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TRPA1 ion channel

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https://www.readbyqxmd.com/read/29038531/trpa1-fgfr2-binding-event-is-a-regulatory-oncogenic-driver-modulated-by-mirna-142-3p
#1
Jonathan Berrout, Eleni Kyriakopoulou, Lavanya Moparthi, Alexandra S Hogea, Liza Berrout, Cristina Ivan, Mihaela Lorger, John Boyle, Chris Peers, Stephen Muench, Jacobo Elies Gomez, Xin Hu, Carolyn Hurst, Thomas Hall, Sujanitha Umamaheswaran, Laura Wesley, Mihai Gagea, Michael Shires, Iain Manfield, Margaret A Knowles, Simon Davies, Klaus Suhling, Yurema Teijeiro Gonzalez, Neil Carragher, Kenneth Macleod, N Joan Abbott, George A Calin, Nikita Gamper, Peter M Zygmunt, Zahra Timsah
Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29034461/the-migraine-attack-as-a-homeostatic-neuroprotective-response-to-brain-oxidative-stress-preliminary-evidence-for-a-theory
#2
Jonathan M Borkum
BACKGROUND: Previous research has suggested that migraineurs show higher levels of oxidative stress (lipid peroxides) between migraine attacks and that migraine triggers may further increase brain oxidative stress. Oxidative stress is transduced into a neural signal by the TRPA1 ion channel on meningeal pain receptors, eliciting neurogenic inflammation, a key event in migraine. Thus, migraines may be a response to brain oxidative stress. RESULTS: In this article, a number of migraine components are considered: cortical spreading depression, platelet activation, plasma protein extravasation, endothelial nitric oxide synthesis, and the release of serotonin, substance P, calcitonin gene-related peptide, and brain-derived neurotrophic factor...
October 16, 2017: Headache
https://www.readbyqxmd.com/read/28986540/reactive-metabolites-of-acetaminophen-activate-and-sensitize-the-capsaicin-receptor-trpv1
#3
Mirjam J Eberhardt, Florian Schillers, Esther M Eberhardt, Linus Risser, Jeanne de la Roche, Christine Herzog, Frank Echtermeyer, Andreas Leffler
The irritant receptor TRPA1 was suggested to mediate analgesic, antipyretic but also pro-inflammatory effects of the non-opioid analgesic acetaminophen, presumably due to channel activation by the reactive metabolites parabenzoquinone (pBQ) and N-acetyl-parabenzoquinonimine (NAPQI). Here we explored the effects of these metabolites on the capsaicin receptor TRPV1, another redox-sensitive ion channel expressed in sensory neurons. Both pBQ and NAPQI, but not acetaminophen irreversibly activated and sensitized recombinant human and rodent TRPV1 channels expressed in HEK 293 cells...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935134/sites-contributing-to-trpa1-activation-by-the-anesthetic-propofol-identified-by-photoaffinity-labeling
#4
Kellie A Woll, Kenneth A Skinner, Eleonora Gianti, Natarajan V Bhanu, Benjamin A Garcia, Vincenzo Carnevale, Roderic G Eckenhoff, Rachelle Gaudet
In addition to inducing anesthesia, propofol activates a key component of the pain pathway, the transient receptor potential ankyrin 1 ion channel (TRPA1). Recent mutagenesis studies suggested a potential activation site within the transmembrane domain, near the A-967079 cavity. However, mutagenesis cannot distinguish between protein-based and ligand-based mechanisms, nor can this site explain the complex modulation by propofol. Thus more direct approaches are required to reveal potentially druggable binding sites...
