scholarly journals Cardiovascular Effects of Gasotransmitter Donors

2016 ◽  
pp. S291-S307 ◽  
Author(s):  
M. CEBOVÁ ◽  
M. KOŠÚTOVÁ ◽  
O. PECHÁŇOVÁ
Keyword(s):  
Carbon Monoxide ◽  
Cardiovascular Effects ◽  
Cell Types ◽  
Signaling Molecules ◽  
Cellular Effects ◽  
Hypoxic Conditions ◽  
Physiological Tasks ◽  
And Function ◽  
Different Cell Types ◽  
Anti Inflammation

Gasotransmitters represent a subfamily of the endogenous gaseous signaling molecules that include nitric oxide (NO), carbon monoxide (CO), and hydrogen sulphide (H2S). These particular gases share many common features in their production and function, but they fulfill their physiological tasks in unique ways that differ from those of classical signaling molecules found in tissues and organs. These gasotransmitters may antagonize or potentiate each other’s cellular effects at the level of their production, their downstream molecular targets and their direct interactions. All three gasotransmitters induce vasodilatation, inhibit apoptosis directly or by increasing the expression of anti-apoptotic genes, and activate antioxidants while inhibiting inflammatory actions. NO and CO may concomitantly participate in vasorelaxation, anti-inflammation and angiogenesis. NO and H2S collaborate in the regulation of vascular tone. Finally, H2S may upregulate the heme oxygenase/carbon monoxide (HO/CO) pathway during hypoxic conditions. All three gasotransmitters are produced by specific enzymes in different cell types that include cardiomyocytes, endothelial cells and smooth muscle cells. As translational research on gasotransmitters has exploded over the past years, drugs that alter the production/levels of the gasotransmitters themselves or modulate their signaling pathways are now being developed. This review is focused on the cardiovascular effects of NO, CO, and H2S. Moreover, their donors as drug targeting the cardiovascular system are briefly described.

scholarly journals cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

2019 ◽  
Vol 393 (2) ◽  
pp. 287-302 ◽  
Author(s):  
Andreas Friebe ◽  
Peter Sandner ◽  
Achim Schmidtko
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cell Types ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Therapeutic Implications ◽  
Cellular Effects ◽  
Recent Developments ◽  
And Function ◽  
Messenger Molecule

AbstractCyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC- and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the “9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications” held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

scholarly journals A systems perspective of heterocellular signaling

2018 ◽  
Vol 62 (4) ◽  
pp. 607-617 ◽  
Author(s):  
Alan Wells ◽  
H. Steven Wiley
Keyword(s):  
Cell Types ◽  
Regulatory Processes ◽  
Technical Developments ◽  
Building Models ◽  
Realistic Description ◽  
Multiple Cell ◽  
Solid Foundation ◽  
And Function ◽  
Multicellular Organisms ◽  
Different Cell Types

Signal exchange between different cell types is essential for development and function of multicellular organisms, and its dysregulation is causal in many diseases. Unfortunately, most cell-signaling work has employed single cell types grown under conditions unrelated to their native context. Recent technical developments have started to provide the tools needed to follow signaling between multiple cell types, but gaps in the information they provide have limited their usefulness in building realistic models of heterocellular signaling. Currently, only targeted assays have the necessary sensitivity, selectivity, and spatial resolution to usefully probe heterocellular signaling processes, but these are best used to test specific, mechanistic models. Decades of systems biology research with monocultures has provided a solid foundation for building models of heterocellular signaling, but current models lack a realistic description of regulated proteolysis and the feedback processes triggered within and between cells. Identification and understanding of key regulatory processes in the extracellular environment and of recursive signaling patterns between cells will be essential to building predictive models of heterocellular systems.

scholarly journals Neonatal Fc receptor (FcRn) – not only transporter of maternal IgG

2018 ◽  
Vol 72 ◽  
pp. 701-727
Author(s):  
Joanna E. Mikulska
Keyword(s):  
Mhc Class I ◽  
Current Knowledge ◽  
Cell Types ◽  
Fc Receptor ◽  
Class I ◽  
Neonatal Fc Receptor ◽  
The Status ◽  
And Function ◽  
Different Cell Types ◽  
Maternal Igg

The neonatal Fc receptor, (FcRn) is a transmembrane, heterodimeric glycoprotein with a structure similar to MHC class I molecules. In contrast to MHC class I antigens, FcRn does not bind to peptides (antigens) but interacts with the Fc fragment of IgG and albumin. The FcRn-IgG interaction as well as the FcRn-albumin interaction occur at acidic pH (optimally at pH 5.0-6.5) but not in physiological environment. These two ligands bind to distinct binding sites on the receptor molecule and by different mechanisms. Now, it is known that the expression of FcRn is not restricted to sites involved in the transport of maternal IgG, and this receptor is not responsible only for transfer the passive immunity from mother to the offspring. But FcRn has a much broader range of expression and function, throughout life and in many different cell types and tissues of humans and animals. This review summarizes the status of our knowledge on the expression, interaction with ligands and functions of the neonatal Fc receptor. This article shows also the possibilities of utilizing a current knowledge on FcRn for therapeutic purposes.

