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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
#1
(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
#2
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
#3
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 (ADPR), the TRPM2 ligand. Objective: Because polymorphonuclear leukocytes (PMN) interaction with endothelial cells (ECs) generates ROS, 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 LPS challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2(iΔEC) )...
August 8, 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
#4
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
#5
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
https://www.readbyqxmd.com/read/28753206/trpm2-mediated-rise-in-mitochondrial-zn-2-promotes-palmitate-induced-mitochondrial-fission-and-pancreatic-%C3%AE-cell-death-in-rodents
#6
Fangfang Li, Tim S Munsey, Asipu Sivaprasadarao
Rise in plasma free fatty acids (FFAs) represents a major risk factor for obesity-induced type 2 diabetes. Saturated FFAs cause a progressive decline in insulin secretion by promoting pancreatic β-cell death through increased production of reactive oxygen species (ROS). Recent studies have demonstrated that palmitate (a C16-FFA)-induced rise in ROS causes β-cell death by triggering mitochondrial fragmentation, but the underlying mechanisms are unclear. Using the INS1-832/13 β-cell line, here we demonstrate that palmitate generates the ROS required for mitochondrial fission by activating NOX (NADPH oxidase)-2...
July 28, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28736241/oxytocin-release-via-activation-of-trpm2-and-cd38-in-the-hypothalamus-during-hyperthermia-in-mice-implication-for-autism-spectrum-disorder
#7
REVIEW
Haruhiro Higashida, Teruko Yuhi, Shirin Akther, Sarwat Amina, Jing Zhong, Mingkun Liang, Tomoko Nishimura, Hong-Xiang Liu, Olga Lopatina
Oxytocin (OT) is a critical molecule for social recognition that mediates social and emotional behaviors. OT is released during stress and acts as an anxiolytic factor. To know the precise molecular mechanisms underlying OT release into the brain during stress is important. It has been reported that intracellular concentrations of free calcium in the hypothalamic neurons are elevated by simultaneous stimulation of cyclic ADP-ribose (cADPR) and heat. We have reported in vitro and in vivo data that supports the idea that release of OT in the brain of male mice is regulated by cADPR and fever in relation to stress conditions...
July 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28678322/downregulated-long-non-coding-rna-trpm2-as-inhibits-cisplatin-resistance-of-non-small-cell-lung-cancer-cells-via-activation-of-p53-p66shc-pathway
#8
L-Y Ma, X-W Xie, L Ma, J-L Pang, X-M Xiong, H-D Zheng, X-L Shen, Z-G Wen, H-Y Wang
OBJECTIVE: Non-small cell lung cancer (NSCLC), as an ordinary malignant tumor, presents with high death rate and poor prognosis. Few literatures have explored the association between NSCLC development and lncRNAs expression. This study focuses on the important role of a novel lncRNA TRPM2-AS in the development of chemo-resistance in NSCLC. MATERIALS AND METHODS: The expression level of lncRNA TRPM2-AS was identified by using qRT-PCR assay. The apoptosis rate and the alteration of the cell cycle were detected by the flow cytometric analysis...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28671679/2-deoxyadenosine-5-diphosphoribose-is-an-endogenous-trpm2-superagonist
#9
Ralf Fliegert, Andreas Bauche, Adriana-Michelle Wolf Pérez, Joanna M Watt, Monika D Rozewitz, Riekje Winzer, Mareike Janus, Feng Gu, Annette Rosche, Angelika Harneit, Marianne Flato, Christelle Moreau, Tanja Kirchberger, Valerie Wolters, Barry V L Potter, Andreas H Guse
Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca(2+)-permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca(2+) signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca(2+) entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10...
September 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28668375/transient-receptor-potential-melastatin-2-channels-trpm2-mediate-neonatal-hypoxic-ischemic-brain-injury-in-mice
#10
Sammen Huang, Ekaterina Turlova, Feiya Li, Mei-Hua Bao, Vivian Szeto, Raymond Wong, Ahmed Abussaud, Haitao Wang, Shuzhen Zhu, Xinzheng Gao, Yasuo Mori, Zhong-Ping Feng, Hong-Shuo Sun
Transient receptor potential melastatin 2 (TRPM2), a calcium-permeable non-selective cation channel, is reported to mediate brain damage following ischemic insults in adult mice. However, the role of TRPM2 channels in neonatal hypoxic-ischemic brain injury remains unknown. We hypothesize that TRPM2(+/-) and TRPM2(-/-) neonatal mice have reduced hypoxic-ischemic brain injury. To study the effect of TRPM2 on neonatal brain damage, we used 2,3,5-triphenyltetrazolium chloride (TTC) staining to assess the infarct volume and whole brain imaging to assess morphological changes in the brain...
June 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28656459/involvement-of-thermosensitive-trp-channels-in-energy-metabolism
#11
REVIEW
Kunitoshi Uchida, Katsuya Dezaki, Takeshi Yoneshiro, Tatsuo Watanabe, Jun Yamazaki, Masayuki Saito, Toshihiko Yada, Makoto Tominaga, Yusaku Iwasaki
To date, 11 thermosensitive transient receptor potential (thermo-TRP) channels have been identified. Recent studies have characterized the mechanism of thermosensing by thermo-TRPs and the physiological role of thermo-TRPs in energy metabolism. In this review, we highlight the role of various thermo-TRPs in energy metabolism and hormone secretion. In the pancreas, TRPM2 and other TRPs regulate insulin secretion. TRPV2 expressed in brown adipocytes contributes to differentiation and/or thermogenesis. Sensory nerves that express TRPV1 promote increased energy expenditure by activating sympathetic nerves and adrenaline secretion...
