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https://www.readbyqxmd.com/read/28004813/electrical-stimulation-drives-chondrogenesis-of-mesenchymal-stem-cells-in-the-absence-of-exogenous-growth-factors
#1
Hyuck Joon Kwon, Gyu Seok Lee, Honggu Chun
Electrical stimulation (ES) is known to guide the development and regeneration of many tissues. However, although preclinical and clinical studies have demonstrated superior effects of ES on cartilage repair, the effects of ES on chondrogenesis remain elusive. Since mesenchyme stem cells (MSCs) have high therapeutic potential for cartilage regeneration, we investigated the actions of ES during chondrogenesis of MSCs. Herein, we demonstrate for the first time that ES enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels, thereby inducing differentiation of MSCs into hyaline chondrogenic cells without the addition of exogenous growth factors...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28004778/glycosides-from-edible-sea-cucumbers-stimulate-macrophages-via-purinergic-receptors
#2
Dmitry Aminin, Evgeny Pislyagin, Maxim Astashev, Andrey Es'kov, Valery Kozhemyako, Sergei Avilov, Elena Zelepuga, Ekaterina Yurchenko, Leonid Kaluzhskiy, Emma Kozlovskaya, Alexis Ivanov, Valentin Stonik
Since ancient times, edible sea cucumbers have been considered a jewel of the seabed and used in Asian folk medicine for stimulation of resistance against different diseases. However, the power of this sea food has not been established on a molecular level. A particular group of triterpene glycosides was found to be characteristic metabolites of the animals, responsible for this biological action. Using one of them, cucumarioside A2-2 (CA2-2) from the edible Cucumaria japonica species as an example as well as inhibitory analysis, patch-clamp on single macrophages, small interfering RNA technique, immunoblotting, SPR analysis, computer modeling and other methods, we demonstrate low doses of CA2-2 specifically to interact with P2X receptors (predominantly P2X4) on membranes of mature macrophages, enhancing the reversible ATP-dependent Ca(2+) intake and recovering Ca(2+) transport at inactivation of these receptors...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28002740/the-dynamic-behavior-of-the-p2x4-ion-channel-in-the-closed-conformation
#3
Gustavo Pierdominici-Sottile, Luciano Moffatt, Juliana Palma
We present the results of a detailed molecular dynamics study of the closed form of the P2X4 receptor. The fluctuations observed in the simulations were compared with the changes that occur in the transition from the closed to the open structure. To get further insight on the opening mechanism, the actual displacements were decomposed into interchain motions and intrachain deformations. This analysis revealed that the iris-like expansion of the transmembrane helices mainly results from interchain motions that already take place in the closed conformation...
December 20, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27999370/effect-of-lead-pb-on-inflammatory-processes-in-the-brain
#4
REVIEW
Karina Chibowska, Irena Baranowska-Bosiacka, Anna Falkowska, Izabela Gutowska, Marta Goschorska, Dariusz Chlubek
That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7...
December 19, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27988461/divergent-regulatory-roles-of-extracellular-atp-in-the-degranulation-response-of-mouse-bone-marrow-derived-mast-cells
#5
Kazuki Yoshida, Masaaki Ito, Isao Matsuoka
Mast cells (MCs) play a critical role in allergic inflammation. Although purinergic signalling is implicated in the regulation of various immune responses, its role in MC function is not fully understood. In this study, we investigated the regulatory role of purinergic signalling in MC degranulation, using mouse bone marrow-derived mast cells (BMMCs). Notably, BMMCs expressed various functional P2 adenosine triphosphate (ATP) receptors, including ionotropic P2X4 and P2X7, involved in the regulation of BMMC degranulation...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27867013/characterization-of-p2x4-receptor-agonists-and-antagonists-by-calcium-influx-and-radioligand-binding-studies
#6
Aliaa Abdelrahman, Vigneshwaran Namasivayam, Sonja Hinz, Anke C Schiedel, Meryem Köse, Maggi Burton, Ali El-Tayeb, Michel Gillard, Jürgen Bajorath, Marc de Ryck, Christa E Müller
Antagonists for ATP-activated P2X4 ion channel receptors are currently in the focus as novel drug targets, in particular for the treatment of neuropathic and inflammatory pain. We stably expressed the human, rat and mouse P2X4 receptors in 1321N1 astrocytoma cells, which is devoid of functional nucleotide receptors, by retroviral transfection, and established monoclonal cell lines. Calcium flux assay conditions were optimized for high-throughput screening resulting in a Z'-factor of >0.8. The application of ready-to-use frozen cells did not negatively affect the results of the calcium assays, which is of great advantage for the screening of compound libraries...
