scholarly journals Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CCl4-Treated Fibrotic Mice

2020 ◽  
Vol 21 (7) ◽  
pp. 2305 ◽  
Author(s):  
Erandi Velázquez-Miranda ◽  
Christian Molina-Aguilar ◽  
Adriana González-Gallardo ◽  
Olivia Vázquez-Martínez ◽  
Mauricio Díaz-Muñoz ◽  
...  
Keyword(s):  
Purinergic Signaling ◽  
P2y Receptors ◽  
Transcriptional Analysis ◽  
Zonal Distribution ◽  
P2y2 Receptors ◽  
Action Mechanisms ◽  
Ccl4 Administration ◽  
Enhanced Expression ◽  
And Function

Inflammatory and wound healing responses take place during liver damage, primarily in the parenchymal tissue. It is known that cellular injury elicits an activation of the purinergic signaling, mainly by the P2X7 receptor; however, the role of P2Y receptors in the onset of liver pathology such as fibrosis has not been explored. Hence, we used mice treated with the hepatotoxin CCl4 to implement a reversible model of liver fibrosis to evaluate the expression and function of the P2Y2 receptor (P2Y2R). Fibrotic livers showed an enhanced expression of P2Y2R that eliminated its zonal distribution. Hepatocytes from CCl4-treated mice showed an exacerbated ERK-phosphorylated response to the P2Y2R-specific agonist, UTP. Cell proliferation was also enhanced in the fibrotic livers. Hepatic transcriptional analysis by microarrays, upon CCl4 administration, showed that P2Y2 activation regulated diverse pathways, revealing complex action mechanisms. In conclusion, our data indicate that P2Y2R activation is involved in the onset of the fibrotic damage associated with the reversible phase of the hepatic damage promoted by CCl4.

scholarly journals Histone H2B as a functionally important plasminogen receptor on macrophages

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3763-3772 ◽  
Author(s):  
Riku Das ◽  
Tim Burke ◽  
Edward F. Plow
Keyword(s):  
Binding Capacity ◽  
Peritoneal Macrophages ◽  
Blood Monocytes ◽  
Histone H2b ◽  
Cell Recruitment ◽  
Annexin 2 ◽  
Enhanced Expression ◽  
And Function ◽  
Mouse Peritoneal Macrophages

AbstractPlasminogen (Plg) facilitates inflammatory cell recruitment, a function that depends upon its binding to Plg receptors (Plg-Rs). However, the Plg-Rs that are critical for cell migration are not well defined. Three previously characterized Plg-Rs (α-enolase, annexin 2, and p11) and a recently identified Plg-R (histone H2B [H2B]) were assessed for their contribution to Plg binding and function on macrophages. Two murine macrophage cell lines (RAW 264.7 and J774A.1) and mouse peritoneal macrophages induced by thioglycollate were analyzed. All 4 Plg-Rs were present on the surface of these cells and showed enhanced expression on the thioglycollate-induced macrophages compared with peripheral blood monocytes. Using blocking Fab fragments to each Plg-R, H2B supported approximately 50% of the Plg binding capacity, whereas the other Plg-Rs contributed less than 25%. Anti-H2B Fab also demonstrated a major role of this Plg-R in plasmin generation and matrix invasion. When mice were treated intravenously with anti-H2B Fab, peritoneal macrophage recruitment in response to thioglycollate was reduced by approximately 45% at 24, 48, and 72 hours, with no effect on blood monocyte levels. Taken together, these data suggest that multiple Plg-Rs do contribute to Plg binding to macrophages, and among these, H2B plays a very prominent and functionally important role.

scholarly journals The Impact of Purinergic System Enzymes on Noncommunicable, Neurological, and Degenerative Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-21 ◽  
Author(s):  
Margarete Dulce Bagatini ◽  
Alessandra Antunes dos Santos ◽  
Andréia Machado Cardoso ◽  
Aline Mânica ◽  
Cristina Ruedell Reschke ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Purinergic Signaling ◽  
P2y Receptors ◽  
Degenerative Diseases ◽  
Limited Effectiveness ◽  
Central Nervous Systems ◽  
Health And Disease ◽  
The Impact

Evidences show that purinergic signaling is involved in processes associated with health and disease, including noncommunicable, neurological, and degenerative diseases. These diseases strike from children to elderly and are generally characterized by progressive deterioration of cells, eventually leading to tissue or organ degeneration. These pathological conditions can be associated with disturbance in the signaling mediated by nucleotides and nucleosides of adenine, in expression or activity of extracellular ectonucleotidases and in activation of P2X and P2Y receptors. Among the best known of these diseases are atherosclerosis, hypertension, cancer, epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). The currently available treatments present limited effectiveness and are mostly palliative. This review aims to present the role of purinergic signaling highlighting the ectonucleotidases E-NTPDase, E-NPP, E-5′-nucleotidase, and adenosine deaminase in noncommunicable, neurological, and degenerative diseases associated with the cardiovascular and central nervous systems and cancer. In conclusion, changes in the activity of ectonucleotidases were verified in all reviewed diseases. Although the role of ectonucleotidases still remains to be further investigated, evidences reviewed here can contribute to a better understanding of the molecular mechanisms of highly complex diseases, which majorly impact on patients’ quality of life.

