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Transient receptor potential

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https://www.readbyqxmd.com/read/29230552/identification-of-clustered-phosphorylation-sites-in-pkd2l1-how-pkd2l1-channel-activation-is-regulated-by-cyclic-adenosine-monophosphate-signaling-pathway
#1
Eunice Yon June Park, Misun Kwak, Kotdaji Ha, Insuk So
Polycystic kidney disease 2-like-1 (PKD2L1), or polycystin-L or TRPP2, formerly TRPP3, is a transient receptor potential (TRP) superfamily member. It is a calcium-permeable non-selective cation channel that regulates intracellular calcium concentration and thereby calcium signaling. PKD2L1 has been reported to take part in hedgehog signaling in renal primary cilia and sour tasting coupling with PKD1L3. In addition to the previous reports, PKD2L1 is recently found to play a crucial role in localization with β2-adrenergic receptor (β2AR) on the neuronal primary cilia...
December 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29227934/gabaa-receptor-activity-modulating-piperine-analogs-in-vitro-metabolic-stability-metabolite-identification-cyp450-reaction-phenotyping-and-protein-binding
#2
Volha Zabela, Timm Hettich, Götz Schlotterbeck, Laurin Wimmer, Marko D Mihovilovic, Fabrice Guillet, Belkacem Bouaita, Bénédicte Shevchenko, Matthias Hamburger, Mouhssin Oufir
In a screening of natural products for allosteric modulators of GABAA receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABAA and TRPV1 activating properties...
December 2, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29226633/characterization-of-membrane-patch-ion-channel-probes-for-scanning-ion-conductance-microscopy
#3
Wenqing Shi, Yuhan Zeng, Cheng Zhu, Yucheng Xiao, Theodore R Cummins, Jianghui Hou, Lane A Baker
Integration of dual-barrel membrane patch-ion channel probes (MP-ICPs) to scanning ion conductance microscopy (SICM) holds promise of providing a revolutionized approach of spatially resolved chemical sensing. A series of experiments are performed to further the understanding of the system and to answer some fundamental questions, in preparation for future developments of this approach. First, MP-ICPs are constructed that contain different types of ion channels including transient receptor potential vanilloid 1 and large conductance Ca2+ -activated K+ channels to establish the generalizability of the methods...
December 11, 2017: Small
https://www.readbyqxmd.com/read/29225078/regulation-of-androgen-receptor-activity-by-transient-interactions-of-its-transactivation-domain-with-general-transcription-regulators
#4
Eva De Mol, Elzbieta Szulc, Claudio Di Sanza, Paula Martínez-Cristóbal, Carlos W Bertoncini, R Bryn Fenwick, Marta Frigolé-Vivas, Marianela Masín, Irene Hunter, Víctor Buzón, Isabelle Brun-Heath, Jesús García, Gianni De Fabritiis, Eva Estébanez-Perpiñá, Iain J McEwan, Ángel R Nebreda, Xavier Salvatella
The androgen receptor is a transcription factor that plays a key role in the development of prostate cancer, and its interactions with general transcription regulators are therefore of potential therapeutic interest. The mechanistic basis of these interactions is poorly understood due to the intrinsically disordered nature of the transactivation domain of the androgen receptor and the generally transient nature of the protein-protein interactions that trigger transcription. Here, we identify a motif of the transactivation domain that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF...
December 6, 2017: Structure
https://www.readbyqxmd.com/read/29222530/seizure-rates-in-enzalutamide-treated-men-with-metastatic-castration-resistant-prostate-cancer-and-risk-of-seizure-the-upward-study
#5
Susan Slovin, William Clark, Joan Carles, Andrew Krivoshik, Jung Wook Park, Fong Wang, Daniel George
Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years without enzalutamide exposure. Objective: To assess seizure incidence in patients with seizure risk factors who were receiving enzalutamide for mCRPC...
December 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29221175/trpm8-is-required-for-survival-and-radioresistance-of-glioblastoma-cells
#6
Dominik Klumpp, Stephanie C Frank, Lukas Klumpp, Efe C Sezgin, Marita Eckert, Lena Edalat, Martin Bastmeyer, Daniel Zips, Peter Ruth, Stephan M Huber
TRPM8 is a Ca2+-permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220863/a-small-dose-of-apomorphine-counteracts-the-deleterious-effects-of-middle-cerebral-artery-occlusion-in-different-models
#7
F Mastroiacovo, A Gaglione, C L Busceti, L Ryskalin, G Bozza, F Nicoletti, F Orzi, F Fornai
The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat...
