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https://www.readbyqxmd.com/read/28388577/il-6r-stat3-mir-204-feedback-loop-contributes-to-cisplatin-resistance-of-epithelial-ovarian-cancer-cells
#1
Xiaolan Zhu, Huiling Shen, Xinming Yin, Lulu Long, Xiaofang Chen, Fan Feng, Yueqin Liu, Peiqing Zhao, Yue Xu, Mei Li, Wenlin Xu, Yuefeng Li
Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28247021/store-operated-calcium-entry-is-essential-for-glial-calcium-signalling-in-cns-white-matter
#2
M Papanikolaou, A Lewis, A M Butt
'Calcium signalling' is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca(2+) stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them...
February 28, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28130109/hypotonicity-activates-a-voltage-dependent-membrane-conductance-in-n2a-neuroblastoma-cells
#3
Akiyuki Taruno, Yoshinori Marunaka
To maintain cellular and bodily homeostasis, cells respond to extracellular stimuli including osmotic stress by activating various ion channels, which have been implicated in many physiological and pathophysiological conditions. However, cellular osmosensory mechanisms remain elusive. Here, we report a novel voltage-dependent current in N2a cells activated by exposure to hypotonic stress. After a hypotonic challenge, N2a cells sequentially develop two distinct currents. The volume-regulated anion channel (VRAC) current emerges first and, after a delay, activation of a previously uncharacterized strongly outwardly rectifying current follows...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28122715/primary-cilia-regulate-the-osmotic-stress-response-of-renal-epithelial-cells-through-trpm3
#4
Brian J Siroky, Nancy K Kleene, Steven J Kleene, Charles D Varnell, Raven G Comer, Jialiu Liu, Lu Lu, Nolan W Pachciarz, John J Bissler, Bradley P Dixon
Primary cilia sense environmental conditions including osmolality, but whether cilia participate in osmotic response in renal epithelial cells is not known. Transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells, and that ciliary TRPM3 and TRPV4 mediate that response...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28112420/extracellular-signal-regulated-protein-kinase-c-jun-n-terminal-protein-kinase-and-calcineurin-regulate-transient-receptor-potential-m3-trpm3-induced-activation-of-ap-1
#5
Andrea Lesch, Oliver G Rössler, Gerald Thiel
Stimulation of transient receptor potential M3 (TRPM3) cation channels with pregnenolone sulfate induces an influx of Ca(2+) ions into the cells and a rise in the intracellular Ca(2+) concentration, leading to the activation of the activator protein-1 (AP-1) transcription factor. Here, we show that expression of a constitutively active mutant of the Ca(2+) /calmodulin-dependent protein phosphatase calcineurin attenuated pregnenolone sulfate-induced AP-1 activation in TRPM3-expressing cells. Likewise, expression of the regulatory B subunit of calcineurin reduced AP-1 activity in the cells following stimulation of TRPM3 channels...
January 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106668/primidone-inhibits-trpm3-and-attenuates-thermal-nociception-in-vivo
#6
Ute Krügel, Isabelle Straub, Holger Beckmann, Michael Schaefer
The melastatin-related transient receptor potential (TRP) channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat. Because TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties. Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors. Biophysical properties of channel inhibition were assessed using electrophysiological methods...
May 2017: Pain
https://www.readbyqxmd.com/read/28025236/otx2-defines-a-subgroup-of-atypical-teratoid-rhabdoid-tumors-with-close-relationship-to-choroid-plexus-tumors
#7
Anna Sophia Japp, Ludger Klein-Hitpass, Dorota Denkhaus, Torsten Pietsch
Atypical teratoid rhabdoid tumors (ATRT) are highly malignant brain tumors of early childhood that have been regarded as a homogenous entity characterized by inactivation of the SMARCB1/INI1 or SMARCA4/BRG1 genes as the only characteristic alteration. Recent studies suggest that similar to other embryonal tumors ATRT can also be divided into subgroups based on their mRNA or methylation profiles. Using microarray-based expression analysis of 12 patient ATRT specimens we demonstrated the existence of 2 subgroups of ATRT...