scholarly journals Expression and function of rat urothelial P2Y receptors

2008 ◽  
Vol 294 (4) ◽  
pp. F821-F829 ◽  
Author(s):  
Bikramjit Chopra ◽  
Joel Gever ◽  
Stacey R. Barrick ◽  
Ann T. Hanna-Mitchell ◽  
Jonathan M. Beckel ◽  
...  
Keyword(s):  
Purinergic Signaling ◽  
Rank Order ◽  
Atp Release ◽  
P2y Receptors ◽  
Urothelial Cells ◽  
Paracrine Signaling ◽  
Rat Urinary Bladder ◽  
Afferent Fibers ◽  
And Function ◽  
Lower Urinary

The control and regulation of the lower urinary tract are partly mediated by purinergic signaling. This study investigated the distribution and function of P2Y receptors in the rat urinary bladder. Application of P2Y agonists to rat urothelial cells evoked increases in intracellular calcium; the rank order of agonist potency (pEC50 ± SE) was ATP (5.10 ± 0.07) > UTP (4.91 ± 0.14) > UTPγS (4.61 ± 0.16) = ATPγS (4.70 ± 0.05) > 2-methylthio adenosine 5′-diphosphate = 5′-( N-ethylcarboxamido)adenosine = ADP (<3.5). The rank order potency for these agonists indicates that urothelial cells functionally express P2Y2/P2Y4 receptors, with a relative lack of contribution from other P2Y or adenosine receptors. Real-time PCR, Western blotting, and immunocytochemistry confirmed the expression of P2Y2 and to a lesser extent P2Y4 in the urothelium. Immunocytochemical studies revealed expression of P2Y2 staining in all layers of the urothelium, with relative absence of P2Y4. P2Y2 staining was also present in suburothelial nerve bundles and underlying detrusor smooth muscle. Addition of UTP and UTPγS was found to evoke ATP release from cultured rat urothelial cells. These findings indicate that cultured rat urothelial cells functionally express P2Y2/P2Y4 receptors. Activation of these receptors could have a role in autocrine and paracrine signaling throughout the urothelium. This could lead to the release of bioactive mediators such as additional ATP, nitric oxide, and acetylcholine, which can modulate the micturition reflex by acting on suburothelial myofibroblasts and/or pelvic afferent fibers.

scholarly journals β-arrestin-1 participates in thrombosis and regulates integrin αIIbβ3 signalling without affecting P2Y receptors desensitisation and function

2012 ◽  
Vol 107 (04) ◽  
pp. 735-748 ◽  
Author(s):  
Mathieu Schaff ◽  
Nicolas Receveur ◽  
Catherine Bourdon ◽  
Philippe Ohlmann ◽  
François Lanza ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thrombus Formation ◽  
P2y Receptors ◽  
Integrin Αiibβ3 ◽  
Akt Phosphorylation ◽  
Fibrinogen Binding ◽  
And Function ◽  
G Protein Coupled ◽  
Receptor Desensitisation

Summaryβ-arrestin-1 (β-arr1) and β-arrestin-2 (β-arr2) are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling. We used genetically-inactivated mice to evaluate the role of β-arr1 or β-arr2 in platelet function, P2Y receptor desensitisation, haemostasis and thrombosis. Platelet aggregation, soluble fibrinogen binding and P-selectin exposure induced by various agonists were near normal in β-arr1−/− and β-arr2−/− platelets. In addition, deficiency in β-arr1 or β-arr2 was not critical for P2Y receptors desensitisation. A functional redundancy between β-arr1 and β-arr2 may explain these unchanged platelet responses. Interestingly, β-arr1−/− but not β-arr2−/− mice were protected against laser- and FeCl3-induced thrombosis. The tail bleeding times, number of rebleeds and volume of blood loss were unchanged in β-arr1−/− and β-arr2−/− mice, suggesting no defect in haemostasis. β-arr1−/− platelet activation upon adhesion to immobilised fibrinogen was inhibited, as attested by a 37 ± 5% (n = 3, p<0.0001) decrease in filopodia extension, suggesting defective signalling through integrin αIIbβ3. β-arr1 appeared to be located downstream of Src family kinases and to regulate αIIbβ3 signalling by increasing Akt phosphorylation. Overall, this study supports a role for β-arr1 in promoting thrombus formation, in part through its participation in αIIbβ3 signalling, and no role of β-arr1 and β-arr2 in agonist-induced platelet activation and P2Y receptors desensitisation.

scholarly journals Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors

2018 ◽  
Vol 19 (11) ◽  
pp. 3598 ◽  
Author(s):  
Mercedes Garcia-Gil ◽  
Marcella Camici ◽  
Simone Allegrini ◽  
Rossana Pesi ◽  
Edoardo Petrotto ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Purinergic Signaling ◽  
Adenosine Kinase ◽  
Synthesis Rate ◽  
Metabolizing Enzymes ◽  
And Function ◽  
Hypoxanthine Guanine Phosphoribosyl Transferase

