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.

scholarly journals CHITINASE-LIKE PROTEINS AS PROMISING MARKERS IN CANCER PATIENTS

2018 ◽  
Vol 17 (4) ◽  
pp. 99-105 ◽  
Author(s):  
I. V. Larionova ◽  
T. N. Sevastyanova ◽  
A. A. Rakina ◽  
N. V. Cherdyntseva ◽  
Ju. G. Kzhyshkowska
Keyword(s):  
Growth Factors ◽  
Cancer Patient ◽  
Cancer Patients ◽  
Inflammatory Diseases ◽  
Tumour Progression ◽  
Patient Benefit ◽  
Pathological Conditions ◽  
The Family ◽  
Metastasis Development

In the present review we collected the main studies regarding the role of chitinase-like proteins (CLPs), belonging to the family of Glyco_18 domain-containing proteins, in different cancers. In  humans, 3 chitinaselike proteins have been identified: YKL-40 (CHI3L1), YKL-39 (CHI3L2) and  stabilin-1-interacting chitinase-like protein (SI-CLP). CLPs are produced by several types of cells  and combine the properties of cytokines and growth factors. The high levels of CLPs were  identified in the circulation of the patients with inflammatory diseases and various types of  tumors. We highlighted the main known functions of CLPs in normal and pathological conditions, their contribution to metastasis development, angiogenesis, invasion and other processes in  cancer, the correlation of the levels of CLPs with tumour progression. Our data also contribute to the understanding of question how CLP could be useful for cancer patient benefit.

The Effects on Angiogenesis of Relevant Inorganic Chemotherapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Tiziano Marzo ◽  
Diego La Mendola
Keyword(s):  
Metal Ions ◽  
Anticancer Agents ◽  
Review Article ◽  
Pharmacological Effects ◽  
Complex Interactions ◽  
Pathological Conditions ◽  
Copper Zinc ◽  
Antiangiogenic Factors ◽  
The Impact

: Angiogenesis is a key process allowing the formation of blood vessels. It is crucial for all the tissue and organs, ensuring their function and growth. Angiogenesis is finely controlled by several mechanisms involving complex interactions between pro- or antiangiogenic factors and an imbalance in this control chain may result in pathological conditions. Metals as copper, zinc and iron cover an essential role in regulating angiogenesis, thus therapies having physiological metals as target have been proposed. Also, some complexes of heavier metal ions (e.g Pt, Au, Ru) are currently used as established or experimental anticancer agents targeting genomic or non-genomic targets. These molecules may affect the angiogenic mechanisms determining different effects that have been only poorly and non-systematically investigated so far. Accordingly, in this review article we aim to recapitulate the impact on the angiogenic process of some reference anticancer drugs, and how it is connected to the overall pharmacological effects. Also, we highlight how the activity of these drugs can be related to the role of biological essential metal ions. Overall, this may allow a deeper description and understanding of the antineoplastic activity of both approved or experimental metal complexes, providing important insights for the synthesis of new inorganic drugs able to overcome resistance and recurrence phenomena.

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.

scholarly journals Role of ERLINs in the Control of Cell Fate through Lipid Rafts

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2408
Author(s):  
Valeria Manganelli ◽  
Agostina Longo ◽  
Vincenzo Mattei ◽  
Serena Recalchi ◽  
Gloria Riitano ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Fate ◽  
Lipid Raft ◽  
Protein Markers ◽  
Ip3 Receptors ◽  
Pathological Conditions ◽  
The Family ◽  
Inositol 1,4,5 Trisphosphate ◽  
And Function

ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP3) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the “interchange” between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases.

scholarly journals Business Entrepreneurship And Education

2021 ◽  
Vol 17 (33) ◽  
pp. 211-224
Author(s):  
Pedro Álvaro Correia Pereira ◽  
Irene García Medina ◽  
Patricia Margarida Farias Coelho
Keyword(s):  
Skills Acquisition ◽  
Review Of The Literature ◽  
Endogenous Factors ◽  
Factors Affecting ◽  
Individual Motivation ◽  
Self Employment ◽  
The Social ◽  
The Family ◽  
The Creation

This study is a review of the literature regarding business entrepreneurship and education. The main aim is to study the social and educational factors affecting the creation of self-employment for young people as a contribution to the development of local entrepreneurship, reducing unemployment and leveraging economic development. Of the various social influencers, it was important to understand the role of the family, especially of the parents, in motivating and sustaining the creation of one's own job and in the actions of entrepreneurship. In the same sense, at the educational level, to perceive the consequences of access to new resources that expand and support knowledge and skills acquisition useful for creating one's own job and reducing risk aversion of business activities. Finally, to understand the role of endogenous factors such as intelligence and individual motivation in the pursuit of entrepreneurship activities and their relationship with social and educational influencers.

