scholarly journals The Potential of Telomeric G-Quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 249 ◽  
Author(s):  
Ekaterina A. Golenkina ◽  
Galina M. Viryasova ◽  
Nina G. Dolinnaya ◽  
Valeria A. Bannikova ◽  
Tatjana V. Gaponova ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Viral Infections ◽  
Uv Spectroscopy ◽  
Human Neutrophils ◽  
First Line ◽  
Cellular Effects ◽  
Cellular Processes ◽  
G Quadruplex ◽  
New Generation

Human neutrophils are the first line of defense against bacterial and viral infections. They eliminate pathogens through phagocytosis, which activate the 5-lipoxygenase (5-LOX) pathway resulting in synthesis of leukotrienes. Using HPLC analysis, flow cytometry, and other biochemical methods, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs) able to fold into G-quadruplex structures on the main functions of neutrophils. Designed ODNs contained four human telomere TTAGGG repeats (G4) including those with phosphorothioate oligoguanosines attached to the end(s) of G-quadruplex core. Just modified analogues of G4 was shown to more actively than parent ODN penetrate into cells, improve phagocytosis of Salmonella typhimurium bacteria, affect 5-LOX activation, the cytosol calcium ion level, and the oxidative status of neutrophils. As evident from CD and UV spectroscopy data, the presence of oligoguanosines flanking G4 sequence leads to dramatic changes in G-quadruplex topology. While G4 folds into a single antiparallel structure, two main folded forms have been identified in solutions of modified ODNs: antiparallel and dominant, more stable parallel. Thus, both the secondary structure of ODNs and their ability to penetrate into the cytoplasm of cells are important for the activation of neutrophil cellular effects. Our results offer new clues for understanding the role of G-quadruplex ligands in regulation of integral cellular processes and for creating the antimicrobial agents of a new generation.

scholarly journals The Presence and Localization of G-Quadruplex Forming Sequences in the Domain of Bacteria

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1711 ◽  
Author(s):  
Martin Bartas ◽  
Michaela Čutová ◽  
Václav Brázda ◽  
Patrik Kaura ◽  
Jiří Šťastný ◽  
...  
Keyword(s):  
Regulatory Sequences ◽  
Bacterial Genomes ◽  
Dna Structures ◽  
Cellular Processes ◽  
G Quadruplex ◽  
Data Point ◽  
Functional Relevance

The role of local DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, the significance of G-quadruplexes was demonstrated in the last decade, and their presence and functional relevance has been demonstrated in many genomes, including humans. In this study, we analyzed the presence and locations of G-quadruplex-forming sequences by G4Hunter in all complete bacterial genomes available in the NCBI database. G-quadruplex-forming sequences were identified in all species, however the frequency differed significantly across evolutionary groups. The highest frequency of G-quadruplex forming sequences was detected in the subgroup Deinococcus-Thermus, and the lowest frequency in Thermotogae. G-quadruplex forming sequences are non-randomly distributed and are favored in various evolutionary groups. G-quadruplex-forming sequences are enriched in ncRNA segments followed by mRNAs. Analyses of surrounding sequences showed G-quadruplex-forming sequences around tRNA and regulatory sequences. These data point to the unique and non-random localization of G-quadruplex-forming sequences in bacterial genomes.

scholarly journals Overview of RNA G-quadruplex structures

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Magdalena Małgowska
Keyword(s):  
Three Dimensional ◽  
Telomere Maintenance ◽  
Structural Studies ◽  
Biological Functions ◽  
Cellular Processes ◽  
Novel Drugs ◽  
G Quadruplex ◽  
Conformational Diversity

G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the three-dimensional structures of G-quadruplexes plays an important role in understanding their conformational diversity, physiological functions, and in the design of novel drugs targeting G-quadruplexes. For the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of RNA G-quadruplexes, based on high-resolution structures, available in RCSB PDB data base and on structural models. In addition, we point out to the current challenges in this field of research.

scholarly journals Role of apoptosis and autophagy in tuberculosis

2017 ◽  
Vol 313 (2) ◽  
pp. L218-L229 ◽  
Author(s):  
Adam Lam ◽  
Rohan Prabhu ◽  
Christine M. Gross ◽  
Lee Ann Riesenberg ◽  
Vinodkumar Singh ◽  
...  
Keyword(s):  
Vital Role ◽  
Host Responses ◽  
First Line ◽  
Active Infection ◽  
Primary Host ◽  
Treatment Regimens ◽  
Cellular Processes ◽  
Systemic Symptoms ◽  
Rich History

