scholarly journals Platelet-activating factor: receptors and signal transduction

1993 ◽  
Vol 292 (3) ◽  
pp. 617-629 ◽  
Author(s):  
W Chao ◽  
M S Olson
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Molecular Genetic ◽  
Platelet Activating Factor ◽  
Cellular Adhesion ◽  
Cellular Adhesion Molecules ◽  
The Past ◽  
Signalling Molecule ◽  
Paf Receptor

During the past two decades, studies describing the chemistry and biology of PAF have been extensive. This potent phosphoacylglycerol exhibits a wide variety of physiological and pathophysiological effects in various cells and tissues. PAF acts, through specific receptors and a variety of signal transduction systems, to elicit diverse biochemical responses. Several important future directions can be enumerated for the characterization of PAF receptors and their attendant signalling mechanisms. The recent cloning and sequence analysis of the gene for the PAF receptor will allow a number of important experimental approaches for characterizing the structure and analysing the function of the various domains of the receptor. Using molecular genetic and immunological technologies, questions relating to whether there is receptor heterogeneity, the precise mechanism(s) for the regulation of the PAF receptor, and the molecular details of the signalling mechanisms in which the PAF receptor is involved can be explored. Another area of major significance is the examination of the relationship between the signalling response(s) evoked by PAF binding to its receptor and signalling mechanisms activated by a myriad of other mediators, cytokines and growth factors. A very exciting recent development in which PAF receptors undoubtedly play a role is in the regulation of the function of various cellular adhesion molecules. Finally, there remain many incompletely characterized physiological and pathophysiological situations in which PAF and its receptor play a crucial signalling role. Our laboratory has been active in the elucidation of several tissue responses in which PAF exhibits major autocoid signalling responses, e.g. hepatic injury and inflammation, acute and chronic pancreatitis, and cerebral stimulation and/or trauma. As new experimental strategies are developed for characterizing the fine structure of the molecular mechanisms involved in tissue injury and inflammation, the essential role of PAF as a primary signalling molecule will be affirmed. Doubtless the next 20 years of experimental activity will be even more interesting and productive than the past two decades.

Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells

1997 ◽  
Vol 273 (2) ◽  
pp. G342-G347
Author(s):  
H. Ichikawa ◽  
R. E. Wolf ◽  
T. Y. Aw ◽  
N. Ohno ◽  
L. Coe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Injury ◽  
Umbilical Vein ◽  
Platelet Activating Factor ◽  
Adhesion Assay ◽  
Neutrophil Adherence ◽  
Paf Receptor ◽  
Umbilical Vein Endothelial Cells ◽  
Adhesive Effect ◽  
Paf Receptor Antagonist

Oxidants generated by endothelial xanthine oxidase (XO) can help trigger free radical-mediated tissue injury. An important event in oxidant-mediated tissue injury is neutrophil-endothelial adhesion. Although activation of endothelial XO increases adhesion, little is known about xanthine in the adhesive effect of XO. This study examined administered xanthine on the adhesion of neutrophils. Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were exposed to xanthine (15 min), and neutrophils were allowed to adhere to HUVEC in an adhesion assay. Adhesion was dose dependently increased by xanthine (3-100 microM). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 microM), or platelet-activating factor (PAF) receptor antagonist (WEB 2086; 10 microM) reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect. Pretreatment of HUVEC with 50 microM tungsten also blocked xanthine-induced adherence. Adhesion was also inhibited by preincubation with 100 U/ml heparin. Finally, anti-P-selectin antibody (PB1.3; 20 micrograms/ml) attenuated adhesion. Our results indicate that xanthine may promote neutrophil-endothelial adhesion via a hydrogen peroxide- and PAF-mediated P-selectin expression.

scholarly journals Genes involved in brassinosteroids's metabolism and signal transduction pathways

2007 ◽  
Vol 50 (4) ◽  
pp. 605-618 ◽  
Author(s):  
Adaucto Bellarmino Pereira-Netto
Keyword(s):  
Signal Transduction ◽  
Biosynthetic Pathway ◽  
Molecular Mechanisms ◽  
Signal Transduction Pathway ◽  
Normal Growth ◽  
The Past ◽  
C 23 ◽  
Pathway Regulation ◽  
Regulation Of Cell Cycle

Brassinosteroids (BRs) are plant steroids essential for the normal growth and development, which carry an oxygen moiety at C-3 and additional ones at one or more of the C-2, C-6, C-22 and C-23 carbon atoms. In the past few years, application of molecular genetics allowed significant progress on the understanding of the BRs biosynthetic pathway regulation and on the identification of several components of their signal transduction pathway, as well. Search in eletronic databases show dozens of records for brassinosteroid-related genes for the last twelve months, demonstrating the big efforts being carried out in this field. This review highlights the recent advances on the characterization of genes and mutations that are helping to unravel the molecular mechanisms involved in the BRs synthesis/metabolism, perception and response, with especial emphasis on their role in plant cell elongation. Aspects of the involvement of BRs on the regulation of cell cycle-controlling proteins are discussed as well.

Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo

1994 ◽  
Vol 266 (2) ◽  
pp. H637-H642 ◽  
Author(s):  
J. P. Gaboury ◽  
D. C. Anderson ◽  
P. Kubes
Keyword(s):  
Molecular Mechanisms ◽  
Leukocyte Adhesion ◽  
Platelet Activating Factor ◽  
Leukocyte Rolling ◽  
Rolling Velocity ◽  
Paf Receptor ◽  
Rolling Leukocytes ◽  
Adherent Leukocytes ◽  
Web 2086

Intravital microscopy was used to monitor leukocyte adherence, flux, rolling velocity, and number of rolling leukocytes (flux/velocity) in venules 25–40 microns in diameter. The superoxide-generating system, hypoxanthine and xanthine oxidase (HX/XO), was infused into the mesenteric circulation in untreated animals or in animals pretreated with either catalase (a hydrogen peroxide scavenger), WEB-2086 [a platelet-activating factor (PAF) receptor antagonist], or monoclonal antibodies directed against adhesion molecules CD18 (CL26) or P-selectin (PB1.3). HX/XO infusion caused a decrease in leukocyte rolling velocity and an increase in the number of rolling and adherent leukocytes. WEB-2086 prevented the increase in leukocyte adhesion and markedly increased leukocyte rolling velocity. PB1.3 abolished the HX/XO-associated rise in the flux of rolling leukocytes and proportionally decreased the number of adherent leukocytes. CL26 abolished HX/XO-induced leukocyte adhesion and also reduced the number of rolling leukocytes. In conclusion, P-selectin mediates the increased leukocyte flux induced by superoxide, whereas PAF and CD18 modulate leukocyte adhesion. PAF also reduces leukocyte rolling velocity, possibly as a result of CD18, but not P-selectin.

Auxin signal transduction

2015 ◽  
Vol 58 ◽  
pp. 1-12 ◽  
Author(s):  
Gretchen Hagen
Keyword(s):  
Signal Transduction ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Auxin Receptor ◽  
Future Goals ◽  
Repressor Proteins ◽  
Auxin Binding ◽  
Transcriptional Complex ◽  
Auxin Signal Transduction

The plant hormone auxin (indole-3-acetic acid, IAA) controls growth and developmental responses throughout the life of a plant. A combination of molecular, genetic and biochemical approaches has identified several key components involved in auxin signal transduction. Rapid auxin responses in the nucleus include transcriptional activation of auxin-regulated genes and degradation of transcriptional repressor proteins. The nuclear auxin receptor is an integral component of the protein degradation machinery. Although auxin signalling in the nucleus appears to be short and simple, recent studies indicate that there is a high degree of diversity and complexity, largely due to the existence of multigene families for each of the major molecular components. Current studies are attempting to identify interacting partners among these families, and to define the molecular mechanisms involved in the interactions. Future goals are to determine the levels of regulation of the key components of the transcriptional complex, to identify higher-order complexes and to integrate this pathway with other auxin signal transduction pathways, such as the pathway that is activated by auxin binding to a different receptor at the outer surface of the plasma membrane. In this case, auxin binding triggers a signal cascade that affects a number of rapid cytoplasmic responses. Details of this pathway are currently under investigation.

Modeling of molecular mechanisms of cell adhesion

1995 ◽  
Vol 73 (7-8) ◽  
pp. 399-409 ◽  
Author(s):  
B. A. Skierczynski ◽  
R. Skalak ◽  
S. Chien
Keyword(s):  
Signal Transduction ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Cellular Adhesion ◽  
Receptor Interaction ◽  
Interaction Modeling ◽  
Molecular Interpretation ◽  
Adhesion Ligand ◽  
Adhesion Process

Cellular adhesion is a process of great importance in biology. We present a simple model of the adhesion process in which the molecular mechanisms involve a receptor, a ligand, and the cytoskeleton of the cell. Based on the energetic consideration of the process, we propose a molecular interpretation of the existing experimental data. The model suggests that the interaction of the receptor and (or) receptor-ligand with the cytoskeleton can have important influence on the formation and strength of the adhesion complex as well as on the subsequent interaction with different ligands. When conformational changes take place during the adhesion process, the characterization of the adhesion bonds based on chemical kinetics alone seems to be incomplete and must be supplemented by parameters, describing the functionality of the complex, i.e., change of the affinity for different ligands, as in the signal transduction, or the strength of the bond, as in the adhesion process.Key words: adhesion, ligand–receptor interaction, modeling, signal transduction, conformational changes.

Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma

1992 ◽  
Vol 263 (4) ◽  
pp. R909-R914
Author(s):  
A. I. Faden ◽  
P. A. Tzendzalian
Keyword(s):  
Tissue Damage ◽  
Tissue Injury ◽  
Platelet Activating Factor ◽  
Neuronal Cell ◽  
Receptor Antagonists ◽  
Tissue Water ◽  
Behavioral Deficits ◽  
Phospholipid Hydrolysis ◽  
Neuronal Cell Lines ◽  
Paf Receptor

Tissue damage after traumatic brain injury (TBI) results in part from delayed biochemical changes initiated by the insult. Platelet-activating factor (PAF) is an alkylphospholipid that has been implicated in tissue damage after cerebral ischemia. PAF is toxic to certain neuronal cell lines in culture, reduces cerebral blood flow, alters the blood-brain barrier, and can enhance phospholipid hydrolysis. The recent development of receptor antagonists to PAF permits examination of its possible role in delayed tissue injury after neurotrauma. Treatment with the PAF receptor antagonists BN 52021 and WEB 2170 before injury significantly enhanced neurological recovery after fluid percussion-induced TBI in rats. Pretreatment with WEB 2170 also significantly limited alterations in tissue water content and tissue glycine levels after trauma, and reduced posttraumatic levels of extracellular glycine in ipsilateral hippocampus. These findings implicate PAF in the pathophysiology of TBI, through actions at PAF receptors. A possible role for glycine in this process is suggested.

scholarly journals Dysfunctional epileptic neuronal circuits and dysmorphic dendritic spines are mitigated by platelet-activating factor receptor antagonism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Alberto E. Musto ◽  
Robert F. Rosencrans ◽  
Chelsey P. Walker ◽  
Surjyadipta Bhattacharjee ◽  
Chittalsinh M. Raulji ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Molecular Mechanisms ◽  
Dorsal Hippocampus ◽  
Platelet Activating Factor ◽  
Rodent Models ◽  
Spine Density ◽  
Interictal Spikes ◽  
Dendritic Spine Density ◽  
Paf Receptor

Abstract Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15–16 weeks after LE using multi-array silicon probe electrodes implanted in the dorsal hippocampus, are reduced in PAF-r antagonist-treated mice. We suggest that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy.

scholarly journals Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury

2020 ◽  
Vol 6 (12) ◽  
pp. eaay6314 ◽  
Author(s):  
Jörn Karhausen ◽  
Hae Woong Choi ◽  
Krishna Rao Maddipati ◽  
Joseph P. Mathew ◽  
Qing Ma ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Platelet Activation ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Platelet Activating Factor ◽  
Organ Injury ◽  
Paf Receptor ◽  
Platelet Aggregates ◽  
Systemic Responses

Platelet responses have been associated with end-organ injury and mortality following complex insults such as cardiac surgery, but how platelets contribute to these pathologies remains unclear. Our studies originated from the observation of microvascular platelet retention in a rat cardiac surgery model. Ensuing work supported the proximity of platelet aggregates with perivascular mast cells (MCs) and demonstrated that platelet activation triggered systemic MC activation. We then identified platelet activating factor (PAF) as the platelet-derived mediator stimulating MCs and, using chimeric animals with platelets defective in PAF generation or MCs lacking PAF receptor, defined the role of this platelet-MC interaction for vascular leakage, shock, and tissue inflammation. In application of these findings, we demonstrated that inhibition of platelet activation in modeled cardiac surgery blunted MC-dependent inflammation and tissue injury. Together, our work identifies a previously undefined mechanism of inflammatory augmentation, in which platelets trigger local and systemic responses through activation of perivascular MCs.

Segregation of cell adhesion molecules into membrane microdomains facilitates leukocyte-endothelial interactions

1995 ◽  
Vol 53 ◽  
pp. 780-781
Author(s):  
S.L. Erlandsen
Keyword(s):  
Cell Surface ◽  
Adhesion Molecules ◽  
Colloidal Gold ◽  
High Spatial Resolution ◽  
Low Voltage ◽  
Cellular Adhesion ◽  
Membrane Microdomains ◽  
Immunogold Label ◽  
Cellular Adhesion Molecules ◽  
Electron Detection

Cells interact with their extracellular environments by means of a variety of cellular adhesion molecules (CAM) and surface ligands. In many instances, CAMs interact in a sequential temporal fashion which suggests that these adhesion molecules may occupy or be polarized to various membrane microdomains on the cell surface. Detection of CAMs can be accomplished by a variety of methods including immunofluorescent microscopy and flow cytometry, and by the use of immunocytochemical markers (i.e. colloidal gold) in electron microscopy. The development of high resolution field emission SEM in the mid 1980's and the Autrata modification of the YAG detector for backscatter electron detection at low voltage has greatly facilitated the recognition of colloidal gold probes for detection of surface CAMs. Low voltage FESEM with Bse imaging provides increased resolution of cell surface topography (~3nm at 3-4 keV) which can be observed in 3-dimensions, and simultaneously permits detection/high spatial resolution of immunogold label by atomic number contrast.

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