ◽  
Cross Reactivity ◽  
Pathological Conditions ◽  
Human Ferritin ◽  
Ferritin Gene ◽  
New Type ◽  
Very High

In 2001, a new type of human ferritin was identified by searching for homologous sequences to H-ferritin in the human genome. After the demonstration that this ferritin is located specifically in the mitochondrion, it was called mitochondrial ferritin. Studies on the properties of this new type of ferritin have been limited by its very high homology with the cytosolic H-ferritin, which is expressed at higher levels in cells. This great similarity made it difficult to obtain specific antibodies against the mitochondrial ferritin devoid of cross-reactivity with cytosolic ferritin. Thus, the knowledge of the physiological role of mitochondrial ferritin is still incomplete despite 20 years of research. In this review, we summarize the literature on mitochondrial ferritin expression regulation and its physical and biochemical properties, with particular attention paid to the differences with cytosolic ferritin and its role in physiological condition. Until now, there has been no evidence that the alteration of the mitochondrial ferritin gene is causative of any disorder; however, the identified association of the mitochondrial ferritin with some disorders is discussed.

MYOSTATIN - A MODERN UNDERSTANDING OF THE PHYSIOLOGICAL ROLE AND SIGNIFICANCE IN THE DEVELOPMENT OF AGE-ASSOCIATED DISEASES

2021 ◽  
pp. 701-706
Author(s):  
А.А. Газданова ◽  
В.Г. Кукес ◽  
О.К. Парфенова ◽  
Н.Г. Сидоров ◽  
А.В. Перков ◽  
...  
Keyword(s):  
Muscle Growth ◽  
Physiological Role ◽  
Review Article ◽  
Negative Regulator ◽  
Transforming Growth Factors ◽  
Endogenous Factors ◽  
Pathological Conditions ◽  
Physiological Properties ◽  
The Family

Миостатин - белок, принадлежащий к классу миокинов, семейству трансформирующих факторов роста β (TGF-β). В обзорной статье, анализирующей данные литературы, показана ключевая роль миостатина в развитии старческой саркопении и кахексии при различных патологических состояниях, таких как рак, ХСН, ХБП, ХОБЛ и др. В статье рассматривается структура миостатина, подробная схема синтеза и его активации, механизм действия как негативного регулятора роста и дифференцировки мышц при этих патологических состояниях. Выделены основные физиологические свойства и клиническое значение. Рассмотрены экзогенные и эндогенные факторы, регулирующие экспрессию миостатина, и возможные механизмы их действия. Myostatin is a protein belonging to the myokine class, the family of transforming growth factors β (TGF-β). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions. The main physiological properties and clinical significance are highlighted. Exogenous and endogenous factors regulating myostatin expression and possible mechanisms of their action are considered.

scholarly journals Update in TSH Receptor Agonists and Antagonists

2012 ◽  
Vol 97 (12) ◽  
pp. 4287-4292 ◽  
Author(s):  
Marvin C. Gershengorn ◽  
Susanne Neumann
Keyword(s):  
Thyroid Function ◽  
Small Molecule ◽  
Physiological Role ◽  
Tsh Receptor ◽  
Thyroid Tumors ◽  
Inverse Agonists ◽  
Small Molecule Drug ◽  
Pathological Conditions ◽  
Receptor Agonists And Antagonists

The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands.

Quantitative analysis of aldosterone's role in potassium regulation

1988 ◽  
Vol 255 (5) ◽  
pp. F811-F822 ◽  
Author(s):  
D. B. Young
Keyword(s):  
Quantitative Analysis ◽  
Renal Excretion ◽  
Potassium Concentration ◽  
Physiological Role ◽  
Plasma Potassium ◽  
The Body ◽  
Pharmacological Interventions ◽  
Pathological Conditions ◽  
Potassium Regulation

Aldosterone is part of a complex system that regulates plasma potassium concentration by affecting the renal excretion of the ion as well as its distribution within the body. Because there are other components of the system, it has been difficult to determine the physiological significance of aldosterone in potassium regulation by attempting to study the hormone's effects in isolation. In this presentation a quantitative analysis of the potassium control system is used to provide information concerning the physiological role of aldosterone in potassium regulation under normal and pathological conditions, as well as during pharmacological interventions.

