scholarly journals ROS production by localized SCHENGEN receptor module drives lignification at subcellular precision

2019 ◽  
Author(s):  
Satoshi Fujita ◽  
Damien De Bellis ◽  
Kai H. Edel ◽  
Phillipp Köster ◽  
Tonni Grube Andersen ◽  
...  
Keyword(s):  
Cell Wall ◽  
Ros Production ◽  
Spatial Control ◽  
Cellular Targets ◽  
Polar Localization ◽  
Lignin Peroxidases ◽  
Pathway Function ◽  
Underlying Mechanisms ◽  
Micrometer Scale ◽  
Precise Role

AbstractProduction of reactive-oxygen species (ROS) by NADPH oxidases (NOXs) impacts many processes in animals and plants and many plant receptor pathways involve rapid, NOX-dependent increases of ROS. Yet, their general reactivity has made it challenging to pinpoint the precise role and direct cellular targets of ROS. A well-understood ROS target in plants are lignin peroxidases in the cell wall. Lignin can be deposited with exquisite spatial control, but the underlying mechanisms have remained elusive. Here we establish a full kinase signaling relay that exerts direct, spatial control over ROS production and lignification within the cell wall. We show that polar localization of a single kinase component is crucial for pathway function. Our data indicates that an intersection of more broadly localized components allows for micrometer-scale precision of lignification and that this system is triggered through initiation of ROS production as a critical peroxidase co-substrate.

Targeting emerging Mycobacterium avium infections: perspectives into pathways and antimicrobials for future interventions

2021 ◽  
Author(s):  
Rohini Mattoo
Keyword(s):  
Drug Resistance ◽  
Cell Wall ◽  
Mycobacterium Avium ◽  
Opportunistic Pathogen ◽  
Complete Eradication ◽  
Novel Therapeutics ◽  
Unique Structure ◽  
Source Of Infection ◽  
Avium Infection ◽  
Underlying Mechanisms

Mycobacterium avium is an emerging opportunistic pathogen, globally. Infections caused by M. avium are laborious to treat and could result in drug resistance. This review discusses the importance of many factors including the cell wall in M. avium pathogenesis, since this unique structure modulates the pathogen’s ability to thrive in various hosts and environmental niches including conferring resistance to killing by antimicrobials. More research efforts in future are solicited to develop novel therapeutics targeting M. avium. The complete eradication of M. avium infection in immunocompromised individuals would need a deeper understanding of the source of infection, unique underlying mechanisms and its uncharacterized pathways. This could, perhaps in future, hold the key to target and treat M. avium more effectively.

scholarly journals From element to development: the power of the essential micronutrient boron to shape morphological processes in plants

2020 ◽  
Vol 71 (5) ◽  
pp. 1681-1693 ◽  
Author(s):  
Michaela S Matthes ◽  
Janlo M Robil ◽  
Paula McSteen
Keyword(s):  
Cell Wall ◽  
Current Understanding ◽  
Micronutrient Deficiencies ◽  
Developmental Defects ◽  
Essential Nutrient ◽  
Experimental Approaches ◽  
Morphological Processes ◽  
Underlying Mechanisms ◽  
Mutant Phenotypes

Abstract Deficiency of the essential nutrient boron (B) in the soil is one of the most widespread micronutrient deficiencies worldwide, leading to developmental defects in root and shoot tissues of plants, and severe yield reductions in many crops. Despite this agricultural importance, the underlying mechanisms of how B shapes plant developmental and morphological processes are still not unequivocally understood in detail. This review evaluates experimental approaches that address our current understanding of how B influences plant morphological processes by focusing on developmental defects observed under B deficiency. We assess what is known about mechanisms that control B homeostasis and specifically highlight: (i) limitations in the methodology that is used to induce B deficiency; (ii) differences between mutant phenotypes and normal plants grown under B deficiency; and (iii) recent research on analyzing interactions between B and phytohormones. Our analysis highlights the need for standardized methodology to evaluate the roles of B in the cell wall versus other parts of the cell.

scholarly journals Combination Treatment with Cold Physical Plasma and Pulsed Electric Fields Augments ROS Production and Cytotoxicity in Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 845 ◽  
Author(s):  
Christina M. Wolff ◽  
Juergen F. Kolb ◽  
Klaus-Dieter Weltmann ◽  
Thomas von Woedtke ◽  
Sander Bekeschus
Keyword(s):  
Electric Fields ◽  
Combination Treatment ◽  
Argon Plasma ◽  
Pulsed Electric Fields ◽  
Drug Uptake ◽  
Minor Role ◽  
Ros Production ◽  
Treatment Regimens ◽  
Underlying Mechanisms ◽  
Physical Plasma

