scholarly journals Peptides contained in the composition of Laennec that contribute to the treatment of hyperferritinemia and iron overload disorders

2021 ◽  
Vol 13 (4) ◽  
pp. 413-425
Author(s):  
O. A. Gromova ◽  
I. Yu. Torshin ◽  
V. A. Maksimov ◽  
A. G. Chuchalin ◽  
V. G. Zgoda ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Big Data ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Immunomodulatory Effects ◽  
Topological Approach ◽  
Pathologic Condition ◽  
Modern Methods ◽  
Iron Deposits

Introduction. Hemosiderosis is a pathologic condition that accompanies liver, lung, and other organ diseases. Polypeptide-containing drug Laennec contributes to the elimination of excessive iron deposits in tissues.Aim. The study was aimed to identify peptides contained in the composition of the drug that take part in the regulation of iron homeostasis and correction of hemosiderosis and hyperferritinemia.Materials and Methods. The study of the drug composition was conducted with hybrid mass-spectrometry and modern methods of analysis of Big Data based on the topological approach to recognition.Results. The preparation contains 19 peptides that are potentially important for the regulation of iron homeostasis. These peptides help to treat the disorders of iron metabolism by regulating the levels of the main hormone of iron homeostasis hepcidin by reducing the synthesis of ferritin and by exhibiting anti-inflammatory and immunomodulatory effects.Conclusion. The identified peptides allowed the authors to describe the molecular mechanisms of the iron overload elimination that are known from experimental and clinical studies of the analyzed polypeptide drug.

scholarly journals Molecular Mechanisms Regulating Hepcidin Revealed by Hepcidin Disorders

2011 ◽  
Vol 11 ◽  
pp. 1357-1366 ◽  
Author(s):  
Clara Camaschella ◽  
Laura Silvestri
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Transcriptional Control ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Human Life ◽  
Genetic Diseases ◽  
The Body ◽  
Deficiency Anemia ◽  
Iron Regulatory Proteins

Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (iron-refractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders.

scholarly journals Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Akram Bardestani ◽  
Shiva Ebrahimpour ◽  
Ali Esmaeili ◽  
Abolghasem Esmaeili
Keyword(s):  
Iron Oxide ◽  
Iron Overload ◽  
Protein Aggregation ◽  
Iron Oxide Nanoparticles ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Radical Scavenging ◽  
Prolonged Treatment ◽  
Oxide Nanoparticles ◽  
Neuroprotective Effects

AbstractIron oxide nanoparticles (IONPs) have been proposed as targeted carriers to deliver therapeutic molecules in the central nervous system (CNS). However, IONPs may damage neural tissue via free iron accumulation, protein aggregation, and oxidative stress. Neuroprotective effects of quercetin (QC) have been proven due to its antioxidant and anti-inflammatory properties. However, poor solubility and low bioavailability of QC have also led researchers to make various QC-involved nanoparticles to overcome these limitations. We wondered how high doses or prolonged treatment with quercetin conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) could improve cognitive dysfunction and promote neurogenesis without any toxicity. It can be explained that the QC inhibits protein aggregation and acts against iron overload via iron-chelating activity, iron homeostasis genes regulation, radical scavenging, and attenuation of Fenton/Haber–Weiss reaction. In this review, first, we present brain iron homeostasis, molecular mechanisms of iron overload that induced neurotoxicity, and the role of iron in dementia-associated diseases. Then by providing evidence of IONPs neurotoxicity, we discuss how QC neutralizes IONPs neurotoxicity, and finally, we make a brief comparison between QC and conventional iron chelators. In this review, we highlight that QC as supplementation and especially in conjugated form reduces iron oxide nanoparticles neurotoxicity in clinical application.

scholarly journals Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis

2019 ◽  
Vol 216 (4) ◽  
pp. 950-965 ◽  
Author(s):  
Yoshiharu Muto ◽  
Toshiro Moroishi ◽  
Kazuya Ichihara ◽  
Masaaki Nishiyama ◽  
Hideyuki Shimizu ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Genetically Engineered ◽  
Liver Carcinogenesis ◽  
Cellular Iron ◽  
Hepatic Iron Overload ◽  
Genetically Engineered Mouse Model ◽  
Compensatory Proliferation ◽  
Cellular Iron Homeostasis

Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.

