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Fanqi Kong, Bozhi Ye, Jiatian Cao, Xueli Cai, Lu Lin, Shanjun Huang, Weijian Huang, Zhouqing Huang
Aims: In the NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) inflammasome is closely related to the progression of atherosclerosis. This study aimed to assess the effects of curcumin on NLRP3 inflammasome in phorbol 12-myristate 13-acetate (PMA)-induced macrophages and explore its underlying mechanism. Methods: Human monocytic THP-1 cells were pretreated with curcumin for 1 h and subsequently induced with PMA for 48 h. Total protein was collected for Western blot analysis. Cytokine interleukin (IL)-1β release and nuclear factor kappa B (NF-κB) p65 translocation were detected by ELISA assay and cellular NF-κB translocation kit, respectively...
2016: Frontiers in Pharmacology
Csaba Vastagh, Annie Rodolosse, Norbert Solymosi, Zsolt Liposits
Gonadotropin-releasing hormone (GnRH) neurons play a key role in the central regulation of reproduction. In proestrous female mice, estradiol triggers the pre-ovulatory GnRH surge, however, its impact on the expression of neurotransmitter receptor genes in GnRH neurons has not been explored yet. We hypothesized that proestrus is accompanied by substantial changes in the expression profile of genes coding for neurotransmitter receptors in GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact, proestrous, and metestrous female GnRH-GFP transgenic mice, respectively...
2016: Frontiers in Cellular Neuroscience
Mengjie Lu, Beili Wu
G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y1 R and P2Y12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery...
October 20, 2016: IUBMB Life
Viktoria Hasselhof, Anastasia Sperling, Kerstin Buttler, Philipp Ströbel, Jürgen Becker, Thiha Aung, Gunther Felmerer, Jörg Wilting
Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1)...
2016: PloS One
Michael J Osgood, Kevin Sexton, Igor Voskresensky, Kyle Hocking, Jun Song, Padmini Komalavilas, Colleen Brophy, Joyce Cheung-Flynn
BACKGROUND: Intimal hyperplasia remains the primary cause of vein graft failure for the 1 million yearly bypass procedures performed using human saphenous vein (HSV) grafts. This response to injury is caused in part by the harvest and preparation of the conduit. The use of Brilliant Blue FCF (FCF) restores injury-induced loss of function in vascular tissues possibly via inhibition of purinergic receptor signaling. This study investigated whether pretreatment of the vein graft with FCF prevents intimal hyperplasia...
August 2016: Journal of Vascular Surgery
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
October 20, 2016: Glia
David Reigada, Rosa María Navarro-Ruiz, Marcos Javier Caballero-López, Ángela Del Águila, Teresa Muñoz-Galdeano, Rodrigo M Maza, Manuel Nieto-Díaz
Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap4A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes...
October 19, 2016: Purinergic Signalling
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
Jonathan M Beckel, Wennan Lu, Mortimer M Civan, Claire H Mitchell
No abstract text is available yet for this article.
October 2016: Journal of Ocular Pharmacology and Therapeutics
Andreas Reichenbach, Andreas Bringmann
Müller glia, the principal macroglia of the retina, express diverse subtypes of adenosine and metabotropic purinergic (P2Y) receptors. Müller cells of several species, including man, also express ionotropic P2X7 receptors. ATP is liberated from Müller cells after activation of metabotropic glutamate receptors and during osmotic and mechanical induction of membrane stretch; adenosine is released through equilibrative nucleoside transporters. Müller cell-derived purines modulate the neuronal activity and have autocrine effects, for example, induction of glial calcium waves and regulation of the cellular volume...
October 2016: Journal of Ocular Pharmacology and Therapeutics
Dmitry Mayorov, Sergey Kasparov, Julian Paton
OBJECTIVE: Functional defects in purinergic neurotransmission, and specifically adenosine A1 receptor, have been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Here, we examined the role of adenosine receptors in regulating cerebrovascular function in pre-hypertensive SHR. DESIGN AND METHOD: Changes in the diameter of pial arterioles (20-100 μm) in response to adenosine A1 and A2 receptor agonists were assessed after pre-constriction with the thromboxane agonist U46619 in slices from the brainstem and cortex of 4-6 week-old Wistar and SHR...
September 2016: Journal of Hypertension
Lien M Dos Santos, Tatiane M da Silva, Juliana H Azambuja, Priscila T Ramos, Pathise S Oliveira, Elita F da Silveira, Nathalia S Pedra, Kennia Galdino, Carlus A T do Couto, Mayara S P Soares, Rejane G Tavares, Roselia M Spanevello, Francieli M Stefanello, Elizandra Braganhol
Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established...