September 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29217583/structure-of-the-cold-and-menthol-sensing-ion-channel-trpm8
#8
Ying Yin, Mengyu Wu, Lejla Zubcevic, William F Borschel, Gabriel C Lander, Seok-Yong Lee
Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold- and menthol-sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 Å. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29217581/structure-of-the-human-trpm4-ion-channel-in-a-lipid-nanodisc
#9
Henriette E Autzen, Alexander G Myasnikov, Melody G Campbell, Daniel Asarnow, David Julius, Yifan Cheng
Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage dependent manner, but unlike many other TRP channels is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3Å resolution as determined by single particle electron cryo-microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium binding site within the intracellular side of the S1-S4 domain...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29216597/role-of-dopamine-receptors-in-the-anticancer-activity-of-onc201
#10
Christina Leah B Kline, Marie B Ralff, Amriti R Lulla, Jessica M Wagner, Phillip H Abbosh, David T Dicker, Joshua E Allen, Wafik S El-Deiry
ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type-specific manner...
December 4, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29216297/skn-1a-pou2f3-functions-as-a-master-regulator-to-generate-trpm5-expressing-chemosensory-cells-in-mice
#11
Junpei Yamashita, Makoto Ohmoto, Tatsuya Yamaguchi, Ichiro Matsumoto, Junji Hirota
Transient receptor potential channel M5 (Trpm5)-expressing cells, such as sweet, umami, and bitter taste cells in the oropharyngeal epithelium, solitary chemosensory cells in the nasal respiratory epithelium, and tuft cells in the small intestine, that express taste-related genes function as chemosensory cells. Previous studies demonstrated that Skn-1a/Pou2f3, a POU homeodomain transcription factor is expressed in these Trpm5-expressing chemosensory cells, and is necessary for their generation. Trpm5-expressing cells have recently been found in trachea, auditory tube, urethra, thymus, pancreatic duct, stomach, and large intestine...
2017: PloS One
https://www.readbyqxmd.com/read/29215540/the-insulin-receptor-is-colocalized-with-the-trpv1-nociceptive-ion-channel-and-neuropeptides-in-pancreatic-spinal-and-vagal-primary-sensory-neurons
#12
Bence András Lázár, Gábor Jancsó, Orsolya Oszlács, István Nagy, Péter Sántha
OBJECTIVES: Recent observations demonstrated the expression of the insulin receptor (InsR) and its functional interaction with the transient receptor potential vanilloid type 1 receptor (TRPV1) in sensory ganglion neurons. Because sensory nerves are implicated in pancreatic inflammatory processes, we studied the colocalization of the InsR with TRPV1 and proinflammatory neuropeptides in spinal and vagal pancreatic afferent neurons. METHODS: Immunohistochemistry and quantitative morphometry were used to analyze the expression of TRPV1, InsR, substance P (SP), and calcitonin gene-related peptide (CGRP) in retrogradely labeled pancreatic dorsal root ganglion (DRG) and nodose ganglion (NG) neurons...
January 2018: Pancreas
https://www.readbyqxmd.com/read/29215466/sensitivity-of-takifugu-trpa1-to-thermal-stimulations-analyzed-in-oocytes-expression-system
#13
Mai Oda, Yoshihiro Kubo, Osamu Saitoh
Transient receptor potential ankyrin 1 (TRPA1s) from insects and several tetrapod vertebrates except rodents have been reported to be activated by high temperature with a relatively clear threshold. Our previous report, however, indicated that oocytes expressing zebrafish TRPA1b showed cold and heat-induced responses. Further, we also observed that zebrafish TRPA1b was gradually heat activated without a clear threshold. To study the possibility that these unique properties of thermal sensing of zebrafish TRPA1b are common to TRPA1s from other fish, we focused on the thermal response of pufferfish transient receptor potential ankyrin 1 (pfTRPA1) in the present study...
