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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
#1
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
#2
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
#3
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
#4
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...
October 28, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27777418/the-phf21b-gene-is-associated-with-major-depression-and-modulates-the-stress-response
#5
M-L Wong, M Arcos-Burgos, S Liu, J I Vélez, C Yu, B T Baune, M C Jawahar, V Arolt, U Dannlowski, A Chuah, G A Huttley, R Fogarty, M D Lewis, S R Bornstein, J Licinio
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD)...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27771354/paradoxical-lower-sensitivity-of-locus-coeruleus-than-substantia-nigra-pars-compacta-neurons-to-acute-actions-of-rotenone
#6
Andrew G Yee, Peter S Freestone, Ji-Zhong Bai, Janusz Lipski
Parkinson's disease (PD) is not only associated with degeneration of dopaminergic (DAergic) neurons in the Substantia Nigra, but also with profound loss of noradrenergic neurons in the Locus Coeruleus (LC). Remarkably, LC degeneration may exceed, or even precede the loss of nigral DAergic neurons, suggesting that LC neurons may be more susceptible to damage by various insults. Using a combination of electrophysiology, fluorescence imaging and electrochemistry, we directly compared the responses of LC, nigral DAergic and nigral non-dopaminergic (non-DAergic) neurons in rat brain slices to acute application of rotenone, a mitochondrial toxin used to create animal and in vitro models of PD...
October 19, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27767094/warm-feelings-for-trpm2
#7
Thomas Voets
Two recent studies reveal a crucial role for the cation channel TRPM2 in sensing warm temperatures, both in the thermoregulatory center of the brain and in the somatosensory system.
October 21, 2016: Cell Research
https://www.readbyqxmd.com/read/27731349/trpm2-regulates-txnip-mediated-nlrp3-inflammasome-activation-via-interaction-with-p47-phox-under-high-glucose-in-human-monocytic-cells
#8
Hisa Hui Ling Tseng, Chi Teng Vong, Yiu Wa Kwan, Simon Ming-Yuen Lee, Maggie Pui Man Hoi
Excessive production of reactive oxygen species (ROS) induced by hyperglycemia increased the secretion of interleukin-1β (IL-1β), which contributes to the pathogenesis of diabetes and its complications. Although high glucose (HG)-induced oxidative stress and aberrant Ca(2+) channels activity causes an increase in transmembrane Ca(2+) influx, however the relative contribution of Transient receptor potential (TRP) channels is not well studied. Here, we identified that HG (30 mM glucose for 48 h) induced the activation of the NLRP3-ASC inflammasome, leading to caspase-1 activation, and IL-1β and IL-18 secretion in human monocytic cell lines...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27694440/depletion-of-the-human-ion-channel-trpm2-in-neuroblastoma-demonstrates-its-key-role-in-cell-survival-through-modulation-of-mitochondrial-reactive-oxygen-species-and-bioenergetics
#9
Lei Bao, Shu-Jen Chen, Kathleen Conrad, Kerry Keefer, Thomas Abraham, John P Lee, JuFang Wang, Xue-Qian Zhang, Iwona Hirschler-Laszkiewicz, Hong-Gang Wang, Sinisa Dovat, Brian Gans, Muniswamy Madesh, Joseph Y Cheung, Barbara A Miller
Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in modulating cell survival following oxidant injury and is highly expressed in many cancers including neuroblastoma. Here, in xenografts generated from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology and in in vitro experiments, tumor growth was significantly inhibited and doxorubicin sensitivity increased. The hypoxia-inducible transcription factor 1/2α (HIF-1/2α) signaling cascade including proteins involved in oxidant stress, glycolysis, and mitochondrial function was suppressed by TRPM2 depletion...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27632706/inhibition-of-lanthanide-nanocrystal-induced-inflammasome-activation-in-macrophages-by-a-surface-coating-peptide-through-abrogation-of-ros-production-and-trpm2-mediated-ca-2-influx
#10
Han Yao, Yunjiao Zhang, Liu Liu, Youcui Xu, Xi Liu, Jun Lin, Wei Zhou, Pengfei Wei, Peipei Jin, Long-Ping Wen
Lanthanide-based nanoparticles (LNs) hold great promise in medicine. A variety of nanocrystals, including LNs, elicits potent inflammatory response through activation of NLRP3 inflammasome. We have previously identified an LNs-specific surface coating peptide RE-1, with the sequence of 'ACTARSPWICG', which reduced nanocrystal-cell interaction and abrogated LNs-induced autophagy and toxicity in both HeLa cells and liver hepatocytes. Here we show that RE-1 coating effectively inhibited LNs-induced inflammasome activation, mostly mediated by NLRP3, in mouse bone marrow derived macrophage (BMDM) cells, human THP-1 cells and mouse peritoneal macrophages and also reduced LNs-elicited inflammatory response in vivo...