Tuberculosis (TB) is one of the oldest known human diseases and is transmitted by the bacteria Mycobacterium tuberculosis (Mtb). TB has a rich history with evidence of TB infections dating back to 5,800 b.c. TB is unique in its ability to remain latent in an individual for decades, with the possibility of later reactivation, causing widespread systemic symptoms. Currently, it is estimated that more than one-third of the world’s population (~2 billion people) are infected with Mtb. Prolonged periods of therapy and complexity of treatment regimens, especially in active infection, have led to poor compliance in patients being treated for TB. Therefore, it is vitally important to have a thorough knowledge of the pathophysiology of Mtb to understand the disease progression, as well as to develop novel diagnostic tests and treatments. Alveolar macrophages represent both the primary host cell and the first line of defense against the Mtb infection. Apoptosis and autophagy of macrophages play a vital role in the pathogenesis and also in the host defense against Mtb. This review will outline the role of these two cellular processes in defense against Mtb with particular emphasis on innate immunity and explore developing therapies aimed at altering host responses to the disease.

scholarly journals Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections

2021 ◽  
Author(s):  
Paulina Niedźwiedzka-Rystwej ◽  
Dominika Bębnowska ◽  
Roman Kołacz ◽  
Wiesław Deptuła
Keyword(s):  
Pattern Recognition ◽  
Viral Infections ◽  
Apoptotic Cell ◽  
Pattern Recognition Receptors ◽  
The Body ◽  
The Other ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Other Hand

Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.

scholarly journals The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae

2017 ◽  
Vol 23 (5) ◽  
pp. 413-423 ◽  
Author(s):  
Ihsan Ullah ◽  
Neil D Ritchie ◽  
Tom J Evans
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
Neutrophil Extracellular Traps ◽  
Inhibitory Effect ◽  
Human Neutrophils ◽  
Phosphatidylinositol 3 Kinase ◽  
Cellular Processes ◽  
Extracellular Traps ◽  
Potent Inhibitory Effect

Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen.

scholarly journals Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2

2020 ◽  
Vol 93 (1112) ◽  
pp. 20200515 ◽  
Author(s):  
Tomas Franquet ◽  
Yeon Joo Jeong ◽  
Hiu Yin Sonia Lam ◽  
Ho Yuen Frank Wong ◽  
Yeun-Chung Chang ◽  
...  
Keyword(s):  
Viral Infections ◽  
Imaging Modality ◽  
Diffuse Alveolar Damage ◽  
Imaging Findings ◽  
First Line ◽  
Pictorial Review ◽  
Lung Abnormalities ◽  
Coronavirus Infection ◽  
Parenchymal Lung

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.

scholarly journals Mammalian Septins Are Required for Phagosome Formation

2008 ◽  
Vol 19 (4) ◽  
pp. 1717-1726 ◽  
Author(s):  
Yi-Wei Huang ◽  
Ming Yan ◽  
Richard F. Collins ◽  
Jessica E. DiCiccio ◽  
Sergio Grinstein ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Transient Expression ◽  
Time Course ◽  
Membrane Dynamics ◽  
Human Neutrophils ◽  
Mouse Macrophage ◽  
Macrophage Cell ◽  
Cellular Processes ◽  
Latex Beads

Septins are members of a highly conserved family of filamentous proteins that are required in many organisms for the completion of cytokinesis. In addition, septins have been implicated in a number of important cellular processes and have been suggested to have roles in regulating membrane traffic. Given the proposed role of septins in cell membrane dynamics, we investigated the function of septins during FcγR-mediated phagocytosis. We show that several septins are expressed in RAW264.7 and J774 mouse macrophage cell lines and that SEPT2 and SEPT11 are colocalized with submembranous actin-rich structures during the early stages of FcγR-mediated phagocytosis. In addition, SEPT2 accumulation is seen in primary human neutrophils and in nonprofessional phagocytes. The time course of septin accumulation mirrors actin accumulation and is inhibited by latrunculin and genistein, but not other inhibitors of phagocytosis. Inhibition of septin function by transient expression of the BD3 domain of BORG3, known to cause septin aggregation, or depletion of SEPT2 or SEPT11 by RNAi, significantly inhibited FcγR-mediated phagocytosis of IgG-coated latex beads. Interestingly, this occurred without affecting the accumulation of actin or the actin-associated protein coronin-1. These observations show that, although not necessary for actin recruitment, septins are required for efficient FcγR-mediated phagocytosis.

scholarly journals Early and Late Processes Driving NET Formation, and the Autocrine/Paracrine Role of Endogenous RAGE Ligands

