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https://www.readbyqxmd.com/read/28633002/the-trpm2-channel-a-thermo-sensitive-metabolic-sensor
#1
Makiko Kashio, Makoto Tominaga
Living organisms continually experience changes in ambient temperature. In order to detect such temperature changes for adaptive behavioral responses, we evolved the ability to sense temperature. Thermosensitive transient receptor potential (TRP) channels, so-called thermo-TRPs, are involved in many physiological functions in diverse organisms and constitute important temperature sensors. One of the important roles of thermo-TRPs is detecting ambient temperature in sensory neurons. Importantly, the functional expression of thermo-TRPs is observed not only in sensory neurons but also in tissues and cells that are not exposed to drastic temperature changes, indicating that thermo-TRPs are involved in many physiological functions within the body's normal temperature range...
June 20, 2017: Channels
https://www.readbyqxmd.com/read/28620309/inhibition-of-the-trpm2-and-trpv1-channels-through-hypericum-perforatum-in-sciatic-nerve-injury-induced-rats-demonstrates-their-key-role-in-apoptosis-and-mitochondrial-oxidative-stress-of-sciatic-nerve-and-dorsal-root-ganglion
#2
Fuat Uslusoy, Mustafa Nazıroğlu, Bilal Çiğ
Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca(2+) entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28603015/activation-of-a-ca-2-dependent-cation-conductance-with-properties-of-trpm2-by-reactive-oxygen-species-in-lens-epithelial-cells
#3
Susanne Keckeis, Laura Wernecke, Daniel J Salchow, Nadine Reichhart, Olaf Strauß
Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca(2+)-dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca(2+)- and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca(2+)-activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells...
June 8, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28589630/synthesis-of-a-bioreversible-masked-lipophilic-adenosine-diphosphate-ribose-derivative
#4
Chris Meier, Katharina Pahnke
The design of a bioreversible protected, lipophilic sugar nucleotide as a potential membrane-permeable precursor of adenosine diphosphate ribose (ADPR) is described. ADPR is the most potent activator of the TRPM2 ion channel. Membrane permeable, lipophilic derivatives of ADPR are of great interest as tools to study the mechanism of TRPM2. The approach described herein was based on our recently disclosed 'DiPPro' and 'TriPPPro'-prodrug approaches developed for the intracellular delivery of nucleotides. A lipophilic, bioreversible masked ADPR-analog was prepared in high yields containing an enzymatically cleavable 4-pentanoyloxybenzyl (PB)-mask at the phosphate moiety next to the 5'-position of adenosine as well as O-acetyl groups...
June 6, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28588083/science-signaling-podcast-for-6-june-2017-calcium-signaling-and-dry-mouth
#5
Indu Ambudkar, Annalisa M VanHook
This Podcast features a conversation with Indu Ambudkar, senior author of a Research Resource that appears in the 6 June 2017 issue of Science Signaling, about how activation of the cation channel TRPM2 is involved in radiation-induced dry mouth. Patients who receive radiation therapy for head and neck cancers often develop dry mouth as a side effect, and this condition is frequently permanent. Radiation does not kill cells in the salivary gland, yet it causes the acinar cells of the gland to reduce the amount of saliva they secrete...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28588080/radiation-inhibits-salivary-gland-function-by-promoting-stim1-cleavage-by-caspase-3-and-loss-of-soce-through-a-trpm2-dependent-pathway
#6
Xibao Liu, Baijuan Gong, Lorena Brito de Souza, Hwei Ling Ong, Krishna P Subedi, Kwong Tai Cheng, William Swaim, Changyu Zheng, Yasuo Mori, Indu S Ambudkar
Store-operated Ca(2+) entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2(+/+) , but not those from TRPM2(-/-) mice, displayed an increase in the concentrations of mitochondrial Ca(2+) and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28569571/curcumin-inhibits-oxidative-stress-induced-trpm2-channel-activation-calcium-ion-entry-and-apoptosis-values-in-sh-sy5y-neuroblastoma-cells-involvement-of-transfection-procedure
#7
Ahmi Öz, Ömer Çelik
Transient Receptor Potential (TRP) channels are mostly Ca(2+) permeable cation channels. Transient Receptor Potential Melastatin-like 2 (TRPM2) is expressed in neurological tissues such as brain, dorsal root ganglia (DRG) neurons, hippocampus and also liver, heart and kidney. The SH-SY5Y cells are mostly used as a cellular model of neurodegenerative diseases, Alzheimer's and Parkinson's diseases. Curcumin, shows phenolic structure, synthesized by Curcuma longa L. (turmeric), has powerful non-enzymatically antioxidant effects compared with Vitamin E...