Luminal glucose concentrations in the gut under normal conditions

1990 ◽  
Vol 259 (5) ◽  
pp. G822-G837 ◽  
Author(s):  
R. P. Ferraris ◽  
S. Yasharpour ◽  
K. C. Lloyd ◽  
R. Mirzayan ◽  
J. M. Diamond
Keyword(s):  
Absorptive Capacity ◽  
Physiological Role ◽  
Solvent Drag ◽  
Direct Infusion ◽  
Rat Stomach ◽  
Osmotic Water ◽  
Major Mode ◽  
The Face ◽  
Very High

Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.

scholarly journals Cloning of the Malic Enzyme Gene fromCorynebacterium glutamicum and Role of the Enzyme in Lactate Metabolism

2000 ◽  
Vol 66 (7) ◽  
pp. 2981-2987 ◽  
Author(s):  
Pierre Gourdon ◽  
Marie-France Baucher ◽  
Nic D. Lindley ◽  
Armel Guyonvarch
Keyword(s):  
Exponential Growth ◽  
Malic Enzyme ◽  
Tricarboxylic Acid Cycle ◽  
Physiological Role ◽  
Growth Period ◽  
Biochemical Properties ◽  
Lactate Metabolism ◽  
Wild Type ◽  
Malic Enzyme Gene

ABSTRACT Malic enzyme is one of at least five enzymes, known to be present in Corynebacterium glutamicum, capable of carboxylation and decarboxylation reactions coupling glycolysis and the tricarboxylic acid cycle. To date, no information is available concerning the physiological role of the malic enzyme in this bacterium. ThemalE gene from C. glutamicum has been cloned and sequenced. The protein encoded by this gene has been purified to homogeneity, and the biochemical properties have been established. Biochemical characteristics indicate a decarboxylation role linked to NADPH generation. Strains of C. glutamicum in which themalE gene had been disrupted or overexpressed showed no detectable phenotype during growth on either acetate or glucose, but showed a significant modification of growth behavior during lactate metabolism. The wild type showed a characteristic brief period of exponential growth on lactate followed by a linear growth period. This growth pattern was further accentuated in a malE-disrupted strain (ΔmalE). However, the strain overexpressingmalE maintained exponential growth until all lactate had been consumed. This strain accumulated significantly larger amounts of pyruvate in the medium than the other strains.

scholarly journals Altered GABA Signaling in Early Life Epilepsies

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Stephen W. Briggs ◽  
Aristea S. Galanopoulou
Keyword(s):  
Brain Function ◽  
Therapeutic Potential ◽  
Physiological Role ◽  
Neuronal Morphology ◽  
Normal Brain ◽  
Pathological Conditions ◽  
Neurodevelopmental Deficits ◽  
The Brain ◽  
Normal Brain Development

The incidence of seizures is particularly high in the early ages of life. The immaturity of inhibitory systems, such as GABA, during normal brain development and its further dysregulation under pathological conditions that predispose to seizures have been speculated to play a major role in facilitating seizures. Seizures can further impair or disrupt GABAAsignaling by reshuffling the subunit composition of its receptors or causing aberrant reappearance of depolarizing or hyperpolarizing GABAAreceptor currents. Such effects may not result in epileptogenesis as frequently as they do in adults. Given the central role of GABAAsignaling in brain function and development, perturbation of its physiological role may interfere with neuronal morphology, differentiation, and connectivity, manifesting as cognitive or neurodevelopmental deficits. The current GABAergic antiepileptic drugs, while often effective for adults, are not always capable of stopping seizures and preventing their sequelae in neonates. Recent studies have explored the therapeutic potential of chloride cotransporter inhibitors, such as bumetanide, as adjunctive therapies of neonatal seizures. However, more needs to be known so as to develop therapies capable of stopping seizures while preserving the age- and sex-appropriate development of the brain.

scholarly journals The role of exosomes in the mechanisms of inflammation development in patients with cardiovascular pathology and the contribution to therapeutic potential of stem cells

2021 ◽  
Vol 23 (4) ◽  
pp. 566-574
Author(s):  
P. F. Muzychenko ◽  
Zh. M. Minchenko ◽  
T. I. Havrylenko ◽  
V. A. Cherniak ◽  
S. V. Demidov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cellular Therapy ◽  
Therapeutic Potential ◽  
Molecular Genetic ◽  
Physiological Role ◽  
Functional Restoration ◽  
Cardiovascular Pathology ◽  
Inflammatory Reactions ◽  
Pathological Conditions

