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https://www.readbyqxmd.com/read/29689522/differential-effects-of-lipopolysaccharide-on-mouse-sensory-trp-channels
#1
Brett Boonen, Yeranddy A Alpizar, Alicia Sanchez, Alejandro López-Requena, Thomas Voets, Karel Talavera
Acute neurogenic inflammation and pain associated to bacterial infection have been traditionally ascribed to sensitization and activation of sensory nerve afferents secondary to immune cell stimulation. However, we recently showed that lipopolysaccharides (LPS) directly activate the Transient Receptor Potential channels TRPA1 in sensory neurons and TRPV4 in airway epithelial cells. Here we investigated whether LPS activates other sensory TRP channels expressed in sensory neurons. Using intracellular Ca2+ imaging and patch-clamp we determined the effects of LPS on recombinant TRPV1, TRPV2, TRPM3 and TRPM8, heterologously expressed in HEK293T cells...
April 14, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29604058/mutations-in-the-voltage-sensing-domain-affect-the-alternative-ion-permeation-pathway-in-the-trpm3-channel
#2
Katharina Held, Fabian Gruss, Vincenzo Davide Aloi, Annelies Janssens, Chris Ulens, Thomas Voets, Joris Vriens
Transient receptor potential (TRP) channels are cationic channels involved in a broad array of functions, including homeostasis, motility and sensory functions. TRP channel subunits consist of six transmembrane segments (S1-S6), and form tetrameric channels with a central pore formed by the region encompassing S5 and S6. Recently, evidence was provided for the existence of an alternative ion permeation pathway in TRPM3, which allows large inward currents upon hyperpolarization independently from the central pore...
March 31, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29539642/a-trp-channel-trio-mediates-acute-noxious-heat-sensing
#3
Ine Vandewauw, Katrien De Clercq, Marie Mulier, Katharina Held, Silvia Pinto, Nele Van Ranst, Andrei Segal, Thierry Voet, Rudi Vennekens, Katharina Zimmermann, Joris Vriens, Thomas Voets
Acute pain represents a crucial alarm signal to protect us from injury. Whereas the nociceptive neurons that convey pain signals were described more than a century ago, the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified. Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional...
March 29, 2018: Nature
https://www.readbyqxmd.com/read/29382303/genetic-variation-of-the-gene-coding-for-microrna-204-mir-204-is-a-risk-factor-in-acute-myeloid-leukaemia
#4
Aleksandra Butrym, Piotr Łacina, Kazimierz Kuliczkowski, Katarzyna Bogunia-Kubik, Grzegorz Mazur
BACKGROUND: MicroRNAs (miRNAs or miRs) are small molecules known to be involved in post-transcriptional gene expression. Many of them have been shown to influence risk for various diseases. Recent studies suggest that lower expression of miR-204, a gene coding for miRNA-204, is correlated with shorter survival in patients with acute myeloid leukaemia (AML). This observation prompted us to analyse the effect of two polymorphisms of the miR-204 gene, one in the upstream flanking region (rs718447 A > G) and the other inside the gene itself (rs112062096 A > G), both also in intron 3 of the TRPM3 gene...
January 30, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29368357/puerarin-inhibits-trpm3-mir-204-to-promote-mc3t3-e1-cells-proliferation-differentiation-and-mineralization
#5
Xiangwei Zeng, Qian Feng, Fengming Zhao, Chao Sun, Tao Zhou, Jing Yang, Xiuqin Zhan
Puerarin is an isoflavonoid phytoestrogen extracted from the root of Radix Pueraria, has attracted increasing attention because of its beneficial effects on anti-osteoporosis, but the molecular mechanisms underlying its actions on osteoblasts are not fully understood. The current study aimed to investigate the effect of puerarin on MC3T3-E1 osteoblastic cells proliferation, differentiation and mineralization, in vitro and its underlying mechanisms. The results indicated that puerarin significantly promoted the osteoblasts proliferation, enhanced alkaline phosphatase activity and increased the formation of mineralized nodules...