June 1, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/28532624/tyrphostin-ag-related-compounds-attenuate-h2o2-induced-trpm2-dependent-and-independent-cellular-responses
#8
Shinichiro Yamamoto, Takahiro Toda, Ryo Yonezawa, Takaharu Negoro, Shunichi Shimizu
PURPOSE: TRPM2 is a Ca(2+)-permeable channel that is activated by H2O2. TRPM2-mediated Ca(2+) signaling has been implicated in the aggravation of inflammatory diseases. Therefore, the development of TRPM2 inhibitors to prevent the aggravation of these diseases is expected. We recently reported that some Tyrphostin AG-related compounds inhibited the H2O2-induced activation of TRPM2 by scavenging the intracellular hydroxyl radical. In the present study, we examined the effects of AG-related compounds on H2O2-induced cellular responses in human monocytic U937 cells, which functionally express TRPM2...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#9
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28515263/ligand-induced-activation-of-human-trpm2-requires-the-terminal-ribose-of-adpr-and-involves-arg1433-and-tyr1349
#10
Ralf Fliegert, Joanna M Watt, Anja Schöbel, Monika D Rozewitz, Christelle Moreau, Tanja Kirchberger, Mark P Thomas, Wiebke Sick, Andrea C Araujo, Angelika Harneit, Barry V L Potter, Andreas H Guse
TRPM2 (transient receptor potential channel, subfamily melastatin, member 2) is a Ca(2+)-permeable non-selective cation channel activated by the binding of adenosine 5'-diphosphoribose (ADPR) to its cytoplasmic NUDT9H domain (NUDT9 homology domain). Activation of TRPM2 by ADPR downstream of oxidative stress has been implicated in the pathogenesis of many human diseases, rendering TRPM2 an attractive novel target for pharmacological intervention. However, the structural basis underlying this activation is largely unknown...
June 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28499580/transient-receptor-potential-trp-channels-as-molecular-targets-in-lung-toxicology-and-associated-diseases
#11
REVIEW
Alexander Dietrich, Dirk Steinritz, Thomas Gudermann
The lungs as the gateways of our body to the external environment are essential for gas exchange. They are also exposed to toxicants from two sides, the airways and the vasculature. Apart from naturally produced toxic agents, millions of human made chemicals were produced since the beginning of the industrial revolution whose toxicity still needs to be determined. While the knowledge about toxic substances is increasing only slowly, a paradigm shift regarding the proposed mechanisms of toxicity at the plasma membrane emerged...
April 26, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28464448/gene-expression-changes-of-thermo-sensitive-transient-receptor-potential-channels-in-obese-mice
#12
Wuping Sun, Chen Lib, Yonghong Zhang, Changyu Jiang, Mingzhu Zhai, Qian Zhou, Lizu Xiao, Qiwen Deng
Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) sharethe similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using Reverse Transcriptase-quantitative PCRs (RT-qPCR)...
May 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28461775/dust-particles-induced-intracellular-ca-2-signaling-and-reactive-oxygen-species-in-lung-fibroblast-cell-line-mrc5
#13
Dong Un Lee, Min Jeong Ji, Jung Yun Kang, Sun Young Kyung, Jeong Hee Hong
Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established Ca(2+) signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular Ca(2+) signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular Ca(2+) signaling in human lung fibroblasts MRC5 cells...
