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https://www.readbyqxmd.com/read/29209656/ionic-signalling-and-mitochondrial-dynamics
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28970008/the-trpm2-ion-channel-contributes-to-cytokine-hyperproduction-in-a-mouse-model-of-down-syndrome
#12
Fabienne Gally, Deviyani M Rao, Carsten Schmitz, Kelley L Colvin, Michael E Yeager, Anne-Laure Perraud
Trisomy 21 (Down Syndrome, DS) is the most common chromosomal anomaly. Although DS is mostly perceived as affecting cognitive abilities and cardiac health, individuals with DS also exhibit dysregulated immune functions. Levels of pro-inflammatory cytokines are increased, but intrinsic alterations of innate immunity are understudied in DS. Furthermore, elevated Reactive Oxygen Species (ROS) are well documented in individuals with DS, further exacerbating inflammatory processes. Chronic inflammation and oxidative stress are often precursors of subsequent tissue destruction and pathologies, which affect a majority of persons with DS...
September 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28924972/targeting-nociceptive-trp-channels-to-treat-chronic-pain-current-state-of-the-field
#13
REVIEW
Magdalene M Moran, Arpad Szallasi
Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of Transient Receptor Potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically...
September 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28876960/trpm2-shredding-the-mitochondrial-network
#14
Fangfang Li, Nada Abuarab, Asipu Sivaprasadarao
No abstract text is available yet for this article.
September 6, 2017: Channels
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#15
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820960/principles-of-chemical-biology-iron-and-cscs-histone-acylation-sans-enzymes-eliciting-silent-gene-clusters-and-2-deoxy-adpr-as-a-second-messenger
#16
(no author information available yet)
This month: Lysosomal iron linked to cell death in cancer stem cells, non-enzymatic catalyst SynCAc for histone acylation, cytotoxins ivermectin and etoposide bring new anti-fungals out of the crypt, and 2'-deoxy-ADPR as second messenger activating TRPM2.
August 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28790515/transient-receptor-potential-melastatin-channel-family-member-2-friend-or-foe
#17
Joseph Y Cheung, Barbara A Miller
Transient receptor potential melastatin 2 (Trpm2) channels are nonvoltage-activated channels permeable to monovalent and divalent cations, and are expressed in heart, brain, kidney, vasculature, and hematopoietic cells. Trpm2 is overexpressed in bladder, lung, breast, liver, head, and neck cancers. Classically, Trpm2 activation induces cell injury and death by Ca(2+) overload or enhanced inflammatory response. Recent studies show that Trpm2 protects lungs from endotoxin-induced injury by reducing reactive oxygen species production in phagocytes; and improves cardiac function after ischemia-reperfusion injury by preserving mitochondrial respiration and cellular adenosine triphosphate levels while decreasing reactive oxygen species levels...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790198/neutrophil-activation-of-endothelial-cell-expressed-trpm2-mediates-transendothelial-neutrophil-migration-and-vascular-injury
#18
Manish Mittal, Saroj Nepal, Yoshikazu Tsukasaki, Claudie M Hecquet, Dheeraj Soni, Jalees Rehman, Chinnaswamy Tiruppathi, Asrar B Malik
RATIONALE: TRPM2 (transient receptor potential melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca(2+) entry in response to intracellular generation of adenosine diphosphoribose-the TRPM2 ligand. OBJECTIVE: Because polymorphonuclear neutrophils (PMN) interaction with ECs generates reactive oxygen species, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. METHODS AND RESULTS: We observed defective PMN transmigration in response to lipopolysaccharide challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2(iΔEC) )...
October 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28775320/modulation-of-activation-and-inactivation-by-ca-2-and-2-apb-in-the-pore-of-an-archetypal-trpm-channel-from-nematostella-vectensis
#19
Frank J P Kühn, Winking Mathis, Kühn Cornelia, Daniel C Hoffmann, Andreas Lückhoff
The archetypal TRPM2-like channel of the sea anemone Nematostella vectensis is gated by ADPR like its human orthologue but additionally exhibits properties of other vertebrate TRPM channels. Thus it can help towards an understanding of gating and regulation of the whole subfamily. To elucidate further the role of Ca(2+) as a co-factor of ADPR, we exploited 2-aminoethyl diphenylborinate (2-APB), previously shown to exert either inhibitory or stimulatory effects on diverse TRPM channels, or both in a concentration-dependent manner...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765513/high-glucose-induced-ros-activates-trpm2-to-trigger-lysosomal-membrane-permeabilization-and-zn-2-mediated-mitochondrial-fission
#20
Nada Abuarab, Tim S Munsey, Lin-Hua Jiang, Jing Li, Asipu Sivaprasadarao
Diabetic stress increases the production of reactive oxygen species (ROS), leading to mitochondrial fragmentation and dysfunction. We hypothesized that ROS-sensitive TRPM2 channels mediated diabetic stress-induced mitochondrial fragmentation. We found that chemical inhibitors, RNAi silencing, and genetic knockout of TRPM2 channels abolished the ability of high glucose to cause mitochondrial fission in endothelial cells, a cell type that is particularly vulnerable to diabetic stress. Similar to high glucose, increasing ROS in endothelial cells by applying H2O2 induced mitochondrial fission...
August 1, 2017: Science Signaling
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