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TRPM2

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https://www.readbyqxmd.com/read/28532624/tyrphostin-ag-related-compounds-attenuate-h2o2-induced-trpm2-dependent-and-independent-cellular-responses
#1
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 6, 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
#2
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-arg-1433-and-tyr-1349
#3
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 Vl Potter, Andreas H Guse
TRPM2 is a Ca(2+)-permeable non-selective cation channel activated by binding of adenosine 5'-diphosphoribose (ADPR) to its cytoplasmic NUDT9H domain. Activation of TRPM2 by ADPR downstream of oxidative stress has been implicated in the pathogenesis of a number of human diseases rendering TRPM2 an attractive novel target for pharmacological intervention. However, the structural basis underlying this activation is largely unknown. Since ADP alone did not activate or antagonize the channel, we used a chemical biology approach employing synthetic analogues to focus on the role of the ADPR terminal ribose...
May 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28499580/transient-receptor-potential-trp-channels-as-molecular-targets-in-lung-toxicology-and-associated-diseases
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
March 22, 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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28292196/nitration-of-trpm2-as-a-molecular-switch-induces-autophagy-during-brain-pericyte-injury
#14
Quan Jiang, Yinping Gao, Chengkun Wang, Rongrong Tao, Yan Wu, Kaiyu Zhan, Meihua Liao, Nannan Lu, Yingmei Lu, Christopher S Wilcox, Jianhong Luo, Lin-Hua Jiang, Wei Yang, Feng Han
AIMS: Dysfunction of neurovascular pericytes underlies breakdown of the blood-brain barrier, but the molecular mechanisms are largely unknown. In this study, we evaluated the role of the transient receptor potential melastatin-related 2 (TRPM2) channel and autophagy during brain pericyte injury both in vitro and in vivo. RESULTS: A rapid induction in autophagy in human brain vascular pericytes, in the zinc oxide nanoparticles (ZnO-NP)-induced cell stress model, was paralleled with an increase in the expression of the TRPM2-S truncated isoform, which was abolished by treatment with a nitric oxide synthase inhibitor and a peroxynitrite scavenger...
April 18, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28223219/trpm2-contributes-to-lpc-induced-intracellular-ca-2-influx-and-microglial-activation
#15
Heejin Jeong, Yong Ho Kim, Yunsin Lee, Sung Jun Jung, Seog Bae Oh
Microglia are the resident immune cells which become activated in some pathological conditions in central nervous system (CNS). Lysophosphatidylcholine (LPC), an endogenous inflammatory phospholipid, is implicated in immunomodulatory function of glial cells in the CNS. Although several studies uncovered that LPC induces intracellular Ca(2+) influx and morphologic change in microglia, there is still no direct evidence showing change of phosphorylation of mitogen-activated protein kinase (MAPK) p38 (p-p38), a widely used microglia activation marker, by LPC...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28199210/trpm2-a-potential-drug-target-to-retard-oxidative-stress
#16
Jun Li, Yunling Gao, Xianying Bao, Fengna Li, Wei Yao, Zemeng Feng, Yulong Yin
The Transient Receptor Potential Melastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel and Adenosine 5'-DiphosPhatase Ribose (ADPR) hydrolase function. TRPM2 is involved in Ca(2+) signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca(2+) entry and Ca(2+)-dependent cellular reactions such as endothelial hyper-permeability and apoptosis...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28108595/identification-of-the-adpr-binding-pocket-in-the-nudt9-homology-domain-of-trpm2
#17
Peilin Yu, Xiwen Xue, Jianmin Zhang, Xupang Hu, Yan Wu, Lin-Hua Jiang, Hongwei Jin, Jianhong Luo, Liangren Zhang, Zhenming Liu, Wei Yang
Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown...
February 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28101241/potential-role-of-melastatin-related-transient-receptor-potential-cation-channel-subfamily-m-gene-expression-in-the-pathogenesis-of-urinary-bladder-cancer
#18
Gülay Güleç Ceylan, Ebru Etem Önalan, Tuncay Kuloğlu, Gülten Aydoğ, İbrahim Keleş, Şenol Tonyali, Cavit Ceylan
Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28097492/activation-of-trpm2-and-trpv1-channels-in-dorsal-root-ganglion-by-nadph-oxidase-and-protein-kinase-c-molecular-pathways-a-patch-clamp-study
#19
Mustafa Nazıroğlu
Despite considerable research, the mechanisms of neuropathic pain induced by excessive oxidative stress production and overload calcium ion (Ca(2+)) entry in dorsal root ganglion (DRG) remain substantially unidentified. The transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) channels are activated with different stimuli including oxidative stress. TRPM2 and TRPV1 have been shown to be involved in induction of neuropathic pain. However, the activation mechanisms of TRPM2 and TRPV1 via NADPH oxidase and protein kinase C (PKC) pathways are poorly understood...
January 17, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28028935/renoprotection-focus-on-trpv1-trpv4-trpc6-and-trpm2
#20
REVIEW
L Markó, M Mannaa, T N Haschler, S Krämer, M Gollasch
Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca(2+) influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS)...
March 2017: Acta Physiologica
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