The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5′-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function. Hypoxanthine guanine phosphoribosyl transferase (HPRT) appears to have a role in the purinosome formation and, therefore, in the regulation of purine synthesis rate during cell cycle with implications in brain development and tumors. The final product of purine catabolism, uric acid, also plays a recently highlighted novel role. In this review, we discuss the molecular mechanisms underlying the pathological manifestations of purine dysmetabolisms, focusing on the newly described/hypothesized roles of cytosolic 5′-nucleotidase II, adenosine kinase, adenosine deaminase, HPRT, and xanthine oxidase.

Metabolic acidosis in rats increases intestinal NHE2 and NHE3 expression and function

2002 ◽  
Vol 283 (1) ◽  
pp. G51-G56 ◽  
Author(s):  
Alvaro Lucioni ◽  
Christopher Womack ◽  
Mark W. Musch ◽  
Flavio L. Rocha ◽  
Cres Bookstein ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Ammonium Chloride ◽  
Brush Border ◽  
Cellular Differentiation ◽  
Mrna Levels ◽  
Northern Blots ◽  
Intestinal Physiology ◽  
Enhanced Expression ◽  
And Function

Chronic metabolic acidosis increases intestinal Na absorption, although through undefined mechanisms. Whether this occurs through enhanced expression and/or function of the brush-border Na+/H+ exchangers (NHE)2 and NHE3 is unknown. Metabolic acidosis was induced in rats by feeding ammonium chloride through their drinking water. Intestinal NHE activities were measured using brush-border 22Na+ uptake. Western and Northern blots measured changes in protein and mRNA expression, respectively. Acidosis occurred within 2 days of ammonium chloride feedings but increased after 6 days. NHE2 and NHE3 activities, protein expression, and mRNA levels increased in acidotic rats compared with controls. In contrast, basolateral NHE1 expression was not affected. Brush-border alkaline phosphatase showed no effect of metabolic acidosis on cellular differentiation. This study demonstrated a direct effect of metabolic acidosis on NHE2 and NHE3 activity, expression, and gene transcription. Metabolic acidosis is one of the few circumstances shown to affect NHE2 function and expression, thus providing insights into the role of NHE2 on intestinal physiology.

Expression and contribution of satellite glial cells purinoceptors to pain transmission in sensory ganglia: an update

2010 ◽  
Vol 6 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Giovanni Villa ◽  
Marta Fumagalli ◽  
Claudia Verderio ◽  
Maria P. Abbracchio ◽  
Stefania Ceruti
Keyword(s):  
Glial Cells ◽  
Pain Treatment ◽  
Purinergic Signaling ◽  
Original Data ◽  
P2y Receptors ◽  
Receptor Expression ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Pain Transmission

The role of adenosine-5′-triphosphate (ATP) and of the ligand-gated P2X3receptor in neuronal dorsal root ganglia (DRG) pain transmission is relatively well established. Much less is known about the purinergic system in trigeminal ganglia (TG), which are involved in certain types of untreatable neuropathic and inflammatory pain, as well as in migraine. Emerging data suggest that purinergic metabotropic P2Y receptors on both neurons and satellite glial cells (SGCs) may also participate in both physiological and pathological pain development. Here, we provide an updated literature review on the role of purinergic signaling in sensory ganglia, with special emphasis on P2Y receptors on SGCs. We also provide new original data showing a time-dependent downregulation of P2Y2and P2Y4receptor expression and function in purified SGCs cultures from TG, in comparison with primary mixed neuron–SGCs cultures. These data highlight the importance of the neuron–glia cross-talk in determining the SGCs phenotype. Finally, we show that, in mixed TG cultures, both adenine and guanosine induce intracellular calcium transients in neurons but not in SGCs, suggesting that also these purinergic-related molecules can participate in pain signaling. These findings may have relevant implications for the development of new therapeutic strategies for chronic pain treatment.

Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

1986 ◽  
Vol 44 ◽  
pp. 208-209
Author(s):  
Grace C.H. Yang
Keyword(s):  
Chick Embryo ◽  
Extracellular Space ◽  
Fibroblast Cell ◽  
Collagen Fibrils ◽  
Electron Microscopic ◽  
Voltage Electron ◽  
Scanning Electron Microscopic Study ◽  
Microscopic Studies ◽  
And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

Role of the Cilia Membrane in Control of Microtubule Sliding

1980 ◽  
Vol 38 ◽  
pp. 612-615
Author(s):  
Edna S. Kaneshiro
Keyword(s):  
Control Mechanism ◽  
Beat Frequency ◽  
Surface Membrane ◽  
Ciliary Membrane ◽  
Ciliary Beating ◽  
Ciliary Reversal ◽  
Voltage Dependent ◽  
Reversal Mechanism ◽  
And Function

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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