January 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27834303/single-nucleotide-polymorphisms-and-genotypes-of-transient-receptor-potential-ion-channel-and-acetylcholine-receptor-genes-from-isolated-b-lymphocytes-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-patients
#8
Sonya Marshall-Gradisnik, Samantha Johnston, Anu Chacko, Thao Nguyen, Peter Smith, Donald Staines
Objective The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca(2+)) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27733811/proinflammatory-cytokines-decrease-the-expression-of-genes-critical-for-rpe-function
#9
R Krishnan Kutty, William Samuel, Kaifa Boyce, Aswini Cherukuri, Todd Duncan, Cynthia Jaworski, Chandrasekharam N Nagineni, T Michael Redmond
PURPOSE: Proinflammatory cytokines interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) secreted by infiltrating lymphocytes or macrophages may play a role in triggering RPE dysfunction associated with age-related macular degeneration (AMD). Binding of these proinflammatory cytokines to their specific receptors residing on the RPE cell surface can activate signaling pathways that, in turn, may dysregulate cellular gene expression. The purpose of the present study was to investigate whether IFN-γ, TNF-α, and IL-1β have an adverse effect on the expression of genes essential for RPE function, employing the RPE cell line ARPE-19 as a model system...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27727448/impaired-calcium-mobilization-in-natural-killer-cells-from-chronic-fatigue-syndrome-myalgic-encephalomyelitis-patients-is-associated-with-transient-receptor-potential-melastatin-3-ion-channels
#10
T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca(2+) ) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56(dim) CD16(+) NK cells and CD56(bright) CD16(dim/-) NK cells...
February 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27716384/ion-channels-expression-and-function-are-strongly-modified-in-solid-tumors-and-vascular-malformations
#11
Antonella Biasiotta, Daniela D'Arcangelo, Francesca Passarelli, Ezio Maria Nicodemi, Antonio Facchiano
BACKGROUND: Several cellular functions relate to ion-channels activity. Physiologically relevant chains of events leading to angiogenesis, cell cycle and different forms of cell death, require transmembrane voltage control. We hypothesized that the unordered angiogenesis occurring in solid cancers and vascular malformations might associate, at least in part, to ion-transport alteration. METHODS: The expression level of several ion-channels was analyzed in human solid tumor biopsies...
October 4, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27614169/endoglin-selectively-modulates-transient-receptor-potential-channel-expression-in-left-and-right-heart-failure
#12
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...
November 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27533035/the-trpm2-ion-channel-is-required-for-sensitivity-to-warmth
#13
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/27464700/expression-of-transient-receptor-potential-channels-in-the-purified-human-pancreatic-%C3%AE-cells
#14
Francesco Marabita, Md Shahidul Islam
OBJECTIVE: Members of the transient receptor potential (TRP) channels are involved in mediating the electrical excitability and stimulus-secretion coupling in the pancreatic β-cells. The expression and the relative abundance of different TRP channels in the human β-cells are unknown. The objective of this study was to examine the expression of the TRP channels and their relative abundance in the human β-cell. METHODS: RNA sequencing data obtained from human islets, fluorescence-activated cell sorting-purified human β-cell and human pancreatic acinar cells were analyzed...
January 2017: Pancreas
https://www.readbyqxmd.com/read/27438705/the-dual-regulatory-role-of-mir-204-in-cancer
#15
REVIEW
Tianqi Li, Hongjie Pan, Runsheng Li
MicroRNAs (miRNAs) are a group of endogenous, small (about 22 nucleotides) non-coding RNAs which negatively regulate gene expressions. As one of them, miR-204 originates from the sixth intron of the transient receptor potential melastatin 3 (TRPM3) gene. Therefore, expression of miR-204 is under the control of the TRPM3 promoter and regulated by genetic and epigenetic mechanisms. miR-204 has been found to play the important roles in development of eyes and adipogenesis. Its pathological functions have been observed in a few diseases including pulmonary arterial hypertension, diabetes, and various types of cancers...