New approaches in oncotherapy rely on the combination of different treatments to enhance the efficacy of established monotherapies. Pulsed electric fields (PEFs) are an established method (electrochemotherapy) for enhancing cellular drug uptake while cold physical plasma is an emerging and promising anticancer technology. This study aimed to combine both technologies to elucidate their cytotoxic potential as well as the underlying mechanisms of the effects observed. An electric field generator (0.9–1.0 kV/cm and 100-μs pulse duration) and an atmospheric pressure argon plasma jet were employed for the treatment of lymphoma cell lines as a model system. PEF but not plasma treatment induced cell membrane permeabilization. Additive cytotoxicity was observed for the metabolic activity and viability of the cells while the sequence of treatment in the combination played only a minor role. Intriguingly, a parallel combination was more effective compared to a 15-min pause between both treatment regimens. A combination effect was also found for lipid peroxidation; however, none could be observed in the cytosolic and mitochondrial reactive oxygen species (ROS) production. The supplementation with either antioxidant, a pan-caspase-inhibitor or a ferroptosis inhibitor, all partially rescued lymphoma cells from terminal cell death, which contributes to the mechanistic understanding of this combination treatment.

scholarly journals Regulation of sugar metabolism genes in the nitrogen-dependent susceptibility of tomato stems to Botrytis cinerea

2020 ◽  
Vol 127 (1) ◽  
pp. 143-154
Author(s):  
Nathalie Lacrampe ◽  
Félicie Lopez-Lauri ◽  
Raphaël Lugan ◽  
Sophie Colombié ◽  
Jérôme Olivares ◽  
...  
Keyword(s):  
Cell Wall ◽  
Botrytis Cinerea ◽  
Sucrose Synthase ◽  
Nitrogen Availability ◽  
Soluble Sugars ◽  
Plant Defence ◽  
Sugar Metabolism ◽  
Sugar Transporters ◽  
Expression Of Genes ◽  
Underlying Mechanisms

Abstract Background and Aims The main soluble sugars are important components of plant defence against pathogens, but the underlying mechanisms are unclear. Upon infection by Botrytis cinerea, the activation of several sugar transporters, from both plant and fungus, illustrates the struggle for carbon resources. In sink tissues, the metabolic use of the sugars mobilized in the synthesis of defence compounds or antifungal barriers is not fully understood. Methods In this study, the nitrogen-dependent variation of tomato stem susceptibility to B. cinerea was used to examine, before and throughout the course of infection, the transcriptional activity of enzymes involved in sugar metabolism. Under different nitrate nutrition regimes, the expression of genes that encode the enzymes of sugar metabolism (invertases, sucrose synthases, hexokinases, fructokinases and phosphofructokinases) was determined and sugar contents were measured before inoculation and in asymptomatic tissues surrounding the lesions after inoculation. Key Results At high nitrogen availability, decreased susceptibility was associated with the overexpression of several genes 2 d after inoculation: sucrose synthases Sl-SUS1 and Sl-SUS3, cell wall invertases Sl-LIN5 to Sl-LIN9 and some fructokinase and phosphofructokinase genes. By contrast, increased susceptibility corresponded to the early repression of several genes that encode cell wall invertase and sucrose synthase. The course of sugar contents was coherent with gene expression. Conclusions The activation of specific genes that encode sucrose synthase is required for enhanced defence. Since the overexpression of fructokinase is also associated with reduced susceptibility, it can be hypothesized that supplementary sucrose cleavage by sucrose synthases is dedicated to the production of cell wall components from UDP-glucose, or to the additional implication of fructose in the synthesis of antimicrobial compounds, or both.

scholarly journals Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey

2021 ◽  
Vol 8 ◽  
Author(s):  
Donato Cappetta ◽  
Antonella De Angelis ◽  
Gabriella Bellocchio ◽  
Marialucia Telesca ◽  
Eleonora Cianflone ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ion Homeostasis ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Cellular Targets ◽  
Multifactorial Diseases ◽  
Positive Effects ◽  
Sodium Glucose Cotransporter ◽  
Underlying Mechanisms ◽  
The Moment

Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. The restoration of cardiac Na+ levels with consequent positive effects on Ca2+ handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs.