September 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#5
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28891864/photosensitization-of-trpa1-and-trpv1-by-7-dehydrocholesterol-implications-for-the-smith-lemli-opitz-syndrome
#6
Alexandru Babes, Cosmin I Ciotu, Tal Hoffmann, Tatjana I Kichko, Tudor Selescu, Cristian Neacsu, Susanne K Sauer, Peter W Reeh, Michael J M Fischer
Loss-of-function mutations in the enzyme 7-dehydrocholesterol reductase are responsible for the Smith-Lemli-Opitz syndrome, in which 7-dehydrocholesterol (7-DHC) levels are markedly increased in the plasma and tissues of patients. This increase in 7-DHC is probably associated with the painful and itchy photosensitivity reported by the majority of patients with Smith-Lemli-Opitz syndrome. To identify the molecular targets involved in the activation and photosensitization of primary afferents by 7-DHC, we focused on TRPA1 and TRPV1, two ion channels expressed in nociceptive nerve endings and previously shown to respond to ultraviolet and visible light under pathophysiological circumstances...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#7
Holger Beckmann, Julia Richter, Kerstin Hill, Nicole Urban, Horst Lemoine, Michael Schaefer
The transient receptor potential canonical channel 5 (TRPC5) is a Ca(2+)-permeable ion channel, which is predominantly expressed in the brain. TRPC5-deficient mice exhibit a reduced innate fear response and impaired motor control. In addition, outgrowth of hippocampal and cerebellar neurons is retarded by TRPC5. However, pharmacological evidence of TRPC5 function on cellular or organismic levels is sparse. Thus, there is still a need for identifying novel and efficient TRPC5 channel modulators. We, therefore, screened compound libraries and identified the glucocorticoid methylprednisolone and N-[3-(adamantan-2-yloxy)propyl]-3-(6-methyl-1,1-dioxo-2H-1λ(6),2,4-benzothiadiazin-3-yl)propanamide (BTD) as novel TRPC5 activators...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28799666/effect-of-resveratrol-on-c-fos-expression-of-rat-trigeminal-spinal-nucleus-caudalis-and-c1-dorsal-horn-neurons-following-mustard-oil-induced-acute-inflammation
#8
Yasuhiro Matsumoto, Kyouhei Komatsu, Yoshihito Shimazu, Shiori Takehana, Yumiko Syouji, Ayumu Kobayashi, Mamoru Takeda
The dietary constituent, resveratrol, was recently identified as a transient receptor potential ankyrin 1 (TRPA1) antagonist, voltage-dependent sodium ion (Na(+) ) channel, and cyclooxygenase-2 (COX-2) inhibitor. The aim of the present study was to investigate whether pretreatment with resveratrol attenuates acute inflammation-induced sensitization of nociceptive processing in rat spinal trigeminal nucleus caudalis (SpVc) and upper cervical (C1) dorsal horn neurons, via c-fos immunoreactivity. Mustard oil (MO), a TRPA1 channel agonist, was injected into the whisker pads of rats to induce inflammation...
August 11, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/28792844/trpa1-ion-channel-stimulation-enhances-cardiomyocyte-contractile-function-via-a-camkii-dependent-pathway
#9
Spencer R Andrei, Monica Ghosh, Pritam Sinharoy, Souvik Dey, Ian N Bratz, Derek S Damron
RATIONALE: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. OBJECTIVE: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action...
August 9, 2017: Channels
https://www.readbyqxmd.com/read/28757246/evaluation-of-mesenchymal-stem-cell-modulation-of-trigeminal-neuronal-responses-to-cold
#10
Michael A Eskander, Koyo Takimoto, Anibal Diogenes
Tissue engineering protocols, such as regenerative endodontic procedures (REPs), comprise biologically based procedures designed to restore normal physiologic function. For REPs, the goal is reconstitution of the pulp-dentin complex by delivering mesenchymal stem cells (MSCs), including the stem cells of the apical papilla (SCAP) into a root canal system. Many patients regain cold sensitivity after REPs, but the mechanism is not understood. We hypothesized that SCAP modulate nociceptive function through a paracrine mechanism that activates cold-sensitive ion channels in neurons...
