scholarly journals The Close Relationship between the Golgi Trafficking Machinery and Protein Glycosylation

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2652
Author(s):  
Anna Frappaolo ◽  
Angela Karimpour-Ghahnavieh ◽  
Stefano Sechi ◽  
Maria Grazia Giansanti
Keyword(s):  
Inflammatory Diseases ◽  
Vesicle Trafficking ◽  
Protein Glycosylation ◽  
Post Translational Modification ◽  
Pathological Conditions ◽  
Close Relationship ◽  
Secretory Transport ◽  
Molecular Machinery ◽  
Correct Location ◽  
Glycoprotein Glycosylation

Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of glycosylation, inflammatory diseases and cancer. Glycoprotein glycosylation at the Golgi involves the coordinated action of hundreds of glycosyltransferases and glycosidases, which are maintained at the correct location through retrograde vesicle trafficking between Golgi cisternae. In this review, we describe the molecular machinery involved in vesicle trafficking and tethering at the Golgi apparatus and the effects of mutations in the context of glycan biosynthesis and human diseases.

scholarly journals Protein Glycosylation Investigated by Mass Spectrometry: An Overview

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1986
Author(s):  
Anna Illiano ◽  
Gabriella Pinto ◽  
Chiara Melchiorre ◽  
Andrea Carpentieri ◽  
Vincenza Faraco ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Trafficking ◽  
Inflammatory Diseases ◽  
Protein Glycosylation ◽  
Qualitative And Quantitative Analysis ◽  
Post Translational Modification ◽  
Cellular Mechanisms ◽  
Disease States ◽  
Recognition Protein ◽  
The Individual

The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms.

scholarly journals The Utility of Iron Chelators in the Management of Inflammatory Disorders

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
C. Lehmann ◽  
S. Islam ◽  
S. Jarosch ◽  
J. Zhou ◽  
D. Hoskin ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Iron Chelation ◽  
Iron Regulation ◽  
Human Organism ◽  
Iron Availability ◽  
Pathological Conditions ◽  
Reasonable Approach ◽  
Potential Impact ◽  
Pharmaceutical Agents

Since iron can contribute to detrimental radical generating processes through the Fenton and Haber-Weiss reactions, it seems to be a reasonable approach to modulate iron-related pathways in inflammation. In the human organism a counterregulatory reduction in iron availability is observed during inflammatory diseases. Under pathological conditions with reduced or increased baseline iron levels different consequences regarding protection or susceptibility to inflammation have to be considered. Given the role of iron in development of inflammatory diseases, pharmaceutical agents targeting this pathway promise to improve the clinical outcome. The objective of this review is to highlight the mechanisms of iron regulation and iron chelation, and to demonstrate the potential impact of this strategy in the management of several acute and chronic inflammatory diseases, including cancer.

Vesicle Trafficking, Autophagy and Nanoparticles: A Brief Review

2020 ◽  
Vol 10 (1) ◽  
pp. 3-19
Author(s):  
Tianzhong Li ◽  
Mengsu Yang
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Cellular Uptake ◽  
Vesicle Trafficking ◽  
Endocytic Pathway ◽  
Proton Sponge ◽  
Intracellular Release ◽  
Molecular Machinery ◽  
Delivery Vehicles ◽  
Selection Of

Background: Nanomedicine shows a huge promise for incurable diseases. So far, more than 50 nanoparticles have been approved by FDA and around 80 nanoformulations are currently in clinical trials. Nanoparticles possess several advantages over traditional drugs, including higher biocompatibility and bioavailability. One of the challenges for their wide application is insufficient understanding of the molecular network related to internalization of particles and intracellular release of cargos. Objective: This article aims to review the interactions between nanoparticles, vesicle transportation and autophagy pathways. The underlying molecular machinery is also discussed. Methods: For each step of the vesicle trafficking and autophagy, details of signaling pathways are described for a better understanding of the interactions between delivery vehicles and biomolecules within the cell. Conclusion: The selection of cellular uptake route mainly depends on physical characteristics of nanoparticles. For nanoparticles modified with ligands, they undergo receptormediated endocytic pathway. Once residing within the cells, cargos are released after disruption of endosomes, a mechanism called ‘proton sponge effect’. Besides, internalized nanoparticles either can be exocytosized, or they initiate the autophagy response, affecting the intracellular distribution of drugs.

scholarly journals Sialylated Immunoglobulins for the Treatment of Immuno-Inflammatory Diseases

