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TRPM2

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https://www.readbyqxmd.com/read/29671419/trpm2-a-candidate-therapeutic-target-for-treating-neurological-diseases
#1
REVIEW
Jillian Corinne Belrose, Michael Frederick Jackson
Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+ )-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29668377/pulsed-infrared-releases-ca-2-from-the-endoplasmic-reticulum-of-cultured-spiral-ganglion-neurons
#2
John N Barrett, Samantha Rincon, Jayanti Singh, Cristina Matthewman, Julio Pasos, Ellen F Barrett, Suhrud M Rajguru
We investigated the effects of pulsed infrared radiation (IR, 1863 nm) stimulation on cytosolic [Ca2+ ] in inner ear spiral ganglion neurons cultured from day 4 postnatal mice and loaded with a fluorescent Ca2+ indicator (fluo-4, -5F or -5N). IR pulse trains (200 µs, 200-250 Hz, 2-5 s) delivered via an optical fiber coupled to IR source produced a rapid, transient temperature increase of 6-11ºC (above a baseline of 24-30 ºC) and evoked transient increases in both nuclear and cytosolic [Ca2+ ] of 0.20 - 1...
April 18, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29620272/trpm2-promotes-the-proliferation-and-invasion-of-pancreatic-ductal-adenocarcinoma
#3
Rui Lin, Yufeng Wang, Quanning Chen, Zhongyan Liu, Shuai Xiao, Bingyi Wang, Baomin Shi
The aim of the present study was to investigate transient receptor potential cation channel subfamily M member 2 (TRPM2), a promising therapeutic target and biomarker for pancreatic ductal adenocarcinoma (PDAC) prognosis, in addition to determining its effects regarding tumor progression and invasion. PDAC is a fatal disease with a poor prognosis, and its associated pathogenic molecular mechanisms remain to be determined. In the present study, combined analysis using genomic and transcriptomic data from two PDAC studies was performed to discover a survival‑associated biomarker of PDAC...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29565641/role-of-transient-receptor-potential-melastatin-2-in-surgical-inflammation-and-dysmotility-in-a-mouse-model-of-post-operative-ileus
#4
Kenjiro Matsumoto, Hiroki Kawanaka, Masatoshi Hori, Kosuke Kusamori, Daichi Utsumi, Takuya Tsukahara, Kikuko Amagase, Syunji Horie, Akira Yamamoto, Hiroshi Ozaki, Yasuo Mori, Shinichi Kato
In this study, we investigated the role of transient receptor potential melastatin 2 (TRPM2), a nonselective cation channel abundantly expressed in inflammatory cells such as macrophages, in the development of post-operative ileus, a complication of abdominal surgery characterized by gastrointestinal dysmotility. In wild type mice, we found that intestinal manipulation, a maneuver that elicits symptoms typical of post-operative ileus, delays the transit of fluorescein-labeled dextran, promotes the infiltration of CD68+ macrophages, Ly6B...
March 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29552700/trpm2-and-warmth-sensation
#5
REVIEW
Chun-Hsiang Tan, Peter A McNaughton
The abilities to detect warmth and heat are critical for the survival of all animals, both in order to be able to identify suitable thermal environments for the many different activities essential for life and to avoid damage caused by extremes of temperature. Several ion channels belonging to the TRP family are activated by non-noxious warmth or by heat and are therefore plausible candidates for thermal detectors, but identifying those that actually regulate warmth and heat detection in intact animals has proven problematic...
March 19, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29542681/the-role-of-trpm2-channels-in-neurons-glial-cells-and-the-blood-brain-barrier-in-cerebral-ischemia-and-hypoxia
#6
REVIEW
Ekaterina Turlova, Zhong-Ping Feng, Hong-Shuo Sun
Stroke is one of the major causes of mortality and morbidity worldwide, yet novel therapeutic treatments for this condition are lacking. This review focuses on the roles of the transient receptor potential melastatin 2 (TRPM2) ion channels in cellular damage following hypoxia-ischemia and their potential as a future therapeutic target for stroke. Here, we highlight the complex molecular signaling that takes place in neurons, glial cells and the blood-brain barrier following ischemic insult. We also describe the evidence of TRPM2 involvement in these processes, as shown from numerous in vitro and in vivo studies that utilize genetic and pharmacological approaches...
