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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
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 has been identified in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilisation has yet to be determined. Fifteen CFS/ME patients (mean age 48.82 ± 9.83 years) and 25 health controls (mean age 39.2 ± 12.12 years) were examined. Isolated 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...
October 11, 2016: Clinical and Experimental Immunology
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
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...
August 21, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
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
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...
July 25, 2016: Pancreas
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...
July 20, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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
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...
June 29, 2016: Channels
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
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
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...
May 26, 2016: Oncotarget
T Nguyen, D Staines, B Nilius, P Smith, S Marshall-Gradisnik
BACKGROUND: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation...
2016: Biological Research
Xudong Wu, Artur A Indzhykulian, Paul D Niksch, Roxanna M Webber, Miguel Garcia-Gonzalez, Terry Watnick, Jing Zhou, Melissa A Vollrath, David P Corey
Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group...
2016: PloS One
Sonya Marshall-Gradisnik, Teilah Huth, Anu Chacko, Samantha Johnston, Pete Smith, Donald Staines
AIM: The aim of this paper was to determine natural killer (NK) cytotoxic activity and if single nucleotide polymorphisms (SNPs) and genotypes in transient receptor potential (TRP) ion channels and acetylcholine receptors (AChRs) were present in isolated NK cells from previously identified myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients. SUBJECTS AND METHODS: A total of 39 ME/CFS patients (51.69±2 years old) and 30 unfatigued controls (47...
2016: Application of Clinical Genetics
Valentina Malafoglia, Lorenzo Traversetti, Floriano Del Grosso, Massimiliano Scalici, Filomena Lauro, Valeria Russo, Tiziana Persichini, Daniela Salvemini, Vincenzo Mollace, Massimo Fini, William Raffaeli, Carolina Muscoli, Marco Colasanti
The ability of mammals to feel noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors, which express specific membrane receptors, such as the Transient Receptor Potential (TRP) family. Here, we show that one of the most important nociceptive-like pathways is conserved in the freshwater coelenterate Hydra vulgaris, the most primitive organism possessing a nervous system. In particular, we found that H. vulgaris expresses TRPM3, a nociceptor calcium channel involved in the detection of noxious heat in mammals...
2016: PloS One
Lusine Demirkhanyan, Kunitoshi Uchida, Makoto Tominaga, Eleonora Zakharian
No abstract text is available yet for this article.
July 3, 2016: Channels
Arun Narayanankutty, Icela Palma-Lara, Gandhi Pavón-Romero, Gloria Pérez-Rubio, Ángel Camarena, Luis M Teran, Ramcés Falfán-Valencia
INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma rhinosinusitis and poliposis; ingestion of aspirin or other non-steroid anti-inflammatory drugs exacerbate asthma-like symptoms. The pathogenesis of AERD is unknown, and genetic and environmental factors contribute to the disease. Our objective is identifying polymorphisms associated with susceptibility in a Mexican mestizo population. METHODS: Primarily we performed custom Illumina goldengate array-based genotyping of 1512 SNPs, carefully selected from a variety of acute/chronic inflammatory lung conditions previously reported...
April 2016: Lung
Katharina Held, Thomas Voets, Joris Vriens
Opening and closing of voltage-gated cation channels allows the regulated flow of cations such as Na(+), K(+), and Ca(2+) across cell membranes, which steers essential physiological processes including shaping of action potentials and triggering Ca(2+)-dependent processes. Classical textbooks describe the voltage-gated cation channels as membrane proteins with a single, central aqueous pore. In recent years, however, evidence has accumulated for the existence of additional ion permeation pathways in this group of cation channels, distinct from the central pore, which here we collectively name non-canonical pores...
2016: Reviews of Physiology, Biochemistry and Pharmacology
Yu Rang Park, Jung Nyeo Chun, Insuk So, Hwa Jung Kim, Seunghee Baek, Ju-Hong Jeon, Soo-Yong Shin
BACKGROUND: Experimental evidence has suggested that transient receptor potential (TRP) channels play a crucial role in tumor biology. However, clinical relevance and significance of TRP channels in cancer remain largely unknown. MATERIALS AND METHODS: We applied a data-driven approach to dissect the expression landscape of 27 TRP channel genes in 14 types of human cancer using International Cancer Genome Consortium data. RESULTS: TRPM2 was found overexpressed in most tumors, whereas TRPM3 was broadly down-regulated...
January 2016: Cancer Genomics & Proteomics
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