The aim – based on the analysis of the scientific literature focused on understanding the role of exosomes in the mechanisms of inflammation development and application of stem cells for cellular therapy in different pathological conditions, to identify and substantiate the prospects of using the exosomes as prognostic markers of a disease progression and application of their therapeutic potential in cardiovascular pathology. Global trends in the study of stem cells of different origins from the perspective of morphofunctional, molecular-genetic, cytogenetic, immunogenetic and cytological characteristics contribute significantly the development of regenerative medicine in the context of developing new methodological solutions for the use of stem cells and their components, particularly exosomes, for cell therapy of various pathological conditions. Studies show the indirect effect of exosomes on the immune response activation, coordination of cellular senescence processes and antigen presentation. There are also evidence of their impact on the structural and functional restoration of affected organs and blood vessels. The application potential of exosomes in practical medicine, particularly in the area of new approaches development to synthesize the newer biopharmaceuticals and as markers of multifactorial pathology course in conjunction with studies on the mechanisms of exosome involvement into immune processes is discussed. The study on the exosome-mediated mechanisms of inflammation in atherosclerosis is relevant, given the fact that their main physiological role is to implement the link between immunocompetent cells. Conclusions. Improving knowledge of the molecular biological mechanisms of the exosome influence on immunological processes in patients with cardiovascular pathology allows to expand the range of diagnostic and prognostic criteria for the formation of immuno-inflammatory reactions and endothelial dysfunction and to outline ways to personify the choice of therapeutic programs, which, in turn, can open approaches to develop fundamentally newer pharmaceuticals.

scholarly journals Enzymatically Produced Trimethylamine N-Oxide: Conserving It or Eliminating It

Catalysts ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1028 ◽  
Author(s):  
Gianluca Catucci ◽  
Giulia Querio ◽  
Sheila J. Sadeghi ◽  
Gianfranco Gilardi ◽  
Renzo Levi
Keyword(s):  
Marine Mammals ◽  
Hydrostatic Stress ◽  
Physiological Role ◽  
Health Conditions ◽  
Renal Diseases ◽  
Drug Metabolizing Enzyme ◽  
Long Time ◽  
Metabolizing Enzyme ◽  
Very High

Trimethylamine N-Oxide (TMAO) is the product of the monooxygenation reaction catalyzed by a drug-metabolizing enzyme, human flavin-containing monooxygenase 3 (hFMO3), and its animal orthologues. For several years, researchers have looked at TMAO and hFMO3 as two distinct molecules playing specific but separate roles, the former to defend saltwater animals from osmotic or hydrostatic stress and the latter to process xenobiotics in men. The presence of high levels of plasmatic TMAO in elasmobranchs and other animals was demonstrated a long time ago, whereas the actual physiological role of hFMO3 is still unknown because the enzyme has been mainly characterized for its ability to oxidize drugs. Recently TMAO was found to be related to several human health conditions such as atherosclerosis, cardiovascular, and renal diseases. This correlation poses a striking question of how other vertebrates (and invertebrates) can survive in the presence of very high TMAO concentrations (micromolar in humans, millimolar in marine mammals and several hundred millimolar in elasmobranchs). Therefore, it is important to address how TMAO, its precursors, and FMO catalytic activity are interconnected.

ASCT1 and ASCT2: Brother and Sister?

2021 ◽  
pp. 247255522110302
Author(s):  
Mariafrancesca Scalise ◽  
Lara Console ◽  
Jessica Cosco ◽  
Lorena Pochini ◽  
Michele Galluccio ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Physiological Role ◽  
Cell Plasma Membrane ◽  
Substrate Specificities ◽  
High Affinity ◽  
Regulatory Aspects ◽  
Pathological Conditions ◽  
Cell Plasma ◽  
3D Architecture

The SLC1 family includes seven members divided into two groups, namely, EAATs and ASCTs, that share similar 3D architecture; the first one includes high-affinity glutamate transporters, and the second one includes SLC1A4 and SLC1A5, known as ASCT1 and ASCT2, respectively, responsible for the traffic of neutral amino acids across the cell plasma membrane. The physiological role of ASCT1 and ASCT2 has been investigated over the years, revealing different properties in terms of substrate specificities, affinities, and regulation by physiological effectors and posttranslational modifications. Furthermore, ASCT1 and ASCT2 are involved in pathological conditions, such as neurodegenerative disorders and cancer. This has driven research in the pharmaceutical field aimed to find drugs able to target the two proteins. This review focuses on structural, functional, and regulatory aspects of ASCT1 and ASCT2, highlighting similarities and differences.

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