March 15, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29507145/trpm2-channel-aggravates-cns-inflammation-and-cognitive-impairment-via-activation-of-microglia-in-chronic-cerebral-hypoperfusion
#7
Jun Miyanohara, Masashi Kakae, Kazuki Nagayasu, Takayuki Nakagawa, Yasuo Mori, Ken Arai, Hisashi Shirakawa, Shuji Kaneko
Chronic cerebral hypoperfusion is a characteristic seen in widespread CNS diseases, including neurodegenerative and mental disorders, and is commonly accompanied by cognitive impairment. Recently, several studies demonstrated that chronic cerebral hypoperfusion can induce the excessive inflammatory responses that precede neuronal dysfunction; however, the precise mechanism of cognitive impairment due to chronic cerebral hypoperfusion remains unknown. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable channel that is abundantly expressed in immune cells and is involved in aggravation of inflammatory responses...
March 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29495939/disruption-of-transient-receptor-potential-melastatin-2-decreases-elastase-release-and-bacterial-clearance-in-neutrophils
#8
XiaoWei Qian, Hang Zhao, XinZhong Chen, Jun Li
Elastase released by neutrophils is critical for eliminating Gram-negative bacteria. Ca2+ influx plays a key role in elastase release and bacterial clearance in neutrophils. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable cation channel highly expressed in neutrophils. Here, we explore the role and possible mechanism of TRPM2 in bacterial clearance in TRPM2 knockout (TRPM2-KO) mice neutrophils. After exposure to Escherichia coli, TRPM2-KO bone marrow neutrophils (BMNs) had increased bacterial burden and decreased elastase release...
February 2018: Innate Immunity
https://www.readbyqxmd.com/read/29491840/neuropathic-pain-delving-into-the-oxidative-origin-and-the-possible-implication-of-transient-receptor-potential-channels
#9
REVIEW
Cristina Carrasco, Mustafa Naziroǧlu, Ana B Rodríguez, José A Pariente
Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI), cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29490946/trpm2-mediates-neutrophil-killing-of-disseminated-tumor-cells
#10
Maya Gershkovitz, Yaki Caspi, Tanya Fainsod-Levi, Ben Katz, Janna Michaeli, Saleh Khawaled, Shaya Lev, Lola Polyansky, Merav E Shaul, Ronit Vogt Sionov, Leonor Cohen-Daniel, Rami I Aqeilan, Yoav Shaul, Yasuo Mori, Rotem Karni, Zvi G Fridlender, Alexander M Binshtok, Zvi Granot
Neutrophils play a critical role in cancer, with both pro- and anti-tumor neutrophil subpopulations reported. The anti-tumor neutrophil subpopulation has the capacity to kill tumor cells and limit metastatic spread, yet not all tumor cells are equally susceptible to neutrophil cytotoxicity. Since cells that evade neutrophils have greater chances of forming metastases, we explored the mechanism neutrophils employ to kill tumor cells. Neutrophil cytotoxicity was previously shown to be mediated by secretion of H2O2...
February 28, 2018: Cancer Research
https://www.readbyqxmd.com/read/29463868/cd38-promotes-pristane-induced-chronic-inflammation-and-increases-susceptibility-to-experimental-lupus-by-an-apoptosis-driven-and-trpm2-dependent-mechanism
#11
Sonia García-Rodríguez, Antonio Rosal-Vela, Davide Botta, Luz M Cumba Garcia, Esther Zumaquero, Verónica Prados-Maniviesa, Daniela Cerezo-Wallis, Nicola Lo Buono, José-Ángel Robles-Guirado, Salvador Guerrero, Elena González-Paredes, Eduardo Andrés-León, Ángel Corbí, Matthias Mack, Friedrich Koch-Nolte, Ramón Merino, Mercedes Zubiaur, Frances E Lund, Jaime Sancho
In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38-/- ) but not ART2-deficient (Art2-/- ) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hi Ly6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29416015/multiple-molecular-mechanisms-form-a-positive-feedback-loop-driving-amyloid-%C3%AE-42-peptide-induced-neurotoxicity-via-activation-of-the-trpm2-channel-in-hippocampal-neurons
#12
Xin Li, Lin-Hua Jiang
Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer's disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ42 activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ42-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29373067/role-of-trp-channels-in-dinoflagellate-mechanotransduction
#13
J B Lindström, N T Pierce, M I Latz
Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences...