January 24, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29305649/sensing-the-heat-with-trpm3
#6
REVIEW
Joris Vriens, Thomas Voets
Heat sensation, the ability to detect warm and noxious temperatures, is an ancient and indispensable sensory process. Noxious temperatures can have detrimental effects on the physiology and integrity of cells, and therefore, the detection of environmental hot temperatures is absolutely crucial for survival. Temperature-sensitive ion channels, which conduct ions in a highly temperature-dependent manner, have been put forward as molecular thermometers expressed at the endings of sensory neurons. In particular, several temperature-sensitive members of the transient receptor potential (TRP) superfamily of ion channels have been identified, and a multitude of in vivo studies have shown that the capsaicin-sensitive TRPV1 channel plays a key role as a noxious heat sensor...
January 5, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29305012/regulation-of-gene-transcription-following-stimulation-of-transient-receptor-potential-trp-channels
#7
Gerald Thiel, Andrea Lesch, Sandra Rubil, Tobias M Backes, Oliver G Rössler
Transient receptor potential (TRP) channels belong to a heterogeneous superfamily of cation channels that are involved in the regulation of numerous biological functions, including regulation of Ca2+ and glucose homeostasis, tumorigenesis, temperature, and pain sensation. To understand the functions of TRP channels, their associated intracellular signaling pathways and molecular targets have to be identified on the cellular level. Stimulation of TRP channels frequently induces an influx of Ca2+ ions into the cells and the subsequent activation of protein kinases...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29282613/regulation-of-pain-and-itch-by-trp-channels
#8
REVIEW
Carlene Moore, Rupali Gupta, Sven-Eric Jordt, Yong Chen, Wolfgang B Liedtke
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur...
February 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28982580/stimulation-of-transient-receptor-potential-m3-trpm3-channels-increases-interleukin-8-gene-promoter-activity-involving-ap-1-and-extracellular-signal-regulated-protein-kinase
#9
Sandra Rubil, Andrea Lesch, Naofumi Mukaida, Gerald Thiel
Stimulation of Ca2+ permeable TRPM3 (transient receptor potential melastatin-3) channels with the steroid ligand pregnenolone sulfate activates stimulus-responsive transcription factors, including the transcription factor AP-1 (activator protein-1). As part of a search for AP-1-regulated target genes we analyzed the gene encoding interleukin-8 (IL-8) in HEK293 cells expressing TRPM3 channels. Here, we show that stimulation of TRPM3 channels activated transcription of an IL-8 promoter-controlled reporter gene that was embedded into the chromatin of the cells...
March 2018: Cytokine
https://www.readbyqxmd.com/read/28947970/circular-rnas-promote-trpm3-expression-by-inhibiting-hsa-mir-130a-3p-in-coronary-artery-disease-patients
#10
Ren-You Pan, Ping Liu, Hai-Tang Zhou, Wei-Xin Sun, Jun Song, Jiang Shu, Guo-Jing Cui, Zhi-Jian Yang, En-Zhi Jia
We investigated the differential expression of circular RNAs (circRNAs) in plasma samples from three coronary artery disease (CAD) patients to identify putative therapeutic targets. We identified 24 differentially expressed circRNAs (18 up-regulated and 6 down-regulated) and 7 differentially expressed mRNAs (6 up-regulated and 1 down-regulated) in CAD patients based on competing endogenous RNA (ceRNA) microarray analysis. MiR-221(p = 0.001), miR-155(p = 0.049), and miR-130a (p = 0.001) were downregulated in CAD patients based on qRT-PCR analysis of another independent population of 932 study subjects (648 CAD subjects and 284 controls)...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28924972/targeting-nociceptive-trp-channels-to-treat-chronic-pain-current-state-of-the-field
#11
REVIEW
Magdalene M Moran, Arpad Szallasi
Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of Transient Receptor Potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically...
September 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28891794/a-new-target-for-g-protein-signaling
#12
László Csanády
G protein-coupled receptor stimulation inhibits TRPM3 channel activity through direct binding of the Gβγ subunit to the channel.