scholarly journals Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 110 ◽  
Author(s):  
Carlos de la Calle-Fabregat ◽  
Octavio Morante-Palacios ◽  
Esteban Ballestar
Keyword(s):  
Dna Methylation ◽  
Cell Types ◽  
Epigenetic Modifications ◽  
Human Organism ◽  
Cell Phenotype ◽  
Effector Cells ◽  
Technological Advances ◽  
And Function ◽  
Different Cell Types ◽  
External Stimuli

Immune cells are one of the most complex and diverse systems in the human organism. Such diversity implies an intricate network of different cell types and interactions that are dependently interconnected. The processes by which different cell types differentiate from progenitors, mature, and finally exert their function requires an orchestrated succession of molecular processes that determine cell phenotype and function. The acquisition of these phenotypes is highly dependent on the establishment of unique epigenetic profiles that confer identity and function on the various types of effector cells. These epigenetic mechanisms integrate microenvironmental cues into the genome to establish specific transcriptional programs. Epigenetic modifications bridge environment and genome regulation and play a role in human diseases by their ability to modulate physiological programs through external stimuli. DNA methylation is one of the most ubiquitous, stable, and widely studied epigenetic modifications. Recent technological advances have facilitated the generation of a vast amount of genome-wide DNA methylation data, providing profound insights into the roles of DNA methylation in health and disease. This review considers the relevance of DNA methylation to immune system cellular development and function, as well as the participation of DNA methylation defects in immune-mediated pathologies, illustrated by selected paradigmatic diseases.

scholarly journals Neural arbors are Pareto optimal

2019 ◽  
Vol 286 (1902) ◽  
pp. 20182727 ◽  
Author(s):  
Arjun Chandrasekhar ◽  
Saket Navlakha
Keyword(s):  
Network Design ◽  
Cell Body ◽  
Pareto Front ◽  
Cell Types ◽  
Brain Regions ◽  
Conduction Delay ◽  
Pareto Optimal ◽  
And Function ◽  
Graph Distances ◽  
Different Cell Types

Neural arbors (dendrites and axons) can be viewed as graphs connecting the cell body of a neuron to various pre- and post-synaptic partners. Several constraints have been proposed on the topology of these graphs, such as minimizing the amount of wire needed to construct the arbor (wiring cost), and minimizing the graph distances between the cell body and synaptic partners (conduction delay). These two objectives compete with each other—optimizing one results in poorer performance on the other. Here, we describe how well neural arbors resolve this network design trade-off using the theory of Pareto optimality. We develop an algorithm to generate arbors that near-optimally balance between these two objectives, and demonstrate that this algorithm improves over previous algorithms. We then use this algorithm to study how close neural arbors are to being Pareto optimal. Analysing 14 145 arbors across numerous brain regions, species and cell types, we find that neural arbors are much closer to being Pareto optimal than would be expected by chance and other reasonable baselines. We also investigate how the location of the arbor on the Pareto front, and the distance from the arbor to the Pareto front, can be used to classify between some arbor types (e.g. axons versus dendrites, or different cell types), highlighting a new potential connection between arbor structure and function. Finally, using this framework, we find that another biological branching structure—plant shoot architectures used to collect and distribute nutrients—are also Pareto optimal, suggesting shared principles of network design between two systems separated by millions of years of evolution.

scholarly journals Resolution of inflammation in immune and nonimmune cells by interleukin-19

2020 ◽  
Vol 319 (3) ◽  
pp. C457-C464
Author(s):  
Tani Leigh ◽  
Rosario G. Scalia ◽  
Michael V. Autieri
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Sterile Inflammation ◽  
Compensatory Mechanism ◽  
Compensatory Mechanisms ◽  
Resolution Of Inflammation ◽  
Inflammatory Stimuli ◽  
And Function ◽  
Different Cell Types

The inflammatory response is a complex, tightly regulated process activated by tissue wounding, foreign body invasion, and sterile inflammation. Over the decades, great progress has been made to advance our understanding of this process. One often overlooked aspect of inflammation is its sequel: resolution. We know that dysregulated resolution often results in numerous chronic degenerative diseases such as arthritis, cancer, and asthma. However, identification of components and mechanisms of resolving pathways lags behind those of proinflammatory processes, yet represents overlooked therapeutic opportunities. One approach is identification of endogenous, negative compensatory mechanisms, which are activated in response to inflammation for the purpose of resolution of that inflammatory stimuli. This review will focus on literature that describes expression and function of interleukin-19, a proposed anti-inflammatory cytokine, in numerous inflammatory diseases. The literature concerning IL-19 is complex, context-dependent, and often contradictory. The expression and function of IL-19 in the inflammatory response are in no way settled. We will attempt to clarify the role that this interesting and understudied cytokine plays in resolution of inflammation and discuss its mechanisms of action in different cell types. We will present a hypothesis that endogenous IL-19 expression in response to inflammatory stimuli is a cellular compensatory mechanism to dampen inflammation. We further present studies suggesting that while endogenously expressed IL-19 may be a response to inflammation, pharmacological levels may be necessary to effectively resolve the inflammatory cascade.