2020 ◽  
Vol 21 (15) ◽  
pp. 5472
Author(s):  
Yuliya V. Markina ◽  
Elena V. Gerasimova ◽  
Alexander M. Markin ◽  
Victor Y. Glanz ◽  
Wei-Kai Wu ◽  
...  
Keyword(s):  
Single Molecule ◽  
Inflammatory Diseases ◽  
Effector Proteins ◽  
Molecular Structures ◽  
Common Mechanism ◽  
Post Translational Modification ◽  
Effector Functions ◽  
Humoral Immune ◽  
Inflammatory Action

Immunoglobulins are the potent effector proteins of the humoral immune response. In the course of evolution, immunoglobulins have formed extremely diverse types of molecular structures with antigen-recognizing, antigen-binding, and effector functions embedded in a single molecule. Polysaccharide moiety of immunoglobulins plays the essential role in immunoglobulin functioning. There is growing evidence that the carbohydrate composition of immunoglobulin-linked glycans, and especially their terminal sialic acid residues, provide a key effect on the effector functions of immunoglobulins. Possibly, sialylation of Fc glycan is a common mechanism of IgG anti-inflammatory action in vivo. Thus, the post-translational modification (glycosylation) of immunoglobulins opens up significant possibilities in the diagnosis of both immunological and inflammatory disorders and in their therapies. This review is focused on the analysis of glycosylation of immunoglobulins, which can be a promising addition to improve existing strategies for the diagnosis and treatment of various immuno-inflammatory diseases.

scholarly journals Modulation of Autophagy for Controlling Immunity

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 138 ◽  
Author(s):  
Young Jin Jang ◽  
Jae Hwan Kim ◽  
Sanguine Byun
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Innate And Adaptive Immunity ◽  
Pathological Conditions ◽  
Physiological Homeostasis ◽  
Autophagy Pathway ◽  
Key Steps ◽  
Additional Role

Autophagy is an essential process that maintains physiological homeostasis by promoting the transfer of cytoplasmic constituents to autophagolysosomes for degradation. In immune cells, the autophagy pathway plays an additional role in facilitating proper immunological functions. Specifically, the autophagy pathway can participate in controlling key steps in innate and adaptive immunity. Accordingly, alterations in autophagy have been linked to inflammatory diseases and defective immune responses against pathogens. In this review, we discuss the various roles of autophagy signaling in coordinating immune responses and how these activities are connected to pathological conditions. We highlight the therapeutic potential of autophagy modulators that can impact immune responses and the mechanisms of action responsible.

scholarly journals Tight Junction in the Intestinal Epithelium: Its Association with Diseases and Regulation by Phytochemicals

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Bonggi Lee ◽  
Kyoung Mi Moon ◽  
Choon Young Kim
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Intestinal Epithelium ◽  
Essential Role ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Nutritional Factors ◽  
Nutritional Interventions ◽  
Intestinal Epithelia ◽  
Pathological Conditions

The intestine plays an essential role in integrating immunity and nutrient digestion and absorption. Adjacent intestinal epithelia form tight junctions (TJs) that are essential to the function of the physical intestinal barrier, regulating the paracellular movement of various substances including ions, solutes, and water across the intestinal epithelium. Studies have shown that TJ dysfunction is highly associated with metabolic and inflammatory diseases. Thus, molecular and nutritional factors that improve TJ activity have gained attention in the pharmaceutical and medicinal fields. This review focuses on the association between TJ and diverse pathological conditions, as well as various molecular and nutritional interventions designed to boost TJ integrity.

scholarly journals Iron and Sphingolipids as Common Players of (Mal)Adaptation to Hypoxia in Pulmonary Diseases

2020 ◽  
Vol 21 (1) ◽  
pp. 307 ◽  
Author(s):  
Sara Ottolenghi ◽  
Aida Zulueta ◽  
Anna Caretti
Keyword(s):  
High Altitude ◽  
Inflammatory Diseases ◽  
Physiological Adaptation ◽  
Adaptation To Hypoxia ◽  
Chronic Obstructive ◽  
Compensatory Response ◽  
Obstructive Pulmonary Disease ◽  
Pathological Conditions ◽  
High Altitude Pulmonary Edema ◽  
Sphingosine 1 Phosphate

Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological conditions (respiratory diseases). In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and Cystic Fibrosis (CF) as examples of maladaptation to hypoxia, and highlight some of the potential mechanisms influencing the prognosis of the affected patients. Among the specific pathways modulated in response to hypoxia, iron metabolism has been widely explored in recent years. Recent evidence emphasizes hepcidin as highly involved in the compensatory response to hypoxia in healthy subjects. A less investigated field in the adaptation to hypoxia is the sphingolipid (SPL) metabolism, especially through Ceramide and sphingosine 1 phosphate. Both individually and in concert, iron and SPL are active players of the (mal)adaptation to physiological hypoxia, which can result in the pathological HAPE. Our aim is to identify some pathways and/or markers involved in the physiological adaptation to low atmospheric pressures (high altitudes) that could be involved in pathological adaptation to hypoxia as it occurs in pulmonary inflammatory diseases. Hepcidin, Cer, S1P, and their interplay in hypoxia are raising growing interest both as prognostic factors and therapeutical targets.

scholarly journals The impact of O-glycan chemistry on the stability of intrinsically disordered proteins

2018 ◽  
Vol 9 (15) ◽  
pp. 3710-3715 ◽  
Author(s):  
Erica T. Prates ◽  
Xiaoyang Guan ◽  
Yaohao Li ◽  
Xinfeng Wang ◽  
Patrick K. Chaffey ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Protein Glycosylation ◽  
Disordered Proteins ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
P Protein ◽  
The Stability ◽  
The Impact

Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.

scholarly journals N- and O-Glycosylation Pathways in the Microalgae Polyphyletic Group

2020 ◽  
Vol 11 ◽  
Author(s):  
Elodie Mathieu-Rivet ◽  
Narimane Mati-Baouche ◽  
Marie-Laure Walet-Balieu ◽  
Patrice Lerouge ◽  
Muriel Bardor
Keyword(s):  
Recombinant Proteins ◽  
Metabolic Pathways ◽  
Phylogenetic Diversity ◽  
State Of The Art ◽  
Protein Glycosylation ◽  
Expression Systems ◽  
Post Translational Modification ◽  
Photosynthetic Organisms ◽  
Biological Features ◽  
Heterologous Expression Systems

The term microalga refers to various unicellular and photosynthetic organisms representing a polyphyletic group. It gathers numerous species, which can be found in cyanobacteria (i.e., Arthrospira) as well as in distinct eukaryotic groups, such as Chlorophytes (i.e., Chlamydomonas or Chlorella) and Heterokonts (i.e., diatoms). This phylogenetic diversity results in an extraordinary variety of metabolic pathways, offering large possibilities for the production of natural compounds like pigments or lipids that can explain the ever-growing interest of industrials for these organisms since the middle of the last century. More recently, several species have received particular attention as biofactories for the production of recombinant proteins. Indeed, microalgae are easy to grow, safe and cheap making them attractive alternatives as heterologous expression systems. In this last scope of applications, the glycosylation capacity of these organisms must be considered as this post-translational modification of proteins impacts their structural and biological features. Although these mechanisms are well known in various Eukaryotes like mammals, plants or insects, only a few studies have been undertaken for the investigation of the protein glycosylation in microalgae. Recently, significant progresses have been made especially regarding protein N-glycosylation, while O-glycosylation remain poorly known. This review aims at summarizing the recent data in order to assess the state-of-the art knowledge in glycosylation processing in microalgae.

scholarly journals Targeting Opposing Immunological Roles of the Junctional Adhesion Molecule-A in Autoimmunity and Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Caio S. Bonilha ◽  
Robert A. Benson ◽  
James M. Brewer ◽  
Paul Garside
Keyword(s):  
Immune Responses ◽  
Adhesion Molecule ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Clinical Pathology ◽  
Surface Adhesion ◽  
Pathological Conditions ◽  
Relevant Role ◽  
A Cell ◽  
Cell Surface Adhesion Molecule

The junctional adhesion molecule-A (JAM-A) is a cell surface adhesion molecule expressed on platelets, epithelial cells, endothelial cells and leukocytes (e. g. monocytes and dendritic cells). JAM-A plays a relevant role in leukocyte trafficking and its therapeutic potential has been studied in several pathological conditions due to its capacity to induce leukocyte migration out of inflamed sites or infiltration into tumor sites. However, disruption of JAM-A pathways may worsen clinical pathology in some cases. As such, the effects of JAM-A manipulation on modulating immune responses in the context of different diseases must be better understood. In this mini-review, we discuss the potential of JAM-A as a therapeutic target, summarizing findings from studies manipulating JAM-A in the context of inflammatory diseases (e.g. autoimmune diseases) and cancer and highlighting described mechanisms.

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