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Tatsiy ◽  
Vanessa de Carvalho Oliveira ◽  
Hugo Tshivuadi Mosha ◽  
Patrick P. McDonald
Keyword(s):  
Signaling Pathways ◽  
Neutrophil Extracellular Trap ◽  
Net Generation ◽  
Human Neutrophils ◽  
Chromatin Decondensation ◽  
Cellular Processes ◽  
Activated Neutrophils ◽  
Arginine Residues ◽  
Neutrophil Response

Neutrophil extracellular trap (NET) formation has emerged as an important response against various pathogens; it also plays a role in chronic inflammation, autoimmunity, and cancer. Despite a growing understanding of the mechanisms underlying NET formation, much remains to be elucidated. We previously showed that in human neutrophils activated with different classes of physiological stimuli, NET formation features both early and late events that are controlled by discrete signaling pathways. However, the nature of these events has remained elusive. We now report that PAD4 inhibition only affects the early phase of NET generation, as do distinct signaling intermediates (TAK1, MEK, p38 MAPK). Accordingly, the inducible citrullination of residue R2 on histone H3 is an early neutrophil response that is regulated by these kinases; other arginine residues on histones H3 and H4 do not seem to be citrullinated. Conversely, elastase blockade did not affect NET formation by several physiological stimuli, though it did so in PMA-activated cells. Among belated events in NET formation, we found that chromatin decondensation is impaired by the inhibition of signaling pathways controlling both early and late stages of the phenomenon. In addition to chromatin decondensation, other late processes were uncovered. For instance, unstimulated neutrophils can condition themselves to be poised for rapid NET induction. Similarly, activated neutrophils release endogenous proteic factors that promote and largely mediate NET generation. Several such factors are known RAGE ligands and accordingly, RAGE inbibition largely prevents both NET formation and the conditioning of neutrophils to rapidly generate NETs upon stimulation. Our data shed new light on the cellular processes underlying NET formation, and unveil unsuspected facets of the phenomenon that could serve as therapeutic targets. In view of the involvement of NETs in both homeostasis and several pathologies, our findings are of broad relevance.

scholarly journals Protein synthesis regulation by leucine

2010 ◽  
Vol 46 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Daiana Vianna ◽  
Gabriela Fullin Resende Teodoro ◽  
Francisco Leonardo Torres-Leal ◽  
Julio Tirapegui
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Mrna Translation ◽  
Protein Translation ◽  
Cellular Effects ◽  
Cellular Processes ◽  
High Protein Diets

In vivo and in vitro studies have demonstrated that high protein diets affect both protein synthesis and regulation of several cellular processes. The role of amino acids as substrate for protein synthesis has been established in the literature. However, the mechanism by which these amino acids modulate transcription and regulate the mRNA translation via mTOR-dependent signaling pathway has yet to be fully determined. It has been verified that mTOR is a protein responsible for activating a cascade of biochemical intracellular events which result in the activation of the protein translation process. Of the aminoacids, leucine is the most effective in stimulating protein synthesis and reducing proteolysis. Therefore, it promotes a positive nitrogen balance, possibly by favoring the activation of this protein. This amino acid also directly and indirectly stimulates the synthesis and secretion of insulin, enhancing its anabolic cellular effects. Therefore, this review aimed to identify the role of leucine in protein synthesis modulation and to discuss the metabolic aspects related to this aminoacid.

scholarly journals Glycan–Lectin Interactions in Cancer and Viral Infections and How to Disrupt Them

2021 ◽  
Vol 22 (19) ◽  
pp. 10577
Author(s):  
Stefanie Maria Kremsreiter ◽  
Ann-Sophie Helene Kroell ◽  
Katharina Weinberger ◽  
Heike Boehm
Keyword(s):  
Immune Response ◽  
Cancer Cells ◽  
Viral Entry ◽  
Essential Role ◽  
Viral Infections ◽  
Immune Escape ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
New Therapeutic Approaches

Glycan–lectin interactions play an essential role in different cellular processes. One of their main functions is involvement in the immune response to pathogens or inflammation. However, cancer cells and viruses have adapted to avail themselves of these interactions. By displaying specific glycosylation structures, they are able to bind to lectins, thus promoting pathogenesis. While glycan–lectin interactions promote tumor progression, metastasis, and/or chemoresistance in cancer, in viral infections they are important for viral entry, release, and/or immune escape. For several years now, a growing number of investigations have been devoted to clarifying the role of glycan–lectin interactions in cancer and viral infections. Various overviews have already summarized and highlighted their findings. In this review, we consider the interactions of the lectins MGL, DC-SIGN, selectins, and galectins in both cancer and viral infections together. A possible transfer of ways to target and disrupt them might lead to new therapeutic approaches in different pathological backgrounds.

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