October 2017: Biological Bulletin
https://www.readbyqxmd.com/read/29369356/hypertonicity-induced-cation-channels-hiccs-in-hepg2-cells-architecture-and-role-in-proliferation-vs-apoptosis
#14
Björn Koos, Jens Christmann, Sandra Plettenberg, Domenic Käding, Julia Becker, Melody Keteku, Christian Klein, Sarah Imtiaz, Petra Janning, Philippe I H Bastiaens, Frank Wehner
Hypertonicity-induced cation channels (HICCs) are substantial elements in the regulatory volume increase (RVI) of osmotically shrunken cells. Under isotonic conditions, they are key effectors in the volume gain preceding proliferation; HICC repression, in turn, significantly increases apoptosis rates. Despite these fundamental roles of HICCs in cell physiology, very little is known concerning the actual molecular architecture of these channels. Here, an siRNA screening on putative ion channels and transporters was performed, in HepG2 cells, with the velocity of RVI as the read-out; in this first run, δENaC, TRPM2 and TRPM5 could be identified as HICCs...
January 25, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#15
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29327205/nociceptive-roles-of-trpm2-ion-channel-in-pathologic-pain
#16
REVIEW
Yongwoo Jang, Pyung Sun Cho, Young Duk Yang, Sun Wook Hwang
Pain is a protective mechanism that enables us to avoid potentially harmful environments. However, when pathologically persisted and aggravated under severely injured or inflamed conditions, pain often reduces the quality of life and thus is considered as a disease to eliminate. Inflammatory and/or neuropathic mechanisms may exaggerate interactions between damaged tissues and neural pathways for pain mediation. Similar mechanisms also promote the communication among cellular participants in synapses at spinal or higher levels, which may amplify nociceptive firing and subsequent signal transmission, deteriorating the pain sensation...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29303602/melatonin-attenuates-chronic-cough-mediated-by-oxidative-stress-via-transient-receptor-potential-melastatin-2-in-guinea-pigs-exposed-to-particulate-matter-2-5
#17
Zhenjun Ji, Zhen Wang, Zhe Chen, Hao Jin, Chen Chen, Senlin Chai, Haining Lv, Ling Yang, Yakun Hu, Rong Dong, Kefang Lai
The aim of this study was to investigate the effects of melatonin on oxidative stress, the expression of transient receptor potential melastatin-2 (TRPM2) in guinea pig brains, and the influence of melatonin on oxidative stress in lungs and airway inflammation induced by particulate matter 2.5 (PM2.5). A particle suspension (0.1 g/ml) was nasally administered to the guinea pigs to prepare a PM2.5 exposure model. Cough frequency and cough incubation period were determined through RM6240B biological signal collection and disposal system...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29282613/regulation-of-pain-and-itch-by-trp-channels
#18
REVIEW
Carlene Moore, Rupali Gupta, Sven-Eric Jordt, Yong Chen, Wolfgang B Liedtke
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur...
February 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29250536/transient-receptor-potential-melastatin-2-negatively-regulates-lps-atp-induced-caspase-1-dependent-pyroptosis-of-bone-marrow-derived-macrophage-by-modulating-ros-production
#19
Haihong Wang, Xinyi Zhou, Hui Li, Xiaowei Qian, Yan Wang, Liang Ma
Background: Pyroptosis, a new form of cell death, which has special morphological characteristics, depends on caspase-1 activation and occupies an important role in inflammatory immune diseases and ischemia-reperfusion injury. ROS is a common activator of NLR/caspase-1. Transient receptor potential melastatin 2 (TRPM2), a selective cation channel, is involved in inflammatory regulation. This study was designed to explore the role of TRPM2 in activating caspase-1 and caspase-1-dependent pyroptosis of mouse BMDMs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29235496/involvement-of-trpm2-and-trpv1-channels-on-hyperalgesia-apoptosis-and-oxidative-stress-in-rat-fibromyalgia-model-protective-role-of-selenium
#20
Esra Yüksel, Mustafa Nazıroğlu, Mehmet Şahin, Bilal Çiğ
Fibromyalgia (FM) results in pain characterized by low selenium (Se) levels, excessive Ca2+ influx, reactive oxygen species (ROS) production, and acidic pH. TRPM2 and TRPV1 are activated by ROS and acid; nevertheless, their roles have not been elucidated in FM. Therefore, we investigated the contribution of TRPM2 and TRPV1 to pain, oxidative stress, and apoptosis in a rat model of FM and the therapeutic potential of Se. Thirty-six rats were divided into four groups: control, Se, FM, and FM + Se. The Se treatment reduced the FM-induced increase in TRPM2 and TRPV1 currents, pain intensity, intracellular free Ca2+ , ROS, and mitochondrial membrane depolarization in the sciatic (SciN) and dorsal root ganglion (DRGN) neurons...
December 13, 2017: Scientific Reports
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