May 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#14
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28363841/aca-an-inhibitor-phospholipases-a2-and-transient-receptor-potential-melastatin-2-channels-attenuates-okadaic-acid-induced-neurodegeneration-in-rats
#15
Murat Cakir, Halil Duzova, Suat Tekin, Elif Taslıdere, Gul Busra Kaya, Yılmaz Cigremis, Tuba Ozgocer, Saim Yologlu
AIM: In recent studies, it has been shown that the Transient Receptor Potential Melastatin-2 Channels (TRPM2) and Phospholipases A2 (PLA2) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA2 inhibitor N-(p-amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA). MAIN METHODS: OKA (200ng/10μl) was administered bilateral intracerebroventricularly as a single injection...
May 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28349092/the-trpm2-channel-in-temperature-detection-and-thermoregulation
#16
COMMENT
Gretel B Kamm, Jan Siemens
No abstract text is available yet for this article.
2017: Temperature: Multidisciplinary Biomedical Journal
https://www.readbyqxmd.com/read/28332277/sequencing-of-sporadic-attention-deficit-hyperactivity-disorder-adhd-identifies-novel-and-potentially-pathogenic-de-novo-variants-and-excludes-overlap-with-genes-associated-with-autism-spectrum-disorder
#17
Daniel Seung Kim, Amber A Burt, Jane E Ranchalis, Beth Wilmot, Joshua D Smith, Karynne E Patterson, Bradley P Coe, Yatong K Li, Michael J Bamshad, Molly Nikolas, Evan E Eichler, James M Swanson, Joel T Nigg, Deborah A Nickerson, Gail P Jarvik
Attention-Deficit Hyperactivity Disorder (ADHD) has high heritability; however, studies of common variation account for <5% of ADHD variance. Using data from affected participants without a family history of ADHD, we sought to identify de novo variants that could account for sporadic ADHD. Considering a total of 128 families, two analyses were conducted in parallel: first, in 11 unaffected parent/affected proband trios (or quads with the addition of an unaffected sibling) we completed exome sequencing. Six de novo missense variants at highly conserved bases were identified and validated from four of the 11 families: the brain-expressed genes TBC1D9, DAGLA, QARS, CSMD2, TRPM2, and WDR83...
June 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#18
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Ying Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters, but understanding of these channels remains inadequate. Here we focus on transient receptor potential canonical 4 and 5 proteins (TRPC4 and TRPC5), which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested, including in epilepsy, innate fear, pain, and cardiac remodeling, but limitations in tools to probe these channels have restricted progress...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28322340/signalling-mechanisms-mediating-zn-2-induced-trpm2-channel-activation-and-cell-death-in-microglial-cells
#19
Sharifah Syed Mortadza, Joan A Sim, Martin Stacey, Lin-Hua Jiang
Excessive Zn(2+) causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H2O2/Zn(2+)-induced Ca(2+) signalling and cell death in microglial cells. H2O2/Zn(2+) induced concentration-dependent increases in cytosolic Ca(2+) concentration ([Ca(2+)]c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H2O2/Zn(2+) induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293191/an-exploration-of-charge-compensating-ion-channels-across-the-phagocytic-vacuole-of-neutrophils
#20
Juliet R Foote, Philippe Behe, Mathew Frampton, Adam P Levine, Anthony W Segal
Neutrophils phagocytosing bacteria and fungi exhibit a burst of non-mitochondrial respiration that is required to kill and digest the engulfed microbes. This respiration is accomplished by the movement of electrons across the wall of the phagocytic vacuole by the neutrophil NADPH oxidase, NOX2. In this study, we have attempted to identify the non-proton ion channels or transporters involved in charge compensation by examining the effect of inhibitors on vacuolar pH and cross-sectional area, and on oxygen consumption...
2017: Frontiers in Pharmacology
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