scholarly journals Synthesis and Biological Aspects of Mycolic Acids: An Important Target AgainstMycobacterium tuberculosis

2008 ◽  
Vol 8 ◽  
pp. 720-751 ◽  
Author(s):  
Marcus Vinícius Nora de Souza ◽  
Marcelle de Lima Ferreira ◽  
Alessandra Campbell Pinheiro ◽  
Maurício Frota Saraiva ◽  
Mauro Vieira de Almeida ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Cell Walls ◽  
Important Class ◽  
Cellular Targets ◽  
Mycolic Acids ◽  
Important Target ◽  
Novel Drugs ◽  
Biological Aspects ◽  
Mycobacterial Cell Wall

Mycolic acids are an important class of compounds, basically found in the cell walls of a group of bacteria known as mycolata taxon, exemplified by the most famous bacteria of this group, theMycobacterium tuberculosis(M. tb.), the agent responsible for the disease known as tuberculosis (TB). Mycolic acids are important for the survival of M. tb. For example, they are able to help fight against hydrophobic drugs and dehydration, and also allow this bacterium to be more effective in the host's immune system by growing inside macrophages. Due to the importance of the mycolic acids for maintenance of the integrity of the mycobacterial cell wall, these compounds become attractive cellular targets for the development of novel drugs against TB. In this context, the aim of this article is to highlight the importance of mycolic acids in drug discovery.

scholarly journals Unique lignin modifications pattern the nucleation of silica in sorghum endodermis

2020 ◽  
Vol 71 (21) ◽  
pp. 6818-6829 ◽  
Author(s):  
Nerya Zexer ◽  
Rivka Elbaum
Keyword(s):  
Cell Wall ◽  
Silicic Acid ◽  
Cell Walls ◽  
Dry Weight ◽  
Cell Wall Chemistry ◽  
Modified Lignin ◽  
Trace Concentrations ◽  
High Degree ◽  
Micrometer Scale ◽  
The Impact

Abstract Silicon dioxide in the form of hydrated silica is a component of plant tissues that can constitute several percent by dry weight in certain taxa. Nonetheless, the mechanism of plant silica formation is mostly unknown. Silicon (Si) is taken up from the soil by roots in the form of monosilicic acid molecules. The silicic acid is carried in the xylem and subsequently polymerizes in target sites to silica. In roots of sorghum (Sorghum bicolor), silica aggregates form in an orderly pattern along the inner tangential cell walls of endodermis cells. Using Raman microspectroscopy, autofluorescence, and scanning electron microscopy, we investigated the structure and composition of developing aggregates in roots of sorghum seedlings. Putative silica aggregation loci were identified in roots grown under Si starvation. These micrometer-scale spots were constructed of tightly packed modified lignin, and nucleated trace concentrations of silicic acid. Substantial variation in cell wall autofluorescence between Si+ and Si– roots demonstrated the impact of Si on cell wall chemistry. We propose that in Si– roots, the modified lignin cross-linked into the cell wall and lost its ability to nucleate silica. In Si+ roots, silica polymerized on the modified lignin and altered its structure. Our work demonstrates a high degree of control over lignin and silica deposition in cell walls.

scholarly journals Epithelial delamination is protective during pharmaceutical-induced enteropathy

2019 ◽  
Vol 116 (34) ◽  
pp. 16961-16970 ◽  
Author(s):  
Scott T. Espenschied ◽  
Mark R. Cronan ◽  
Molly A. Matty ◽  
Olaf Mueller ◽  
Matthew R. Redinbo ◽  
...  
Keyword(s):  
Efflux Pumps ◽  
Antiinflammatory Drug ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Microbial Colonization ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Cellular Targets ◽  
Unfolded Protein ◽  
Underlying Mechanisms ◽  
The Unfolded Protein Response

Intestinal epithelial cell (IEC) shedding is a fundamental response to intestinal damage, yet underlying mechanisms and functions have been difficult to define. Here we model chronic intestinal damage in zebrafish larvae using the nonsteroidal antiinflammatory drug (NSAID) Glafenine. Glafenine induced the unfolded protein response (UPR) and inflammatory pathways in IECs, leading to delamination. Glafenine-induced inflammation was augmented by microbial colonization and associated with changes in intestinal and environmental microbiotas. IEC shedding was a UPR-dependent protective response to Glafenine that restricts inflammation and promotes animal survival. Other NSAIDs did not induce IEC delamination; however, Glafenine also displays off-target inhibition of multidrug resistance (MDR) efflux pumps. We found a subset of MDR inhibitors also induced IEC delamination, implicating MDR efflux pumps as cellular targets underlying Glafenine-induced enteropathy. These results implicate IEC delamination as a protective UPR-mediated response to chemical injury, and uncover an essential role for MDR efflux pumps in intestinal homeostasis.