September 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27433342/diclofenac-a-nonsteroidal-anti-inflammatory-drug-is-an-antagonist-of-human-trpm3-isoforms
#16
Hiroka Suzuki, Eiji Sasaki, Ayumi Nakagawa, Yukiko Muraki, Noriyuki Hatano, Katsuhiko Muraki
The effects of diclofenac (Dic), an acetic acid derivative-type nonsteroidal anti-inflammatory drug, were examined on the function of transient receptor potential (TRP) melastatin (TRPM) 3 (TRPM3) in human embryonic kidney 293 cell-line (HEK293) cells with recombinant human TRPM3 isoforms (TRPM31325, TRPM3-3, TRPM3-9, and TRPM3-S) and in a neuroblastoma cell line human neuroblastoma IMR-32 cells (IMR-32 cells) derived from human peripheral neurons. TRPM3 responses evoked by pregnenolone sulfate (PregS) were effectively inhibited by Dic in a concentration-dependent manner in Ca(2+) measurement and electrophysiological assays...
June 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27356187/activation-of-gene-transcription-via-cim0216-a-synthetic-ligand-of-transient-receptor-potential-melastatin-3-trpm3-channels
#17
Sandra Rubil, Gerald Thiel
Several compounds have been proposed to stimulate TRPM3 Ca(2+) channels. We recently showed that stimulation of TRPM3 channels with pregnenolone sulfate activated the transcription factor AP-1, while other proposed TRPM3 ligands (nifedipine, D-erythro-sphingosine) exhibited either no or TRPM3-independent effects on gene transcription. Here, we have analyzed the transcriptional activity of CIM0216, a synthetic TRPM3 ligand proposed to have a higher potency and affinity for TRPM3 than pregnenolone sulfate. The results show that CIM0216 treatment of HEK293 cells expressing TRPM3 channels activated AP-1 and stimulated the transcriptional activation potential of c-Jun and c-Fos, 2 basic region leucine zipper transcription factors that constitute AP-1...
January 2, 2017: Channels
https://www.readbyqxmd.com/read/27328745/direct-modulation-of-trpm4-and-trpm3-channels-by-the-phospholipase-c-inhibitor-u73122
#18
Michael G Leitner, Niklas Michel, Marc Behrendt, Marlen Dierich, Sandeep Dembla, Bettina U Wilke, Maik Konrad, Moritz Lindner, Johannes Oberwinkler, Dominik Oliver
BACKGROUND AND PURPOSE: Signalling through phospholipase C (PLC) controls many cellular processes. Much information on the relevance of this important pathway has been derived from pharmacological inhibition of the enzymatic activity of PLC. We found that the most frequently employed PLC inhibitor, U73122, activates endogenous ionic currents in widely used cell lines. Given the extensive use of U73122 in research, we set out to identify these U73122-sensitive ion channels. EXPERIMENTAL APPROACH: We performed detailed biophysical analysis of the U73122-induced currents in frequently used cell lines...
August 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27308495/regulation-of-autophagy-by-two-products-of-one-gene-trpm3-and-mir-204
#19
Nicolas G Cost, Maria F Czyzyk-Krzeska
In clear cell renal cell carcinoma (ccRCC), oncogenic autophagy dependent on microtubule-associated protein 1 light chain 3 α and β (LC3A and LC3B) is stimulated by activity of the transient receptor potential melastatin 3 (TRPM3) channel through multiple complementary mechanisms. The Von Hippel-Lindau (VHL) tumor suppressor represses this oncogenic autophagy in a coordinated manner through the activity of miR-204, which is expressed from intron 6 of the gene encoding TRPM3. TRPM3 represents an actionable target for ccRCC treatment...
October 2015: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27246981/differences-in-somatic-mutation-landscape-of-hepatocellular-carcinoma-in-asian-american-and-european-american-populations
#20
Song Yao, Christopher Johnson, Qiang Hu, Li Yan, Biao Liu, Christine B Ambrosone, Jianmin Wang, Song Liu
The incidence rate of hepatocellular carcinoma (HCC) is higher in populations of Asian ancestry than European ancestry (EA). We sought to investigate HCC mutational differences between the two populations, which may reflect differences in the prevalence of etiological factors. We compared HCC somatic mutations in patients of self-reported Asian American and EA from The Cancer Genome Atlas (TCGA), and assessed associations of tumor mutations with established HCC risk factors. Although the average mutation burden was similar, TP53 and RB1 were mutated at a much higher frequency in Asian Americans than in EAs (TP53: 43% vs...
June 28, 2016: Oncotarget
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