July 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28732812/extracts-and-compounds-active-on-trp-ion-channels-from-waldheimia-glabra-a-ritual-medicinal-plant-from-himalaya
#11
Annamaria Giorgi, Angela Bassoli, Gigliola Borgonovo, Sara Panseri, Alessandra Manzo, Daniela Pentimalli, Aniello Schiano Moriello, Luciano De Petrocellis
BACKGROUND: Waldheimia glabra (Decne.) Regel is a wild plant from the Himalayan Mountains, commonly known as Smooth Ground Daisy. This plant is traditionally used by local populations in religious rituals (incense) or in traditional herbal medicine to treat skin diseases, headache, joint pain and fever. In literature few data are available on the investigation of this aromatic plant. PURPOSE: The present work aims at deepening knowledge about the chemical composition of W...
August 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28730837/molecular-basis-of-trpa1-regulation-in-nociceptive-neurons-a-review
#12
A Kádková, V Synytsya, J Krusek, L Zímová, V Vlachová
Transient receptor potential A1 (TRPA1) is an excitatory ion channel that functions as a cellular sensor, detecting a wide range of proalgesic agents such as environmental irritants and endogenous products of inflammation and oxidative stress. Topical application of TRPA1 agonists produces an acute nociceptive response through peripheral release of neuropeptides, purines and other transmitters from activated sensory nerve endings. This, in turn, further regulates TRPA1 activity downstream of G-protein and phospholipase C-coupled signaling cascades...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28680930/evolutionary-tuning-of-trpa1-and-trpv1-thermal-and-chemical-sensitivity-in-vertebrates
#13
REVIEW
Shigeru Saito, Makoto Tominaga
Thermal perception is an essential sensory system for survival since temperature fluctuations affect various biologic processes. Therefore, evolutionary changes in thermosensory systems may have played important roles in adaptation processes. Comparative analyses of sensory receptors among different species can provide us with important clues to understand the molecular basis for adaptation. Several ion channels belonging to the transient receptor potential (TRP) superfamily serve as thermal sensors in a wide variety of animal species...
2017: Temperature: Multidisciplinary Biomedical Journal
https://www.readbyqxmd.com/read/28669932/cough-and-airway-disease-the-role-of-ion-channels
#14
REVIEW
Sara J Bonvini, Maria G Belvisi
Cough is the most common reason for patients to visit a primary care physician, yet it remains an unmet medical need. It can be idiopathic in nature but can also be a troublesome symptom across chronic lung diseases such as asthma, COPD and idiopathic pulmonary fibrosis (IPF). Chronic cough affects up to 12% of the population and yet there are no safe and effective therapies. The cough reflex is regulated by vagal, sensory afferent nerves which innervate the airway. The Transient Receptor Potential (TRP) family of ion channels are expressed on sensory nerve terminals, and when activated can evoke cough...
June 29, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28658621/nociceptors-boost-the-resolution-of-fungal-osteoinflammation-via-the-trp-channel-cgrp-jdp2-axis
#15
Kenta Maruyama, Yasunori Takayama, Takeshi Kondo, Ken-Ichi Ishibashi, Bikash Ranjan Sahoo, Hisashi Kanemaru, Yutaro Kumagai, Mikaël M Martino, Hiroki Tanaka, Naohito Ohno, Yoichiro Iwakura, Naoki Takemura, Makoto Tominaga, Shizuo Akira
Candida albicans can enter skeletal tissue through a skin wound in an immunocompromised host or by contamination during orthopedic surgery. Such Candida osteomyelitis is accompanied by severe pain and bone destruction. It is established that nociceptor innervation occurs in skin and bone, but the mechanisms of nociceptive modulation in fungal inflammation remain unclear. In this study, we show that C. albicans stimulates Nav1.8-positive nociceptors via the β-glucan receptor Dectin-1 to induce calcitonin gene-related peptide (CGRP)...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28644897/trpa1-and-trpv1-contribute-to-propofol-mediated-antagonism-of-u46619-induced-constriction-in-murine-coronary-arteries
#16
Pritam Sinharoy, Ian N Bratz, Sayantani Sinha, Loral E Showalter, Spencer R Andrei, Derek S Damron
BACKGROUND: Transient receptor potential (TRP) ion channels have emerged as key components contributing to vasoreactivity. Propofol, an anesthetic is associated with adverse side effects including hypotension and acute pain upon infusion. Our objective was to determine the extent to which TRPA1 and/or TRPV1 ion channels are involved in mediating propofol-induced vasorelaxation of mouse coronary arterioles in vitro and elucidate the potential cellular signal transduction pathway by which this occurs...