scholarly journals Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jane Macnaughtan ◽  
Rajeshwar P. Mookerjee ◽  
Schalk van der Merwe ◽  
Rajiv Jalan
Keyword(s):  
Venous Blood ◽  
Alcoholic Cirrhosis ◽  
Neutrophil Function ◽  
Ros Production ◽  
Variceal Haemorrhage ◽  
Functional Defect ◽  
Organ Failures ◽  
Portal Venous Blood ◽  
Reactive Oxidant ◽  
Underlying Mechanisms

Abstract Systemic lipopolysaccharide (LPS) is implicated in increasing mortality in patients with alcoholic hepatitis but the underlying mechanisms are not well characterised. The objective of this study was to characterise neutrophil function, LPS and cytokine concentrations within the splanchnic circulation of alcoholic cirrhotic patients undergoing TIPSS insertion for variceal haemorrhage and correlate this with outcome. 26 patients with alcoholic cirrhosis and variceal haemorrhage were studied prior to and 1-hour after TIPSS insertion. Neutrophil function, LPS and cytokine concentrations were determined in arterial, hepatic venous (HV) and portal venous blood (PV). Significantly higher LPS concentrations and neutrophil reactive oxidant species (ROS) production were observed in PV vs HV blood. Cross-incubation of HV plasma with PV neutrophils resulted in reduced ROS production. Insertion of TIPSS was associated with a significant increase in arterial LPS concentrations and deterioration in neutrophil phagocytosis. Number of organ failures and arterial IL-6 concentrations at presentation were associated with increased mortality. The portal circulation has a distinct immunological milieu characterised by a pathological neutrophil phenotype and an anti-inflammatory cytokine profile associated with heightened LPS levels. TIPSS insertion renders this neutrophil functional defect systemic, associated with an increase in arterial LPS and a susceptibility to sepsis.

scholarly journals Exendin-4 protects endothelial cells from lipoapoptosis by PKA, PI3K, eNOS, p38 MAPK, and JNK pathways

2013 ◽  
Vol 50 (2) ◽  
pp. 229-241 ◽  
Author(s):  
Özlem Erdogdu ◽  
Linnéa Eriksson ◽  
Hua Xu ◽  
Åke Sjöholm ◽  
Qimin Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Experimental Studies ◽  
Receptor Activation ◽  
No Production ◽  
Ros Production ◽  
Human Coronary Artery ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Experimental studies have indicated that endothelial cells play an important role in maintaining vascular homeostasis. We previously reported that human coronary artery endothelial cells (HCAECs) express the glucagon-like peptide 1 (GLP1) receptor and that the stable GLP1 mimetic exendin-4 is able to activate the receptor, leading to increased cell proliferation. Here, we have studied the effect of exendin-4 and native GLP1 (7–36) on lipoapoptosis and its underlying mechanisms in HCAECs. Apoptosis was assessed by DNA fragmentation and caspase-3 activation, after incubating cells with palmitate. Nitric oxide (NO) and reactive oxidative species (ROS) were analyzed. GLP1 receptor activation, PKA-, PI3K/Akt-, eNOS-, p38 MAPK-, and JNK-dependent pathways, and genetic silencing of transfection of eNOS were also studied. Palmitate-induced apoptosis stimulated cells to release NO and ROS, concomitant with upregulation of eNOS, which required activation of p38 MAPK and JNK. Exendin-4 restored the imbalance between NO and ROS production in which ROS production decreased and NO production was further augmented. Incubation with exendin-4 and GLP1 (7–36) protected HCAECs against lipoapoptosis, an effect that was blocked by PKA, PI3K/Akt, eNOS, p38 MAPK, and JNK inhibitors. Genetic silencing of eNOS also abolished the anti-apoptotic effect afforded by exendin-4. Our results support the notion that GLP1 receptor agonists restore eNOS-induced ROS production due to lipotoxicity and that such agonists protect against lipoapoptosis through PKA-PI3K/Akt-eNOS-p38 MAPK-JNK-dependent pathways via a GLP1 receptor-dependent mechanism.

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