December 5, 2017: Neuroreport
https://www.readbyqxmd.com/read/29214666/low-level-ultrahigh-frequency-and-ultrashort-pulse-blue-laser-irradiation-enhances-osteoblast-extracellular-calcification-by-upregulating-proliferation-and-differentiation-via-transient-receptor-potential-vanilloid-1
#14
Risako Mikami, Koji Mizutani, Akira Aoki, Yukihiko Tamura, Kazuhiro Aoki, Yuichi Izumi
BACKGROUND AND OBJECTIVE: Low-level laser irradiation (LLLI) exerts various biostimulative effects, including promotion of wound healing and bone formation; however, few studies have examined biostimulation using blue lasers. The purpose of this study was to investigate the effects of low-level ultrahigh-frequency (UHF) and ultrashort-pulse (USP) blue laser irradiation on osteoblasts. STUDY DESIGN/ MATERIALS AND METHODS: The MC3T3-E1 osteoblast cell line was used in this study...
December 7, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29214107/diet-and-rosacea-the-role-of-dietary-change-in-the-management-of-rosacea
#15
REVIEW
Emma Weiss, Rajani Katta
Dietary change may play a role in the therapy of rosacea. Certain foods and beverages may act as "triggers" for rosacea exacerbations. These may be divided into heat-related, alcohol-related, capsaicin-related, and cinnamaldehyde-related. One potential pathogenic mechanism may be via the activation of transient receptor potential cation channels, which result in neurogenic vasodilatation. Further research is needed on the role of the gut skin connection in rosacea. Epidemiologic studies suggest that patients with rosacea have a higher prevalence of gastrointestinal disease, and one study reported improvement in rosacea following successful treatment of small intestinal bacterial overgrowth...
October 2017: Dermatology Practical & Conceptual
https://www.readbyqxmd.com/read/29212769/functional-and-structural-characterization-of-a-novel-malignant-hyperthermia-susceptible-variant-of-dhpr-%C3%AE-1a-subunit-cacnb1
#16
Claudio F Perez, Jose M Eltit, Jose R Lopez, Dóra Bodnár, Angela F Dulhunty, Shouvik Aditya, Marco G Casarotto
Malignant Hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3 (SH3)/Guanylate Kinase (GK) core domain of β1a subunit...
December 6, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29211714/structures-of-the-calcium-activated-non-selective-cation-channel-trpm4
#17
Jiangtao Guo, Ji She, Weizhong Zeng, Qingfeng Chen, Youxing Jiang, Xiao-Chen Bai
TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) -modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor potential (TRPM) channels. Here we present the electron cryo-microscopy structures of the mouse TRPM4 channel with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain and inhibits channel activity...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29210126/crosslink-of-calcium-and-sodium-signalling-in-health-and-disease
#18
Alexei Verkhratsky, Mohamed Trebak, Fabiana Perocchi, Daniel Khananishvili, Israel Sekler
Transmembrane ionic gradients, that are indispensable feature of life, are utilised for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca2+ and Na+ is tightly linked through several molecular pathways that generate Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with generation of Na+ and Ca2+ currents. Plasmalemmal Na+ /Ca2+ exchanger by flickering between forward and reverse mode coordinates influx and efflux of both ions with membrane polarisation and cytosolic ion concentration...
December 6, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29209900/effect-of-testosterone-on-trpv1-expression-in-a-model-of-orofacial-myositis-pain-in-the-rat
#19
Xiaofeng Bai, Xia Zhang, Qing Zhou
Recent clinical studies have revealed sex differences in response to transient receptor potential vanilloid 1 (TRPV1) agonist-induced pain. However, the mechanism of these differences in TRPV1-related chronic pain remains unclear. In the present study, we investigate the effects of inflammation and gonadal hormones on TRPV1 expression in trigeminal ganglia. Inflammatory pain was modeled by injecting complete Freund's adjuvant (CFA) into the left masseter muscle in rats. TRPV1 mRNA and protein levels in the trigeminal ganglia of male and female rats following CFA injection were assessed...
December 5, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29209656/ionic-signalling-and-mitochondrial-dynamics
#20
Nada Abuarab, Fangfang Li, Asipu Sivaprasadarao
In age-related diseases, rise in intracellular reactive oxygen species (ROS) causes fragmentation of mitochondrial network. Our recent study demonstrated that ROS activation of TRPM2 (transient receptor potential melastatin-2) channels triggers lysosomal Zn2+ release that, in turn, triggers mitochondrial fragmentation. The findings provide new mechanistic insights that may have therapeutic implications.
2017: Molecular & Cellular Oncology
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