November 2016: Biomaterials
https://www.readbyqxmd.com/read/27623379/a-radical-break-restraining-neutrophil-migration
#11
Jörg Renkawitz, Michael Sixt
When neutrophils infiltrate a site of inflammation, they have to stop at the right place to exert their effector function. In this issue of Developmental Cell, Wang et al. (2016) show that neutrophils sense reactive oxygen species via the TRPM2 channel to arrest migration at their target site.
September 12, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27618067/targeting-trpm2-in-ros-coupled-diseases
#12
REVIEW
Shinichiro Yamamoto, Shunichi Shimizu
Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca(2+)-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca(2+) signaling...
September 7, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27616276/role-of-transient-receptor-potential-melastatin-2-trpm2-channels-in-visceral-nociception-and-hypersensitivity
#13
Kenjiro Matsumoto, Kanako Takagi, Atsumi Kato, Takuya Ishibashi, Yasuo Mori, Kimihito Tashima, Atsushi Mitsumoto, Shinichi Kato, Syunji Horie
Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca(2+)-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity. Therefore, we investigated the expression of TRPM2 channels and their involvement in visceral nociception in normal physiology and under pathological conditions that cause visceral hypersensitivity in rats...
November 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27614169/endoglin-selectively-modulates-transient-receptor-potential-channel-expression-in-left-and-right-heart-failure
#14
Kevin J Morine, Vikram Paruchuri, Xiaoying Qiao, Mark Aronovitz, Gordon S Huggins, David DeNofrio, Michael S Kiernan, Richard H Karas, Navin K Kapur
INTRODUCTION: Transient receptor potential (TRP) channels are broadly expressed cation channels that mediate diverse physiological stimuli and include canonical (TRPC), melastatin (TRPM), and vanilloid (TRPV) subtypes. Recent studies have implicated a role for TRPC6 channels as an important component of signaling via the cytokine, transforming growth factor beta 1 (TGFβ1) in right (RV) or left ventricular (LV) failure. Endoglin (Eng) is a transmembrane glycoprotein that promotes TRPC6 expression and TGFβ1 activity...
August 21, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27569419/oxidant-sensing-by-trpm2-inhibits-neutrophil-migration-and-mitigates-inflammation
#15
Gang Wang, Luyang Cao, Xiaowen Liu, Nathan A Sieracki, Anke Di, Xi Wen, Yong Chen, Shalina Taylor, Xiaojia Huang, Chinnaswamy Tiruppathi, You-Yang Zhao, Yuanlin Song, Xiaopei Gao, Tian Jin, Chunxue Bai, Asrar B Malik, Jingsong Xu
Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to formyl peptide receptor 1 (FPR1) and subsequent FPR1 internalization and signaling inhibition...
September 12, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27562954/the-trpm2-channel-is-a-hypothalamic-heat-sensor-that-limits-fever-and-can-drive-hypothermia
#16
Kun Song, Hong Wang, Gretel B Kamm, Jörg Pohle, Fernanda de Castro Reis, Paul Heppenstall, Hagen Wende, Jan Siemens
Body temperature homeostasis is critical for survival and requires precise regulation by the nervous system. The hypothalamus serves as the principal thermostat that detects and regulates internal temperature. We demonstrate that the ion channel TRPM2 [of the transient receptor potential (TRP) channel family] is a temperature sensor in a subpopulation of hypothalamic neurons. TRPM2 limits the fever response and may detect increased temperatures to prevent overheating. Furthermore, chemogenetic activation and inhibition of hypothalamic TRPM2-expressing neurons in vivo decreased and increased body temperature, respectively...
