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TRPM2

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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
#1
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
#2
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin 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...
March 21, 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
#3
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
#4
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
#5
Quan Jiang, Yinping Gao, Chengkun Wang, Rong-Rong Tao, Yan Wu, Kaiyu Zhan, Mei-Hua Liao, Nannan Lu, Ying-Mei Lu, Christopher Stuart 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 TRPM2 channel and autophagy during brain pericyte injury in vitro and in vivo. RESULTS: A rapid induction in autophagy in human brain vascular pericytes, in 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 peroxynitrite scavenger...
March 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28223219/trpm2-contributes-to-lpc-induced-intracellular-ca-2-influx-and-microglial-activation
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28028077/endogenous-%C3%AE-2a-adrenoceptor-operated-sympathoadrenergic-tones-attenuate-insulin-secretion-via-camp-trpm2-signaling
#12
Kiyonori Ito, Katsuya Dezaki, Masashi Yoshida, Hodaka Yamada, Rina Miura, Rauza Sukma Rita, Susumu Ookawara, Kaoru Tabei, Masanobu Kawakami, Kazuo Hara, Yoshiyuki Morishita, Toshihiko Yada, Masafumi Kakei
In pancreatic β-cells, pharmacological concentrations of catecholamines, including adrenaline, have been used to inhibit insulin release and explore the multiple mechanisms involved. However, the significance of these signaling pathways for physiological adrenergic functions in β-cells is largely unknown. In the process of glucose-induced insulin secretion, opening of background current through non-selective cation channels (NSCCs) might facilitate membrane depolarization by closure of the ATP-sensitive K(+) channels...
December 27, 2016: Diabetes
https://www.readbyqxmd.com/read/28008929/the-overexpressed-functional-transient-receptor-potential-channel-trpm2-in-oral-squamous-cell-carcinoma
#13
Ling-Yan Zhao, Wan-Lin Xu, Zeng-Qi Xu, Cui Qi, Yang Li, Jie Cheng, Lai-Kui Liu, Yu-Nong Wu, Jun Gao, Jin-Hai Ye
TRPM2, one member of the transient receptor potential (TRP) protein super-family, is a Ca(2+)-permeable channel that is activated by oxidative stress and confers susceptibility to cell death. In the human tongue specimens of carcinoma and the tongue carcinoma SCC cell lines, we observed the enhanced expression of TRPM2. By means of the whole-cell electrophysiological recording, the ADPR-induced currents mediated by TRPM2 were recorded in cultured SCC9 cells. Moreover, after H2O2 treatment for 24 hours, the apoptotic number of SCC9 cells was significantly increased...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28007458/oxidative-stress-activates-the-trpm2-ca-2-camkii-ros-signaling-loop-to-induce-cell-death-in-cancer-cells
#14
Qian Wang, Lihong Huang, Jianbo Yue
High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca(2+)-permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca(2+) influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca(2+)-CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells...
December 19, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27957685/trpm2-promotes-neurotoxin-mpp-mptp-induced-cell-death
#15
Yuyang Sun, Pramod Sukumaran, Senthil Selvaraj, Nicholas I Cilz, Anne Schaar, Saobo Lei, Brij B Singh
In neurons, Ca(2+) is essential for a variety of physiological processes that regulate gene transcription to neuronal growth and their survival. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ions (MPP(+)) are potent neurotoxins that selectively destroys the dopaminergic (DA) neurons and mimics Parkinson's disease (PD) like symptoms, but the mechanism as how MPP(+)/MPTP effects DA neuron survival is not well-understood. In the present study, we found that MPP(+) treatment increased the level of reactive oxygen species (ROS) that activates and upregulates the expression and function of melastatin-like transient receptor potential (TRPM) subfamily member, melastatin-like transient receptor potential channel 2 (TRPM2)...
December 12, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27919223/trpm2-snp-genotype-previously-associated-with-susceptibility-to-rhodococcus-equi-pneumonia-in-quarter-horse-foals-displays-differential-gene-expression-identified-using-rna-seq
#16
Cole M McQueen, Canaan M Whitfield-Cargile, Kranti Konganti, Glenn P Blodgett, Scott V Dindot, Noah D Cohen
BACKGROUND: Rhodococcus equi (R. equi) is an intracellular bacterium that affects young foals and immuno-compromised individuals causing severe pneumonia. Currently, the genetic mechanisms that confer susceptibility and/or resistance to R. equi are not fully understood. Previously, using a SNP-based genome-wide association study, we identified a region on equine chromosome 26 associated with culture-confirmed clinical pneumonia. To better characterize this region and understand the function of the SNP located within TRPM2 that was associated with R...
December 5, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27872485/the-neuroprotective-action-of-dexmedetomidine-on-apoptosis-calcium-entry-and-oxidative-stress-in-cerebral-ischemia-induced-rats-contribution-of-trpm2-and-trpv1-channels
#17
Hatice Akpınar, Mustafa Nazıroğlu, İshak Suat Övey, Bilal Çiğ, Orhan Akpınar
Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG neurons. Fifty-six rats were divided into five groups. A placebo was given to control, sham control, and ISC groups, respectively. In the third group, ISC was induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 μg/kg) 3, 24, and 48 hours after ISC induction...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27868415/-association-of-single-nucleotide-polymorphism-in-exon-of-transient-receptor-potential-melastatin-2-gene-with-sepsis
#18
Minbo Fang, Qixing Chen, Shuijing Wu, Xiangming Fang
Objective: To investigate the association between single nucleotide polymorphism (SNP) in the 11th exon of transient receptor potential melastatin 2 (TRPM2) gene with the susceptibility and outcome of sepsis. Methods: A total of 119 septic patients and 112 normal subjects were enrolled from the First Affiliated Hospital, Zhejiang University School of Medicine. Among 119 septic patients, 62 died (fatal group) and 57 survived (survival group) within 28 days of disease onset. The genotypes of these individuals were detected using TaqMan allelic discrimination assays, and its correlations with susceptibility and outcome of sepsis were analyzed...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27832523/ovariectomy-induced-mitochondrial-oxidative-stress-apoptosis-and-calcium-ion-influx-through-trpa1-trpm2-and-trpv1-are-prevented-by-17%C3%AE-estradiol-tamoxifen-and-raloxifene-in-the-hippocampus-and-dorsal-root-ganglion-of-rats
#19
Yener Yazğan, Mustafa Nazıroğlu
Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca(2+) influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca(2+) influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats...
November 10, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27792045/transient-receptor-potential-melastatin-2-regulates-phagosome-maturation-and-is-required-for-bacterial-clearance-in-escherichia-coli-sepsis
#20
ZhanQin Zhang, Ping Cui, Kai Zhang, QiXing Chen, XiangMing Fang
BACKGROUND: Transient receptor potential melastatin 2 is a Ca-permeable cation channel abundantly expressed in macrophages. Trpm2 mice showed exacerbated infection and mortality during polymicrobial sepsis, which is associated with inefficient bacterial killing in macrophages. However, the mechanism of transient receptor potential melastatin 2 regulating bacterial killing remains unknown. METHODS: Trpm2 mice were intraperitoneally injected with Escherichia coli...
January 2017: Anesthesiology
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