September 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28633002/the-trpm2-channel-a-thermo-sensitive-metabolic-sensor
#12
Makiko Kashio, Makoto Tominaga
Living organisms continually experience changes in ambient temperature. To detect such temperature changes for adaptive behavioral responses, we evolved the ability to sense temperature. Thermosensitive transient receptor potential (TRP) channels, so-called thermo-TRPs, are involved in many physiologic functions in diverse organisms and constitute important temperature sensors. One of the important roles of thermo-TRPs is detecting ambient temperature in sensory neurons. Importantly, the functional expression of thermo-TRPs is observed not only in sensory neurons but also in tissues and cells that are not exposed to drastic temperature changes, indicating that thermo-TRPs are involved in many physiologic functions within the body's normal temperature range...
June 20, 2017: Channels
https://www.readbyqxmd.com/read/28620309/inhibition-of-the-trpm2-and-trpv1-channels-through-hypericum-perforatum-in-sciatic-nerve-injury-induced-rats-demonstrates-their-key-role-in-apoptosis-and-mitochondrial-oxidative-stress-of-sciatic-nerve-and-dorsal-root-ganglion
#13
Fuat Uslusoy, Mustafa Nazıroğlu, Bilal Çiğ
Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca(2+) entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28603015/activation-of-a-ca-2-dependent-cation-conductance-with-properties-of-trpm2-by-reactive-oxygen-species-in-lens-epithelial-cells
#14
Susanne Keckeis, Laura Wernecke, Daniel J Salchow, Nadine Reichhart, Olaf Strauß
Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca(2+)-dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca(2+)- and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca(2+)-activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells...
August 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28589630/synthesis-of-a-bioreversibly-masked-lipophilic-adenosine-diphosphate-ribose-derivative
#15
Katharina Pahnke, Chris Meier
The design of a bioreversibly protected lipophilic sugar nucleotide as a potential membrane-permeable precursor of adenosine diphosphate ribose (ADPR) is described. ADPR is the most potent activator of the transient receptor potential melastatin 2 (TRPM2) ion channel. Membrane-permeable, lipophilic derivatives of ADPR are of great interest as tools for study of the mechanism of TRPM2. The approach described here was based on our recently disclosed "DiPPro" and "TriPPPro" prodrug approaches developed for the intracellular delivery of nucleotides...
August 17, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28588083/science-signaling-podcast-for-6-june-2017-calcium-signaling-and-dry-mouth
#16
Indu Ambudkar, Annalisa M VanHook
This Podcast features a conversation with Indu Ambudkar, senior author of a Research Resource that appears in the 6 June 2017 issue of Science Signaling, about how activation of the cation channel TRPM2 is involved in radiation-induced dry mouth. Patients who receive radiation therapy for head and neck cancers often develop dry mouth as a side effect, and this condition is frequently permanent. Radiation does not kill cells in the salivary gland, yet it causes the acinar cells of the gland to reduce the amount of saliva they secrete...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28588080/radiation-inhibits-salivary-gland-function-by-promoting-stim1-cleavage-by-caspase-3-and-loss-of-soce-through-a-trpm2-dependent-pathway
#17
Xibao Liu, Baijuan Gong, Lorena Brito de Souza, Hwei Ling Ong, Krishna P Subedi, Kwong Tai Cheng, William Swaim, Changyu Zheng, Yasuo Mori, Indu S Ambudkar
Store-operated Ca(2+) entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2(+/+) , but not those from TRPM2(-/-) mice, displayed an increase in the concentrations of mitochondrial Ca(2+) and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28569571/curcumin-inhibits-oxidative-stress-induced-trpm2-channel-activation-calcium-ion-entry-and-apoptosis-values-in-sh-sy5y-neuroblastoma-cells-involvement-of-transfection-procedure
#18
Ahmi Öz, Ömer Çelik
Transient Receptor Potential (TRP) channels are mostly Ca(2+) permeable cation channels. Transient Receptor Potential Melastatin-like 2 (TRPM2) is expressed in neurological tissues such as brain, dorsal root ganglia (DRG) neurons, hippocampus and also liver, heart and kidney. The SH-SY5Y cells are mostly used as a cellular model of neurodegenerative diseases, Alzheimer's and Parkinson's diseases. Curcumin, shows phenolic structure, synthesized by Curcuma longa L. (turmeric), has powerful non-enzymatically antioxidant effects compared with Vitamin E...
June 1, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/28532624/tyrphostin-ag-related-compounds-attenuate-h2o2-induced-trpm2-dependent-and-independent-cellular-responses
#19
Shinichiro Yamamoto, Takahiro Toda, Ryo Yonezawa, Takaharu Negoro, Shunichi Shimizu
PURPOSE: TRPM2 is a Ca(2+)-permeable channel that is activated by H2O2. TRPM2-mediated Ca(2+) signaling has been implicated in the aggravation of inflammatory diseases. Therefore, the development of TRPM2 inhibitors to prevent the aggravation of these diseases is expected. We recently reported that some Tyrphostin AG-related compounds inhibited the H2O2-induced activation of TRPM2 by scavenging the intracellular hydroxyl radical. In the present study, we examined the effects of AG-related compounds on H2O2-induced cellular responses in human monocytic U937 cells, which functionally express TRPM2...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#20
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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