2017: PloS One
https://www.readbyqxmd.com/read/28620299/the-alkamide-trans-pellitorine-targets-ppar%C3%AE-via-trpv1-and-trpa1-to-reduce-lipid-accumulation-in-developing-3t3-l1-adipocytes
#17
Barbara Lieder, Mathias Zaunschirm, Ann-Katrin Holik, Jakob P Ley, Joachim Hans, Gerhard E Krammer, Veronika Somoza
Adipose tissue is an important endocrine organ in the human body. However, pathological overgrowth is associated with chronic illness. Regulation of adipogenesis and maturation of adipocytes via bioactive compounds in our daily diet has been in focus of research in the past years and showed promising results for agonists of the ion channels transient receptor potential channel (TRP) V1 and A1. Here, we investigated the anti-adipogenic potential and underlying mechanisms of the alkamide trans-pellitorine present in Piper nigrum via TRPV1 and TRPA1 in 3T3-L1 cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28571526/trpa1-channels-mediate-human-gingival-fibroblast-response-to-phenytoin
#18
M J López-González, E Luis, O Fajardo, V Meseguer, K Gers-Barlag, S Niñerola, F Viana
Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications-the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue...
July 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28530239/thermogenetic-neurostimulation-with-single-cell-resolution
#19
Yulia G Ermakova, Aleksandr A Lanin, Ilya V Fedotov, Matvey Roshchin, Ilya V Kelmanson, Dmitry Kulik, Yulia A Bogdanova, Arina G Shokhina, Dmitry S Bilan, Dmitry B Staroverov, Pavel M Balaban, Andrei B Fedotov, Dmitry A Sidorov-Biryukov, Evgeny S Nikitin, Aleksei M Zheltikov, Vsevolod V Belousov
Thermogenetics is a promising innovative neurostimulation technique, which enables robust activation of neurons using thermosensitive transient receptor potential (TRP) cation channels. Broader application of this approach in neuroscience is, however, hindered by a limited variety of suitable ion channels, and by low spatial and temporal resolution of neuronal activation when TRP channels are activated by ambient temperature variations or chemical agonists. Here, we demonstrate rapid, robust and reproducible repeated activation of snake TRPA1 channels heterologously expressed in non-neuronal cells, mouse neurons and zebrafish neurons in vivo by infrared (IR) laser radiation...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28526851/characterization-of-trpa-channels-in-the-starfish-patiria-pectinifera-involvement-of-thermally-activated-trpa1-in-thermotaxis-in-marine-planktonic-larvae
#20
Shigeru Saito, Gen Hamanaka, Narudo Kawai, Ryohei Furukawa, Jun Gojobori, Makoto Tominaga, Hiroyuki Kaneko, Yoko Satta
The vast majority of marine invertebrates spend their larval period as pelagic plankton and are exposed to various environmental cues. Here we investigated the thermotaxis behaviors of the bipinnaria larvae of the starfish, Patiria pectinifera, in association with TRPA ion channels that serve as thermal receptors in various animal species. Using a newly developed thermotaxis assay system, we observed that P. pectinifera larvae displayed positive thermotaxis toward high temperatures, including toward temperatures high enough to cause death...
May 19, 2017: Scientific Reports
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