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.

scholarly journals Characterization of two myostatin genes in pufferfish Takifugu bimaculatus: sequence, genomic structure, and expression

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9655
Author(s):  
Yinzhen Sheng ◽  
Yulong Sun ◽  
Xin Zhang ◽  
Haifu Wan ◽  
Chengjie Yao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Genomic Structure ◽  
Muscle Growth ◽  
Negative Regulator ◽  
Pigment Formation ◽  
Formation Stage ◽  
Proliferation And Differentiation ◽  
The Brain

Myostatin (MSTN) is a negative regulator of muscle growth, which restrains the proliferation and differentiation of myoblasts. To understand the role of two mstn genes of Takifugu bimaculatus, the full-length cDNAs of 1131 bp Tbmstn1 and 1,080 bp Tbmstn2 were obtained from the T. bimaculatus’ genomic database, which encodes 376 and 359 amino acids, respectively. The results of qRT-PCR showed that Tbmstn1 was expressed in the eye, kidney, spleen, skeletal muscle, gill, and brain, and the expression level in the skeletal muscle was extremely significantly higher than in other examined tissues. Tbmstn2 was expressed in the skin, skeletal muscle, gill, and brain, and had the highest expression in the skeletal muscle, followed by expression in the brain. Meanwhile, in different stages of embryonic development, the expression of Tbmstn1 started from the gastrula stage. Its expression in the eye-pigment formation stage and hatching stage was significantly higher than that in other stages. The Tbmstn2 was expressed in all examined embryonic stages with different levels, and the highest expression was detected in the eye-pigment formation stage. These results suggested that Tbmstn1 and Tbmstn2 may involve in the development of skeletal muscle, and Tbmstn2 may be related to the formation of nervous system.

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 Microarray and Functional Gene Analyses of Sulfate-Reducing Prokaryotes in Low-Sulfate, Acidic Fens Reveal Cooccurrence of Recognized Genera and Novel Lineages

2004 ◽  
Vol 70 (12) ◽  
pp. 6998-7009 ◽  
Author(s):  
Alexander Loy ◽  
Kirsten Küsel ◽  
Angelika Lehner ◽  
Harold L. Drake ◽  
Michael Wagner
Keyword(s):  
16S Rrna ◽  
Soil Solution ◽  
Rrna Gene ◽  
Sulfate Reducing ◽  
Physiological Properties ◽  
The Family ◽  
Acidic Conditions ◽  
Microarray Analyses

ABSTRACT Low-sulfate, acidic (approximately pH 4) fens in the Lehstenbach catchment in the Fichtelgebirge mountains in Germany are unusual habitats for sulfate-reducing prokaryotes (SRPs) that have been postulated to facilitate the retention of sulfur and protons in these ecosystems. Despite the low in situ availability of sulfate (concentration in the soil solution, 20 to 200 μM) and the acidic conditions (soil and soil solution pHs, approximately 4 and 5, respectively), the upper peat layers of the soils from two fens (Schlöppnerbrunnen I and II) of this catchment displayed significant sulfate-reducing capacities. 16S rRNA gene-based oligonucleotide microarray analyses revealed stable diversity patterns for recognized SRPs in the upper 30 cm of both fens. Members of the family “Syntrophobacteraceae” were detected in both fens, while signals specific for the genus Desulfomonile were observed only in soils from Schlöppnerbrunnen I. These results were confirmed and extended by comparative analyses of environmentally retrieved 16S rRNA and dissimilatory (bi)sulfite reductase (dsrAB) gene sequences; dsrAB sequences from Desulfobacca-like SRPs, which were not identified by microarray analysis, were obtained from both fens. Hypotheses concerning the ecophysiological role of these three SRP groups in the fens were formulated based on the known physiological properties of their cultured relatives. In addition to these recognized SRP lineages, six novel dsrAB types that were phylogenetically unrelated to all known SRPs were detected in the fens. These dsrAB sequences had no features indicative of pseudogenes and likely represent novel, deeply branching, sulfate- or sulfite-reducing prokaryotes that are specialized colonists of low-sulfate habitats.

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