A Mucin-Specific Protease Enables Molecular and Functional Analysis of Human Cancer-Associated Mucins

2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
High Resolution Mass Spectrometry ◽  
Human Cancer ◽  
Glycosylation Sites ◽  
Bacterial Protease ◽  
Specific Protease ◽  
To Come ◽  
And Function

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>

scholarly journals The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance

2021 ◽  
Vol 22 (4) ◽  
pp. 2204
Author(s):  
Simon Grootendorst ◽  
Jonathan de Wilde ◽  
Birgit van Dooijeweert ◽  
Annelies van Vuren ◽  
Wouter van Solinge ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Significant Problem ◽  
Blood Transfusions ◽  
Intrinsic Defects ◽  
Chronic Anemia ◽  
Erythroid Development ◽  
Disease Specific

Rare hereditary anemias (RHA) represent a group of disorders characterized by either impaired production of erythrocytes or decreased survival (i.e., hemolysis). In RHA, the regulation of iron metabolism and erythropoiesis is often disturbed, leading to iron overload or worsening of chronic anemia due to unavailability of iron for erythropoiesis. Whereas iron overload generally is a well-recognized complication in patients requiring regular blood transfusions, it is also a significant problem in a large proportion of patients with RHA that are not transfusion dependent. This indicates that RHA share disease-specific defects in erythroid development that are linked to intrinsic defects in iron metabolism. In this review, we discuss the key regulators involved in the interplay between iron and erythropoiesis and their importance in the spectrum of RHA.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals EnvIRONmental Aspects in Myelodysplastic Syndrome

2021 ◽  
Vol 22 (10) ◽  
pp. 5202
Author(s):  
Verena Petzer ◽  
Igor Theurl ◽  
Günter Weiss ◽  
Dominik Wolf
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Clonal Evolution ◽  
Red Blood Cell Transfusion ◽  
Bone Marrow Niche ◽  
Environmental Aspects ◽  
Complete Understanding ◽  
Mediated Effects ◽  
Important Player

Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red blood cell transfusion represent the main underlying reasons. However, like the genetic heterogeneity of MDS, iron homeostasis is also diverse in different MDS subtypes and can no longer be generalized. While a certain amount of iron and reactive oxygen species (ROS) are indispensable for proper hematological output, both are harmful if present in excess. Consequently, iron overload has been increasingly recognized as an important player in MDS, which is worth paying attention to. This review focuses on iron- and ROS-mediated effects in the bone marrow niche, their implications for hematopoiesis and their yet unclear involvement in clonal evolution. Moreover, we provide recent insights into hepcidin regulation in MDS and its interaction between erythropoiesis and inflammation. Based on Tet methylcytosine dioxygenase 2 (TET2), representing one of the most frequently mutated genes in MDS, leading to disturbances in both iron homeostasis and hematopoiesis, we highlight that different genetic alteration may have different implications and that a comprehensive workup is needed for a complete understanding and development of future therapies.

scholarly journals 3D-surface MALDI mass spectrometry imaging for visualising plant defensive cardiac glycosides in Asclepias curassavica

2021 ◽  
Vol 413 (8) ◽  
pp. 2125-2134
Author(s):  
Domenic Dreisbach ◽  
Georg Petschenka ◽  
Bernhard Spengler ◽  
Dhaka R. Bhandari
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Cardiac Glycosides ◽  
Molecular Mechanisms ◽  
Plant Science ◽  
Primary Metabolism ◽  
Native Plant ◽  
Asclepias Curassavica ◽  
3D Surface ◽  
3D Surfaces

AbstractMass spectrometry–based imaging (MSI) has emerged as a promising method for spatial metabolomics in plant science. Several ionisation techniques have shown great potential for the spatially resolved analysis of metabolites in plant tissue. However, limitations in technology and methodology limited the molecular information for irregular 3D surfaces with resolutions on the micrometre scale. Here, we used atmospheric-pressure 3D-surface matrix-assisted laser desorption/ionisation mass spectrometry imaging (3D-surface MALDI MSI) to investigate plant chemical defence at the topographic molecular level for the model system Asclepias curassavica. Upon mechanical damage (simulating herbivore attacks) of native A. curassavica leaves, the surface of the leaves varies up to 700 μm, and cardiac glycosides (cardenolides) and other defence metabolites were exclusively detected in damaged leaf tissue but not in different regions of the same leaf. Our results indicated an increased latex flow rate towards the point of damage leading to an accumulation of defence substances in the affected area. While the concentration of cardiac glycosides showed no differences between 10 and 300 min after wounding, cardiac glycosides decreased after 24 h. The employed autofocusing AP-SMALDI MSI system provides a significant technological advancement for the visualisation of individual molecule species on irregular 3D surfaces such as native plant leaves. Our study demonstrates the enormous potential of this method in the field of plant science including primary metabolism and molecular mechanisms of plant responses to abiotic and biotic stress and symbiotic relationships. Graphical abstract

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