Read by QxMD icon Read


Hongbo Hu, Baohui Yang, Yumin Li, Subin Zhang, Zheng Li
P2X purinoceptor 7 (P2X7) receptor (P2X7R) is known to play a significant role in inflammation and pain-causing diseases, including osteoarthritis (OA). However, the mechanisms of action of P2X7R and its role in OA remain unclear. The articular cartilage is the crucial region in which pathological changes occur in OA, involving the dysregulation of degradation and maintenance mechanisms. In this study, we aimed to reveal the molecular mechanisms of action of P2X7R in articular cartilage in OA-induced pain and inflammation by using AZD9056, an antagonist of P2X7R...
October 13, 2016: International Journal of Molecular Medicine
Jin-Hee Park, Yong-Chul Kim
The P2X7 receptor (P2X7R) is a unique subtype among the family of seven purinergic P2X receptors, which are ATP-gated non-selective cation channels. P2X7R has been reported to have pathological roles in various diseases, including autoimmune diseases such as arthritis and inflammatory bowel disease, neurodegenerative diseases, chronic pain, mood disorders and cancers. Therefore, many pharmaceutical companies have endeavored to develop a clinical candidate targeting P2X7R. Areas covered: This review provides a summary of various patents on chemicals and biologics and their clinical use published between 2010 and 2015...
October 10, 2016: Expert Opinion on Therapeutic Patents
Sho Ichinohe, Toshiyuki Ishii, Hiroshi Takahashi, Makoto Kaneda
ATP activates P2X receptors and acts as a neurotransmitter in the nervous system. We have previously reported that P2X receptors modulate the firing rate of retinal ganglion cells. Since many subtypes of P2X receptors are distributed in the mouse retina, it is likely that the modulatory effects of P2X receptor-mediated signaling can occur at multiple synaptic levels in the retina. In this study, we investigated whether P2X receptors expressed between the photoreceptor layer and the inner nuclear layer in the mouse retina were physiologically functional, by electroretinography (ERG)...
October 5, 2016: Neuroscience Research
Marta Kuczeriszka, Leszek Dobrowolski, Agnieszka Walkowska, Janusz Sadowski
BACKGROUND: Purine P2X and P2Y receptors (P2-R) are involved in control of renal circulation, especially in the medulla, wherein they appear to interact with angiotensin II (Ang II). Our experimental approach enabled examination of interaction with Ang II per se, in the absence of blood pressure elevation. In this whole-kidney functional study we focused on the influence of P2X1-R on perfusion of the renal medulla. METHODS: Acute experiments were conducted with normal rats, untreated or subjected to two weeks' infusion of Ang II (osmotic minipumps)...
August 1, 2016: Pharmacological Reports: PR
Ivan Tochitsky, Zachary Helft, Victor Meseguer, Russell B Fletcher, Kirstan A Vessey, Michael Telias, Bristol Denlinger, Jonatan Malis, Erica L Fletcher, Richard H Kramer
Azobenzene photoswitches confer light sensitivity onto retinal ganglion cells (RGCs) in blind mice, making these compounds promising candidates as vision-restoring drugs in humans with degenerative blindness. Remarkably, photosensitization manifests only in animals with photoreceptor degeneration and is absent from those with intact rods and cones. Here we show that P2X receptors mediate the entry of photoswitches into RGCs, where they associate with voltage-gated ion channels, enabling light to control action-potential firing...
October 5, 2016: Neuron
Qian Gao, Hanxiao Ren, Mingkun Chen, Ziguang Niu, Haibo Tao, Yin Jia, Jianrong Zhang, Wenjie Li
β-crystallin B2 (CRYBB2) knockout mice exhibit morphological and functional abnormalities in the ovary. Long non‑coding RNAs (lncRNAs) regulate gene transcription and translation, and epigenetic modification of genomic DNA. The present study investigated the role of lncRNAs in mediating the effects of CRYBB2 in the regulation of ovary development in mice. In the current study, ovary tissues from wild‑type (WT) and CRYBB2 knockout mice were subjected to lncRNA and mRNA microarray profiling. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to group the differentially expressed lncRNAs into regulated gene pathways and functions...
September 22, 2016: Molecular Medicine Reports
Saskia Maria Burm, Ella Alwine Zuiderwijk-Sick, Paola Massiel Weert, Jeffrey John Bajramovic
Under stressful conditions nucleotides are released from dying cells into the extracellular space, where they can bind to purinergic P2X and P2Y receptors. High concentrations of extracellular ATP in particular induce P2X7-mediated signaling, which leads to inflammasome activation. This in turn leads to the processing and secretion of pro-inflammatory cytokines, like interleukin (IL)-1β. During neurodegenerative diseases, innate immune responses are shaped by microglia and we have previously identified microglia-specific features of inflammasome-mediated responses...
