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TRPM2

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
December 27, 2017: 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
#8
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
#9
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
https://www.readbyqxmd.com/read/29209656/ionic-signalling-and-mitochondrial-dynamics
#10
Nada Abuarab, Fangfang Li, Asipu Sivaprasadarao
In age-related diseases, rise in intracellular reactive oxygen species (ROS) causes fragmentation of mitochondrial network. Our recent study demonstrated that ROS activation of TRPM2 (transient receptor potential melastatin-2) channels triggers lysosomal Zn2+ release that, in turn, triggers mitochondrial fragmentation. The findings provide new mechanistic insights that may have therapeutic implications.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29201240/glucagon-like-peptide-1-potentiates-glucose-stimulated-insulin-secretion-via-the-transient-receptor-potential-melastatin-2-channel
#11
Bo Pang, Sungjoon Kim, Daiqing Li, Zejun Ma, Bei Sun, Xiaona Zhang, Zhongming Wu, Liming Chen
The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic β-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29163217/different-principles-of-adp-ribose-mediated-activation-and-opposite-roles-of-the-nudt9-homology-domain-in-the-trpm2-orthologs-of-man-and-sea-anemone
#12
REVIEW
Frank Kühn, Cornelia Kühn, Andreas Lückhoff
A decisive element in the human cation channel TRPM2 is a region in its cytosolic C-terminus named NUDT9H because of its homology to the NUDT9 enzyme, a pyrophosphatase degrading ADP-ribose (ADPR). In hTRPM2, however, the NUDT9H domain has lost its enzymatic activity but serves as a binding domain for ADPR. As consequence of binding, gating of the channel is initiated. Since ADPR is produced after oxidative DNA damage, hTRPM2 mediates Ca(2+) influx in response to oxidative stress which may lead to cell death...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29156661/trpm2-channels-in-mitochondrial-dynamics-and-cancer
#13
EDITORIAL
Asipu Sivaprasadarao, Nada Abuarab, Fangfang Li
No abstract text is available yet for this article.
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146687/exercise-induces-muscle-fiber-type-switching-via-transient-receptor-potential-melastatin-2-trpm2-dependent-ca-2-signaling
#14
Seo-Ho Lee, Byung-Ju Kim, Dae-Ryoung Park, Uh-Hyun Kim
The aim of the present study was to examine whether transient receptor potential melastatin 2 (TRPM2) plays a role in muscle fiber type transition during exercise. Mice were trained at a speed of 12 m/min at a slope of 0 ° for 60 min 5 consecutive d/wk for 4-wk. Exhaustion tests were performed on the treadmill (the speed was set at 6 m/min at a slope of 0° and increased at a rate of 1 m/min every 6 min). Isolated primary skeletal muscle cells from TRPM2 knockout (KO) mice showed lower amplitudes of electrical stimuli (ES)-induced Ca(2+) signals when compared to wild-type (WT) mice, due to a defect in Ca(2+) influx...
November 16, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29143372/a-critical-role-of-trpm2-channel-in-a%C3%AE-42-induced-microglial-activation-and-generation-of-tumor-necrosis-factor-%C3%AE
#15
Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin-Hua Jiang
Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD...
November 16, 2017: Glia
https://www.readbyqxmd.com/read/29107864/trpm2-dependence-of-ros-induced-nlrp3-activation-in-alzheimer-s-disease
#16
Malihe Aminzadeh, Mehrdad Roghani, Azadeh Sarfallah, Gholam Hossein Riazi
Recent studies have shown that neuroinflammation plays an important role in Alzheimer's disease (AD). Microglial cells are responsible for the phagocytosis of Amyloid-β (Aβ). However, it has been demonstrated that in AD patients the efficiency of phagocytosis decreases due to proinflammatory cytokines, such as Interleukin-1β (IL-1β), which is produced through the activation of NLRP3 inflammasome. In this study, we aimed at deciphering the mechanism underlying the NLRP3 activation. The results showed that Aβ induces an increase in the level of reactive oxygen species (ROS)...
November 3, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29081064/long-non-coding-rna-trpm2-as-as-a-potential-biomarker-for-hepatocellular-carcinoma
#17
C Xu, Q Huang, C Zhang, W Xu, G Xu, X Zhao, X Liu, Y Du
BACKGROUND: There is increasing evidence that long non-coding RNAs are involved in hepatocellular carcinoma (HCC) tumorigenesis. The expression level of TRPM2-AS in HCC and its clinical association remain poorly defined. METHOD: qRT-PCR was performed to detect the expression of TRPM2-AS in 108 HCC patients. The correlations between TRPM2-AS expression and clinicopathological factors and prognosis were evaluated. The inference of TRPM2-AS to the proliferation and apoptosis of HCC cells was detected...
October 28, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29044760/development-of-novel-and-non-invasive-diagnostic-markers-for-lower-urinary-tract-symptoms-using-urothelial-cells-in-voided-urine
#18
Hiroshi Shimura, Takahiko Mitsui, Sachiko Tsuchiya, Tatsuya Miyamoto, Tatsuya Ihara, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuki Imai, Takanori Mochizuki, Masayuki Takeda
OBJECTIVES: We evaluated the association between lower urinary tract symptoms (LUTS) and the expression of connexin (Cx) and transient receptor potential (TRP) channel on urothelial cells non-invasively collected from voided urine in humans. METHODS: A total of 55 patients (36 males and 19 females, median age: 71 years old), who were followed up at University of Yamanashi Hospital, were enrolled in the present study. Urothelial cells were collected from voided urine of patients, and the mRNA expression of each subtype of Cxs and TRP channels was measured using quantitive real-time reverse transcription polymerase chain reaction...
October 17, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29034580/selective-inhibition-of-trpm2-channel-by-two-novel-synthesized-adpr-analogues
#19
Xiao Luo, Meng Li, Kaiyu Zhan, Wei Yang, Lihe Zhang, KeWei Wang, Peilin Yu, Liangren Zhang
Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5'-diphosphoribose (ADPR) analogues were synthesized and their activities and selectivity were evaluated. Whole-cell patch clamp recordings were employed for screen and evaluation of synthesized compounds...
October 15, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29019677/scalaradial-is-a-potent-inhibitor-of-transient-receptor-potential-melastatin-2-trpm2-ion-channels
#20
John G Starkus, Peter Poerzgen, Kristine Layugan, Kelly Galbraith Kawabata, Jun-Ichi Goto, Sayuri Suzuki, George Myers, Michelle Kelly, Reinhold Penner, Andrea Fleig, F David Horgen
TRPM2 is a Ca(2+)-permeable, nonselective cation channel that plays a role in oxidant-induced cell death, insulin secretion, and cytokine release. Few TRPM2 inhibitors have been reported, which hampers the validation of TRPM2 as a drug target. While screening our in-house marine-derived chemical library, we identified scalaradial and 12-deacetylscalaradial as the active components within an extract of an undescribed species of Cacospongia (class Demospongiae, family Thorectidae) that strongly inhibited TRPM2-mediated Ca(2+) influx in TRPM2-overexpressing HEK293 cells...
October 27, 2017: Journal of Natural Products
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