November 17, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27823931/two-p2x1-receptor-transcripts-able-to-form-functional-channels-are-present-in-most-human-monocytes
#7
Cintya López-López, Josue Jaramillo-Polanco, Diana P Portales-Pérez, Karen S Gómez-Coronado, Jessica G Rodríguez-Meléndez, Juan D Cortés-García, Rosa Espinosa-Luna, Luis M Montaño, Carlos Barajas-López
To characterize the presence and general properties of P2X1 receptors in single human monocytes we used RT-PCR, flow cytometry, and the patch-clamp and the two-electrode voltage-clamp techniques. Most human monocytes expressed the canonical P2X1 (90%) and its splicing variant P2X1del (88%) mRNAs. P2X1 receptor immunoreactivity was also observed in 70% of these cells. Currents mediated by P2X1 (EC50=1.9±0.8µm) and P2X1del (EC50 >1000µm) channels, expressed in Xenopus leavis oocytes, have different ATP sensitivity and kinetics...
December 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27768754/duloxetine-inhibits-microglial-p2x4-receptor-function-and-alleviates-neuropathic-pain-after-peripheral-nerve-injury
#8
Tomohiro Yamashita, Shota Yamamoto, Jiaming Zhang, Miho Kometani, Daisuke Tomiyama, Keita Kohno, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R...
2016: PloS One
https://www.readbyqxmd.com/read/27640997/atp-from-synaptic-terminals-and-astrocytes-regulates-nmda-receptors-and-synaptic-plasticity-through-psd-95-multi-protein-complex
#9
U Lalo, O Palygin, A Verkhratsky, S G N Grant, Y Pankratov
Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca(2+)-dependent mechanism...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27576299/a-novel-p2x4-receptor-selective-antagonist-produces-anti-allodynic-effect-in-a-mouse-model-of-herpetic-pain
#10
Yuta Matsumura, Tomohiro Yamashita, Atsushi Sasaki, Eriko Nakata, Keita Kohno, Takahiro Masuda, Hidetoshi Tozaki-Saitoh, Toshiyasu Imai, Yasushi Kuraishi, Makoto Tsuda, Kazuhide Inoue
Accumulating evidence indicates that purinergic P2X4 receptors (P2X4R: cation channels activated by extracellular ATP) expressed in spinal microglia are crucial for pathological chronic pain caused by nerve damage, suggesting a potential target for drug discovery. We identified NP-1815-PX (5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1, 2-b][1,4]diazepine-2,4(3H,5H)-dione) as a novel antagonist selective for P2X4R with high potency and selectivity compared with other P2XR subtypes. In in vivo assay for acute and chronic pain, intrathecal administration of NP-1815-PX produced an anti-allodynic effect in mice with traumatic nerve damage without affecting acute nociceptive pain and motor function (although its oral administration did not produce the effect)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27576209/effects-of-adenosine-triphosphate-on-proliferation-and-odontoblastic-differentiation-of%C3%A2-human-dental-pulp-cells
#11
Wei Wang, Xiaosong Yi, Yanfang Ren, Qiufei Xie
INTRODUCTION: Adenosine 5'-triphosphate (ATP) is a potent signaling molecule that regulates diverse biological activities in cells. Its effects on human dental pulp cells (HDPCs) remain unknown. This study aimed to examine the effects of ATP on proliferation and differentiation of HDPCs. METHODS: Reverse transcription polymerase chain reaction was performed to explore the mRNA expression of P2 receptor subtypes. Cell Counting Kit-8 test and flow cytometry analysis were used to examine the effects of ATP on proliferation and cell cycle of HDPCs...