Spatial epigenetics: linking nuclear structure and function in higher eukaryotes

2010 ◽  
Vol 48 ◽  
pp. 25-43 ◽  
Author(s):  
Dean A. Jackson
Keyword(s):  
Nuclear Structure ◽  
Genetic Information ◽  
Nuclear Architecture ◽  
Cell Types ◽  
Structure And Function ◽  
Chromatin Dynamics ◽  
Functional Product ◽  
Higher Eukaryotes ◽  
And Function ◽  
Different Cell Types

Eukaryotic cells are defined by the genetic information that is stored in their DNA. To function, this genetic information must be decoded. In doing this, the information encoded in DNA is copied first into RNA, during RNA transcription. Primary RNA transcripts are generated within transcription factories, where they are also processed into mature mRNAs, which then pass to the cytoplasm. In the cytoplasm these mRNAs can finally be translated into protein in order to express the genetic information as a functional product. With only rare exceptions, the cells of an individual multicellular eukaryote contain identical genetic information. However, as different genes must be expressed in different cell types to define the structure and function of individual tissues, it is clear that mechanisms must have evolved to regulate gene expression. In higher eukaryotes, mechanisms that regulate the interaction of DNA with the sites where nuclear functions are performed provide one such layer of regulation. In this chapter, I evaluate how a detailed understanding of nuclear structure and chromatin dynamics are beginning to reveal how spatial mechanisms link chromatin structure and function. As these mechanisms operate to modulate the genetic information in DNA, the regulation of chromatin function by nuclear architecture defines the concept of ‘spatial epigenetics’.

scholarly journals Biophysical Support for Functionally Distinct Cell Types in the Frontal Eye Field

2009 ◽  
Vol 101 (2) ◽  
pp. 912-916 ◽  
Author(s):  
Jeremiah Y. Cohen ◽  
Pierre Pouget ◽  
Richard P. Heitz ◽  
Geoffrey F. Woodman ◽  
Jeffrey D. Schall
Keyword(s):  
Action Potentials ◽  
Cell Types ◽  
Frontal Eye Field ◽  
Subcortical Structures ◽  
Brain Areas ◽  
Visual Neurons ◽  
Distinct Cell ◽  
Eye Field ◽  
And Function ◽  
Different Cell Types

Numerous studies have described different functional cell types in the frontal eye field (FEF), but the reliability of the distinction between these types has been uncertain. Studies in other brain areas have described specific differences in the width of action potentials recorded from different cell types. To substantiate the functionally defined cell types encountered in FEF, we measured the width of spikes of visual, movement, and visuomovement types of FEF neurons in macaque monkeys. We show that visuomovement neurons had the thinnest spikes, consistent with a role in local processing. Movement neurons had the widest spikes, consistent with their role in sending eye movement commands to subcortical structures such as the superior colliculus. Visual neurons had wider spikes than visuomovement neurons, consistent with their role in receiving projections from occipital and parietal cortex. These results show how structure and function of FEF can be linked to guide inferences about neuronal architecture.

scholarly journals DEFICIENCY OF C1r IN HUMAN SERUM

1970 ◽  
Vol 131 (4) ◽  
pp. 803-815 ◽  
Author(s):  
R. J. Pickering ◽  
G. B. Naff ◽  
R. M. Stroud ◽  
R. A. Good ◽  
H. Gewurz
Keyword(s):  
Human Serum ◽  
Calcium Ions ◽  
Protein Concentration ◽  
Cell Types ◽  
Complement Activity ◽  
The Face ◽  
Hemolytic Complement Activity ◽  
And Function ◽  
Different Cell Types

The experiments presented here utilize a human serum markedly deficient in hemolytic complement activity to show that: (a) The hemolytic deficiency is the result of a selective deficiency in hemolytic C1. (b) The relative absence of hemolytic C1 is due to a profound deficit in C1r function associated with less than normal C1s protein and hemolytic function and normal C1q protein concentration and function. This deficit in C1r in the face of normal C1q suggests that different cell types are responsible for the synthesis of each of these components. (c) Whatever the basis for the deficiency of C1r function, this defect results in an inadequate association of the remaining C1 subcomponents, C1q and C1s, even in the presence of calcium ions, thus suggesting that C1r has an important role in the assembly and/or maintenance of macromolecular C1.

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