October 17, 2016: Molecular and Cellular Biochemistry
Weifeng Luo, Christy M Guth, Olukemi Jolayemi, Craig L Duvall, Colleen Marie Brophy, Joyce Cheung-Flynn
Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint, where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption...
2016: Frontiers in Bioengineering and Biotechnology
Satoru Koyanagi, Naoki Kusunose, Marie Taniguchi, Takahiro Akamine, Yuki Kanado, Yui Ozono, Takahiro Masuda, Yuta Kohro, Naoya Matsunaga, Makoto Tsuda, Michael W Salter, Kazuhide Inoue, Shigehiro Ohdo
Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn...
October 14, 2016: Nature Communications
Naiara Stefanello, Roberta Schmatz, Luciane Belmonte Pereira, Andréia Machado Cardoso, Sabina Passamonti, Rosélia Maria Spanevello, Gustavo Thomé, Giovanna Medeiros Tavares de Oliveira, Luiza Wilges Kist, Maurício Reis Bogo, Vera Maria Morsch, Maria Rosa Chitolina Schetinger
We evaluated the effect of chlorogenic acid (CGA), caffeine (CA) and coffee (CF) on components of the purinergic system from the cerebral cortex and platelets of streptozotocin-induced diabetic rats. Animals were divided into eight groups: control animals treated with (I) water (WT), (II) CGA (5 mg/kg), (III) CA (15 mg/kg) and (IV) CF (0.5 g/kg), and diabetic animals treated with (V) WT, (VI) CGA (5 mg/kg), (VII) CA (15 mg/kg) and (VIII) CF (0.5 g/kg). Our results showed an increase (173%) in adenosine monophosphate (AMP) hydrolysis in the cerebral cortex of diabetic rats...
September 22, 2016: Journal of Nutritional Biochemistry
Luiz Eduardo Baggio Savio, Mariana G Juste Andrade, Paola de Andrade Mello, Patrícia Teixeira Santana, Aline Cristina Abreu Moreira-Souza, Janaína Kolling, Aline Longoni, Linda Feldbrügge, Yan Wu, Angela T S Wyse, Simon C Robson, Robson Coutinho-Silva
Sepsis results in unfettered inflammation, tissue damage, and multiple organ failure. Diffuse brain dysfunction and neurological manifestations secondary to sepsis are termed sepsis-associated encephalopathy (SAE). Extracellular nucleotides, proinflammatory cytokines, and oxidative stress reactions are associated with delirium and brain injury, and might be linked to the pathophysiology of SAE. P2X7 receptor activation by extracellular ATP leads to maturation and release of IL-1β by immune cells, which stimulates the production of oxygen reactive species...
October 11, 2016: Molecular Neurobiology
Ryota Nakazato, Shogo Hotta, Daisuke Yamada, Miki Kou, Saki Nakamura, Yoshifumi Takahata, Hajime Tei, Rika Numano, Akiko Hida, Shigeki Shimba, Michihiro Mieda, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada
Similar to neurons, microglia have an intrinsic molecular clock. The master clock oscillator Bmal1 modulates interleukin-6 upregulation in microglial cells exposed to lipopolysaccharide. Bmal1 can play a role in microglial inflammatory responses. We previously demonstrated that gliotransmitter ATP induces transient expression of the clock gene Period1 via P2X7 purinergic receptors in cultured microglia. In this study, we further investigated mechanisms underlying the regulation of pro-inflammatory cytokine production by clock molecules in microglial cells...
October 11, 2016: Glia
Ryan L O'Hare Doig, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Sarah A Dunlop, Livia Hool, Melinda Fitzgerald
Combinations of Ca(2+) channel inhibitors have been proposed as an effective means to prevent excess Ca(2+) flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca(2+) concentrations. Here, the effects of combinations of Lomerizine (Lom), YM872, memantine and/or oxATP to block voltage gated Ca(2+) channels, Ca(2+) permeable AMPA receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca(2+) concentration and viability of primary mixed cortical cultures exposed to hydrogen peroxide (H2O2) insult, were assessed...
October 7, 2016: Neuroscience
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
Andrew Keech, Ute Vollmer-Conna, Benjamin K Barry, Andrew R Lloyd
Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterized by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signaling as an under-pinning of the fatigue state. A carefully-characterized sample of patients with CFS (N = 10) and healthy matched control participants (N = 12) were included. Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 h after 25 min of moderate-intensity cycling exercise...
2016: Frontiers in Physiology
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