October 2016: Journal of Endodontics
https://www.readbyqxmd.com/read/27559172/p2x4-receptor-reporter-mice-sparse-brain-expression-and-feeding-related-presynaptic-facilitation-in-the-arcuate-nucleus
#12
Ji Xu, Alexander M Bernstein, Angela Wong, Xiao-Hong Lu, Sheraz Khoja, X William Yang, Daryl L Davies, Paul Micevych, Michael V Sofroniew, Baljit S Khakh
UNLABELLED: P2X4 receptors are ATP-gated cation channels that are widely expressed in the nervous system. To identify P2X4 receptor-expressing cells, we generated BAC transgenic mice expressing tdTomato under the control of the P2X4 receptor gene (P2rx4). We found sparse populations of tdTomato-positive neurons in most brain areas with patterns that matched P2X4 mRNA distribution. tdTomato expression within microglia was low but was increased by an experimental manipulation that triggered microglial activation...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27545450/differential-gene-expression-patterns-and-colocalization-of-atp-gated-p2x6-p2x4-ion-channels-during-rat-small-intestine-ontogeny
#13
Karla Padilla, David Gonzalez-Mendoza, Laura C Berumen, Jesica E Escobar, Ricardo Miledi, Guadulupe García-Alcocer
Gene coding for ATP-gated receptor ion channels (P2X1-7) has been associated with the developmental process in various tissues; among these ion channel subtypes, P2X6 acts as a physiological regulator of P2X4 receptor functions when the two receptors form heteroreceptors. The P2X4 receptor is involved in pain sensation, the inflammatory process, and body homeostasis by means of Mg(2+) absorption through the intestine. The small intestine is responsible for the absorption and digestion of nutrients; throughout its development, several gene expressions are induced that are related to nutrients received, metabolism, and other intestine functions...
July 2016: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/27526181/ionotropic-purinergic-receptors-p2x4-and-p2x7-proviral-or-antiviral-an-insight-into-p2x-receptor-signaling-and-hepatitis-c-virus-infection
#14
Sobia Manzoor, Umair Akhtar, Sidrah Naseem, Madiha Khalid, Misha Mazhar, Fahed Parvaiz, Saba Khaliq
Purinergic P2X receptors are plasma membrane bound, ATP-gated ion channels that are expressed on wide range of cells and respond to varying ATP concentrations in extracellular environment. Upon activation they increase membrane permeability for Ca(2+) ions and trigger a cascade of signaling complexes. During the course of hepatitis C virus (HCV) infection, ATP is released from the infected hepatocyte, which binds with Purinergic receptors (P2X) on peripheral blood mononuclear cells (PBMCs) and initiate downstream signaling pathways by disturbing the ionic balance of the cell...
September 2016: Viral Immunology
https://www.readbyqxmd.com/read/27506813/morphine-enhances-il-1%C3%AE-release-through-toll-like-receptor-4-mediated-endocytic-pathway-in-microglia
#15
Yongxin Liang, Haichen Chu, Yanan Jiang, Li Yuan
Morphine creates a neuroinflammatory response and enhances release of the proinflammatory cytokines like interleukin-1β (IL-1β), which compromises morphine analgesia as well as induces morphine tolerance. In this study, we attempted to investigate the mechanisms of morphine induced IL-1β synthesis and release. Microglial cells were treated with morphine (100 μM) once daily for 3 days. Control groups underwent the same procedure but received sterile saline injection instead of morphine. Toll-like receptor 4 (TLR4) and P2X4 receptor (P2X4R) signaling were analyzed using Western blot; immunofluorescence was used to detect the signaling of CD68; real-time RT-PCR and ELISA kit was used to measure the messenger RNA and protein synthesis and release level of IL-1β...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27477609/activation-of-lysosomal-p2x4-by-atp-transported-into-lysosomes-via-vnut-slc17a9-using-v-atpase-generated-voltage-gradient-as-the-driving-force
#16
Xi Zoë Zhong, Qi Cao, Xue Sun, Xian-Ping Dong
KEY POINTS: SLC17A9 proteins function as a lysosomal ATP transporter responsible for lysosomal ATP accumulation. P2X4 receptors act as lysosomal ion channels activated by luminal ATP. SLC17A9-mediated ATP transport across the lysosomal membrane is suppressed by Bafilomycin A1, the V-ATPase inhibitor. SLC17A9 mainly uses voltage gradient but not pH gradient generated by the V-ATPase as the driving force to transport ATP into the lysosome to activate P2X4. ABSTRACT: The lysosome contains abundant ATP which plays important roles in lysosome functions and in cell signalling...