September 23, 2016: Science
https://www.readbyqxmd.com/read/27533035/the-trpm2-ion-channel-is-required-for-sensitivity-to-warmth
#17
Chun-Hsiang Tan, Peter A McNaughton
Thermally activated ion channels are known to detect the entire thermal range from extreme heat (TRPV2), painful heat (TRPV1, TRPM3 and ANO1), non-painful warmth (TRPV3 and TRPV4) and non-painful coolness (TRPM8) through to painful cold (TRPA1). Genetic deletion of each of these ion channels, however, has only modest effects on thermal behaviour in mice, with the exception of TRPM8, the deletion of which has marked effects on the perception of moderate coolness in the range 10-25 °C. The molecular mechanism responsible for detecting non-painful warmth, in particular, is unresolved...
August 25, 2016: Nature
https://www.readbyqxmd.com/read/27513275/the-effects-of-bupivacaine-combined-with-different-adjuvants-on-block-onset-and-duration-and-on-ion-channel-expressions-scn9a-trpm-in-sciatic-nerve-block-in-rats
#18
Nurgül Dolu, Levent Şahin, Davut Sinan Kaplan, Tuncer Demir, Hasan Şimşek, Mehrican Şahin, Beyhan Cengiz
BACKGROUND/AIM: The objective of this experimental study was to examine the effects of epinephrine, dexmedetomidine, and clonidine added as adjuvants to bupivacaine on block onset and effect times, as well as the effects on the Na+ and Ca+2 channel gene expressions, which may indicate cell damage in the sciatic nerve cell membrane. MATERIALS AND METHODS: Rats were divided into five groups: Group S (sham), saline solution; Group B, bupivacaine; Group BD, bupivacaine + dexmedetomidine; Group BC, bupivacaine + clonidine; and Group BE, bupivacaine + epinephrine...
April 19, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/27499729/cyclic-adp-ribose-and-heat-regulate-oxytocin-release-via-cd38-and-trpm2-in-the-hypothalamus-during-social-or-psychological-stress-in-mice
#19
Jing Zhong, Sarwat Amina, Mingkun Liang, Shirin Akther, Teruko Yuhi, Tomoko Nishimura, Chiharu Tsuji, Takahiro Tsuji, Hong-Xiang Liu, Minako Hashii, Kazumi Furuhara, Shigeru Yokoyama, Yasuhiko Yamamoto, Hiroshi Okamoto, Yong Juan Zhao, Hon Cheung Lee, Makoto Tominaga, Olga Lopatina, Haruhiro Higashida
Hypothalamic oxytocin (OT) is released into the brain by cyclic ADP-ribose (cADPR) with or without depolarizing stimulation. Previously, we showed that the intracellular free calcium concentration ([Ca(2+)]i) that seems to trigger OT release can be elevated by β-NAD(+), cADPR, and ADP in mouse oxytocinergic neurons. As these β-NAD(+) metabolites activate warm-sensitive TRPM2 cation channels, when the incubation temperature is increased, the [Ca(2+)]i in hypothalamic neurons is elevated. However, it has not been determined whether OT release is facilitated by heat in vitro or hyperthermia in vivo in combination with cADPR...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27469928/transient-receptor-potential-melastatin-2-an-ion-channel-for-oxidative-stress-sensing
#20
(no author information available yet)
Transient receptor potential (TRP) channel is a superfamily of cation channels located on the cell membrane. TRP channels are classified into seven subfamilies based on the amino acid sequence homology,and transient receptor potential melastatin 2(TRPM2) is the second member of the TRPM subfamily. More evidences have revealed the important roles of TRPM2 in physiological and pathological events such as release of insulin from pancreatic Β-cells,inflammatory cytokines production from cells,and oxidative stress-induced cell death...
June 10, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
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