September 19, 2016: Glia
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
Elina Välimäki, Wojciech Cypryk, Juhani Virkanen, Katariina Nurmi, Pauli M Turunen, Kari K Eklund, Karl E Åkerman, Tuula A Nyman, Sampsa Matikainen
Extracellular ATP is an endogenous danger signal that is known to activate inflammatory responses in innate immune cells, including macrophages. Activated macrophages start to secrete proteins to induce an immune response, as well as to recruit other immune cells to the site of infection and tissue damage. In this study, we characterized the secretome (i.e., the global pattern of secreted proteins) of ATP-stimulated human macrophages. We show that ATP stimulation activates robust vesicle-mediated unconventional protein secretion, including exosome release and membrane shedding, from human macrophages...
September 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yong Tang, Peter Illes
Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes...
September 15, 2016: Glia
Steven E Mansoor, Wei Lü, Wout Oosterheert, Mrinal Shekhar, Emad Tajkhorshid, Eric Gouaux
P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states...
September 14, 2016: Nature
Johan-Till Pougnet, Benjamin Compans, Audrey Martinez, Daniel Choquet, Eric Hosy, Eric Boué-Grabot
Plasticity at excitatory synapses can be induced either by synaptic release of glutamate or the release of gliotransmitters such as ATP. Recently, we showed that postsynaptic P2X2 receptors activated by ATP released from astrocytes downregulate synaptic AMPAR, providing a novel mechanism by which glial cells modulate synaptic activity. ATP- and lNMDA-induced depression in the CA1 region of the hippocampus are additive, suggesting distinct molecular pathways. AMPARs are homo-or hetero-tetramers composed of GluA1-A4...
2016: Scientific Reports
Alistair G Fryatt, Sudad Dayl, Paul M Cullis, Ralf Schmid, Richard J Evans
Structural studies of P2X receptors show a novel U shaped ATP orientation following binding. We used voltage clamp fluorometry (VCF) and molecular dynamics (MD) simulations to investigate agonist action. For VCF the P2X1 receptor (P2X1R) K190C mutant (adjacent to the agonist binding pocket) was labelled with the fluorophore MTS-TAMRA and changes in fluorescence on agonist treatment provided a real time measure of conformational changes. Studies with heteromeric channels incorporating a key lysine mutation (K68A) in the ATP binding site demonstrate that normally three molecules of ATP activate the receptor...
2016: Scientific Reports
Kenneth A Jacobson, Mortimer M Civan
Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A1, A2A, and A3...
October 2016: Journal of Ocular Pharmacology and Therapeutics
Steen K Fagerberg, Martin R Jakobsen, Marianne Skals, Helle A Praetorius
α-hemolysin (HlyA) from Escherichia coli and leukotoxin A (LtxA) from Aggregatibacter actinomycetemcomitans are important virulence factors in ascending urinary tract infections and aggressive periodontitis, respectively. The extracellular signaling molecule ATP is released immediately after insertion of the toxins into plasma membranes and is via P2X receptors essential for the erythrocyte damage inflicted by these toxins. Moreover, ATP signaling is required for the following recognition and phagocytosis of damaged erythrocytes by the monocytic cell line THP-1...
August 15, 2016: Infection and Immunity
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
Shu Xing, Matthew W Grol, Peter H Grutter, S Jeffrey Dixon, Svetlana V Komarova
Extracellular ATP acts on the P2X family of ligand-gated ion channels and several members of the P2Y family of G protein-coupled receptors to mediate intercellular communication among many cell types including bone-forming osteoblasts. It is known that multiple P2 receptors are expressed on osteoblasts (P2X2,5,6,7 and P2Y1,2,4,6). In the current study, we investigated complex interactions within the P2 receptor network using mathematical modeling. To characterize individual P2 receptors, we extracted data from published studies of overexpressed human and rodent (rat and mouse) receptors and fit their dependencies on ATP concentration using the Hill equation...
2016: Frontiers in Physiology
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
Hao Li, Haowen Li, Yajing Hao, Yuming Jiao, Zhicen Li, Haiyan Yue, Zhe Xu, Shuo Wang, Yong Cao, Jizong Zhao
Differentiation of glioblastoma stem cells (GSCs) may lead to inhibition of their self‑renewing ability and tumorigenic potential, as well as increasing their sensitivity to treatment. The critical role of long non‑coding RNAs (lncRNAs) in numerous biological processes has been revealed. However, the involvement of lncRNAs in GSC differentiation remains to be elucidated. In the present study, GSCs were isolated from patient samples and differentiation was induced. Using a high‑throughput microarray, the present study identified a profile of 1,545 lncRNAs and 2,729 mRNAs that differed between GSCs and their non‑differentiated counterparts...
September 2016: Molecular Medicine Reports
Maurish Bukhari, Hayley Burm, Damien S K Samways
Ionic "vital dyes" are commonly used to assess cell viability based on the idea that their permeation is contingent on a loss of membrane integrity. However, the possibility that dye entry is conducted into live cells by endogenous membrane transporters must be recognized and controlled for. Several cation-selective plasma membrane-localized ion channels, including the adenosine 5'-triphosphate (ATP)-gated P2X receptors, have been reported to conduct entry of the DNA-binding fluorescence dye, YO-PRO-1, into live cells...
October 2016: Cell Biology and Toxicology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"