August 1, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27453058/down-regulation-of-purinergic-p2x7-receptor-expression-and-intracellular-calcium-dysregulation-in-peripheral-blood-mononuclear-cells-of-patients-with-amyotrophic-lateral-sclerosis
#17
Jingyu Liu, Tino Prell, Beatrice Stubendorff, Silke Keiner, Thomas Ringer, Anne Gunkel, Vedrana Tadic, Nadine Goldhammer, Ayse Malci, Otto W Witte, Julian Grosskreutz
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with intracellular Ca(2+) dysregulation. The P2X receptor family is comprised of ligand-gated ion channels that respond to extracellular adenosine triphosphate (ATP) and increases permeability of calcium into the cell. The underlying mechanisms of purinergic signalling on peripheral blood mononuclear cells (PBMCs) in ALS remain unclear. Herein, we studied the expression of P2X4/P2X7 receptors and calcium homeostasis in blood cells of ALS patients...
September 6, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27402173/role-of-purinergic-p2x4-receptors-in-regulating-striatal-dopamine-homeostasis-and-dependent-behaviors
#18
Sheraz Khoja, Vivek Shah, Damaris Garcia, Liana Asatryan, Michael W Jakowec, Daryl L Davies
Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ion channels regulated by ATP. We recently demonstrated that P2X4R knockout (KO) mice exhibited deficits in sensorimotor gating, social interaction, and ethanol drinking behavior. Dopamine (DA) dysfunction may underlie these behavioral changes, but there is no direct evidence for P2X4Rs' role in DA neurotransmission. To test this hypothesis, we measured markers of DA function and dependent behaviors in P2X4R KO mice. P2X4R KO mice exhibited altered density of pre-synaptic markers including tyrosine hydroxylase, dopamine transporter; post-synaptic markers including dopamine receptors and phosphorylation of downstream targets including dopamine and cyclic-AMP regulated phosphoprotein of 32 kDa and cyclic-AMP-response element binding protein in different parts of the striatum...
October 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27400972/a-central-role-for-atp-signalling-in-glial-interactions-in-the-cns
#19
Andrea Rivera, Ilaria Vanzulli, Arthur M Butt
The purine ATP has a prominent regulatory role in CNS function and pathology due to its actions on glial cells - microglia, astrocytes and oligodendrocytes. ATP serves as an apparently ubiquitous 'gliotransmitter' that is released by astrocytes and other cells to activate purine receptors on neighbouring cells. In pathology, the release of ATP mediates both tissue damage and repair by its direct effects on glial cell integrity and survival. The actions of ATP on glia are mediated via a wide range of receptors, broadly divided into ionotropic P2X and metabotropic (G-protein coupled receptors (GPCR)) P2Y receptors, of which there are multiple subtypes (P2X1-P2X7 and P2Y1-P2Y14)...
2016: Current Drug Targets
https://www.readbyqxmd.com/read/27301647/the-p2x4-purinergic-receptor-impacts-liver-regeneration-after-partial-hepatectomy-in-mice-through-the-regulation-of-biliary-homeostasis
#20
Aurore Besnard, Julien Gautherot, Boris Julien, Ali Tebbi, Isabelle Garcin, Isabelle Doignon, Noémie Péan, Emmanuel Gonzales, Doris Cassio, Brigitte Grosse, Bingkaï Liu, Hanaa Safya, Florent Cauchois, Lydie Humbert, Dominique Rainteau, Thierry Tordjmann
UNLABELLED: Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH), to initiate growth, protect liver cells, and sustain remnant liver functions. Extracellular adenosine triphosphate rises in blood and bile after PH and contributes to liver regeneration, although purinergic receptors and mechanisms remain to be precisely explored. In this work we analyzed during regeneration after PH the involvement of P2X4 purinergic receptors, highly expressed in the liver...
September 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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