September 11, 2017: ELife
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#13
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28829742/inhibition-of-transient-receptor-potential-melastatin-3-ion-channels-by-g-protein-%C3%AE-%C3%AE-subunits
#14
Doreen Badheka, Yevgen Yudin, Istvan Borbiro, Cassandra M Hartle, Aysenur Yazici, Tooraj Mirshahi, Tibor Rohacs
Transient receptor potential melastatin 3 (TRPM3) channels are activated by heat, and chemical ligands such as pregnenolone sulphate (PregS) and CIM0216. Here, we show that activation of receptors coupled to heterotrimeric Gi/o proteins inhibits TRPM3 channels. This inhibition was alleviated by co-expression of proteins that bind the βγ subunits of heterotrimeric G-proteins (Gβγ). Co-expression of Gβγ, but not constitutively active Gαi or Gαo, inhibited TRPM3 currents. TRPM3 co-immunoprecipitated with Gβ, and purified Gβγ proteins applied to excised inside-out patches inhibited TRPM3 currents, indicating a direct effect...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28826490/g-protein-%C3%AE-%C3%AE-subunits-inhibit-trpm3-ion-channels-in-sensory-neurons
#15
Talisia Quallo, Omar Alkhatib, Clive Gentry, David A Andersson, Stuart Bevan
Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM3 expressed in mouse dorsal root ganglion (DRG) neurons is inhibited by agonists of the Gi-coupled µ opioid, GABA-B and NPY receptors. These agonist effects are mediated by direct inhibition of TRPM3 by Gβγ subunits, rather than by a canonical cAMP mediated mechanism...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28826482/anti-nociceptive-action-of-peripheral-mu-opioid-receptors-by-g-beta-gamma-protein-mediated-inhibition-of-trpm3-channels
#16
Sandeep Dembla, Marc Behrendt, Florian Mohr, Christian Goecke, Julia Sondermann, Franziska M Schneider, Marlene Schmidt, Julia Stab, Raissa Enzeroth, Michael G Leitner, Paulina Nuñez-Badinez, Jochen Schwenk, Bernd Nürnberg, Alejandro Cohen, Stephan E Philipp, Wolfgang Greffrath, Moritz Bünemann, Dominik Oliver, Eleonora Zakharian, Manuela Schmidt, Johannes Oberwinkler
Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful analgesia. The cellular mechanisms downstream of peripheral µORs are not well understood. Here, we show in neurons of murine dorsal root ganglia that pro-nociceptive TRPM3 channels, present in the peripheral parts of nociceptors, are strongly inhibited by µOR activation, much more than other TRP channels in the same compartment, like TRPV1 and TRPA1...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#17
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/28720517/transient-receptor-potential-trpm3-channels-pharmacology-signaling-and-biological-functions
#18
REVIEW
Gerald Thiel, Sandra Rubil, Andrea Lesch, Lisbeth A Guethlein, Oliver G Rössler
The transient receptor potential melastatin-3 (TRPM3) channel belongs to the family of transient receptor potential (TRP) cation channels that are expressed in a variety of tissues and cell types, including dorsal root ganglia, cardiomyocytes and pancreatic beta-cells. Although its natural ligands are currently unknown, TRPM3 channels can be activated by the neurosteroid pregnenolone sulfate, the synthetic ligand CIM0216, and by noxious heat. TRPM3 channels are regulated by phosphoinositides, and perhaps by calmodulin...
July 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28549093/autoantibodies-in-melanoma-associated-retinopathy-recognize-an-epitope-conserved-between-trpm1-and-trpm3
#19
Robert M Duvoisin, Tammie L Haley, Gaoying Ren, Iwona Strycharska-Orczyk, James P Bonaparte, Catherine W Morgans
Purpose: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with malignant melanoma and the presence of anti-retinal autoantibodies, including autoantibodies against transient receptor potential melanopsin 1 (TRPM1), a cation channel expressed by both melanocytes and retinal bipolar cells. The goal of this study was to further map the antigenic epitope. Methods: Patient sera were tested by immunofluorescence and Western blotting on HEK293 cells transfected with enhanced green fluorescent protein (EGFP)-TRPM1 fusion constructs and mouse retina sections...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28388577/il-6r-stat3-mir-204-feedback-loop-contributes-to-cisplatin-resistance-of-epithelial-ovarian-cancer-cells
#20
Xiaolan Zhu, Huiling Shen, Xinming Yin, Lulu Long, Xiaofang Chen, Fan Feng, Yueqin Liu, Peiqing Zhao, Yue Xu, Mei Li, Wenlin Xu, Yuefeng Li
Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target...
June 13, 2017: Oncotarget
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