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Valentina Gallo, F Nicole Dijk, John W Holloway, Susan M Ring, Gerard H Koppelman, Dirkje S Postma, David P Strachan, Raquel Granell, Johan C de Jongste, Vincent W V Jaddoe, Herman T den Dekker, Liesbeth Duijts, A John Henderson, Seif O Shaheen
BACKGROUND: Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. METHODS: We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7...
October 25, 2016: Pediatric Allergy and Immunology
H Viisanen, H Chapman, H Wei, M Lasierra Losada, A Koivisto, K E Akerman, A Pertovaara
Methylglyoxal (MG) is a reactive carbonyl compound generated in diabetes mellitus. MG is an established transient receptor potential ankyrin 1 (TRPA1) channel agonist that contributes to TRPA1-mediated diabetic pain hypersensitivity. Here we studied whether exposure to diabetes and thereby to elevated endogenous MG modulates hypersensitivity induced by intradermal MG. Moreover, since diabetes induces endoplasmic reticulum (ER) stress, we compared the role of TRPA1 in diabetes and ER stress by assessing whether tunicamycin-induced ER stress, without diabetes, produces TRPA1-mediated pain hypersensitivity and by assessing whether ER stress and diabetes have similar modulatory effects on MG-induced hypersensitivity...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Guangda Peng, Makiko Kashio, Tianbang Li, Xiaofeng Dong, Makoto Tominaga, Tatsuhiko Kadowaki
The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is conserved between many arthropods, and in some has been shown to function as a chemosensor for noxious compounds. Activation of arthropod TRPA1 channels by temperature fluctuations has been tested in only a few insect species, and all of them were shown to be activated by heat. The recent identification of chemosensitive TRPA1 channels from two honey bee ectoparasitic mite species (VdTRPA1 and TmTRPA1) have provided an opportunity to study the temperature-dependent activation and the temperature-associated physiological functions of TRPA1 channels in non-insect arthropods...
2016: Frontiers in Physiology
Micheline N Ngaki, Bing Wang, Binod B Sahu, Subodh K Srivastava, Mohammad S Farooqi, Sekhar Kambakam, Sivakumar Swaminathan, Madan K Bhattacharyya
Fusarium virguliforme causes the serious disease sudden death syndrome (SDS) in soybean. Host resistance to this pathogen is partial and is encoded by a large number of quantitative trait loci, each conditioning small effects. Breeding SDS resistance is therefore challenging and identification of single-gene encoded novel resistance mechanisms is becoming a priority to fight this devastating this fungal pathogen. In this transcriptomic study we identified a few putative soybean defense genes, expression of which is suppressed during F...
2016: PloS One
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Yun Ling, Zhuang-Li Hu, Qing-Li Meng, Peng Fang, Hai-Xia Liu
Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Yao Lu, Honit Piplani, Stacy L McAllister, Carl M Hurt, Eric R Gross
BACKGROUND: Recent evidence suggests that cross talk exists between cellular pathways important for pain signaling and ischemia-reperfusion injury. Here, the authors address whether the transient receptor potential ankyrin 1 (TRPA1) channel, important in pain signaling, is present in cardiac myocytes and regulates cardiac ischemia-reperfusion injury. METHODS: For biochemical analysis of TRPA1, techniques including quantitative polymerase chain reaction, Western blot, and immunofluorescence were used...
September 30, 2016: Anesthesiology
Bernhard Stenger, Tanja Popp, Harald John, Markus Siegert, Amelie Tsoutsoulopoulos, Annette Schmidt, Harald Mückter, Thomas Gudermann, Horst Thiermann, Dirk Steinritz
Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target...
October 13, 2016: Archives of Toxicology
S A Coavoy-Sánchez, L Rodrigues, S A Teixeira, A G Soares, R Torregrossa, M E Wood, M Whiteman, S K P Costa, M N Muscará
Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved...
October 6, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Fangfei Qu, Damaris N Lorenzo, Samantha J King, Rebecca Brooks, James E Bear, Vann Bennett
Endosomal membrane trafficking requires coordination between phosphoinositide lipids, Rab GTPases, and microtubule-based motors to dynamically determine endosome identity and promote long-range organelle transport. Here we report that Ankyrin-B (AnkB), through integrating all three systems, functions as a critical node in the protein circuitry underlying polarized recycling of α5β1-integrin in mouse embryonic fibroblasts, which enables persistent fibroblast migration along fibronectin gradients. AnkB associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles in fibroblasts and binds dynactin to promote their long-range motility...
October 8, 2016: ELife
József Kun, Anikó Perkecz, Lorenz Knie, György Sétáló, Tamás Tornóczki, Erika Pintér, Ágnes Bán
OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with antigen-specific and non-specific mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel activated by noxious stimuli such as oxidative stress products evoking pain and release of proinflammatory mediators from sensory nerve endings culminating in neurogenic inflammation. Extraneuronal TRPA1s e.g. on immune cells possess yet unkown functions. SUBJECTS AND METHODS: We studied the buccal mRNA expression (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors, and key OLP mediator transcripts in oral mucosa samples of healthy volunteers (n=9), OLP patients (n=43) and OLP-like hyperkeratotic diseases (n=12)...
October 8, 2016: Oral Diseases
Na Zhang, Feiming Ye, Wei Zhu, Dexing Hu, Changchen Xiao, Jinliang Nan, Sheng'an Su, Yingchao Wang, Mingfei Liu, Kanglu Gao, Xinyang Hu, Jinghai Chen, Hong Yu, Xiaojie Xie, Jian'an Wang
Cardiac ankyrin repeat protein (CARP) is a nuclear transcriptional co-factor that has additional functions in the myoplasm as a component of the muscle sarcomere. Previous studies have demonstrated increased expression of CARP in cardiovascular diseases, however, its role in cardiomyocyte apoptosis is unclear and controversial. In the present study, we investigated possible roles of CARP in hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected with adenovirus encoding Flag-tagged CARP (Ad-CARP) and lentivirus encoding CARP targeted shRNA (sh-CARP), respectively...
October 3, 2016: Biochimica et Biophysica Acta
Sebastian Guettler
The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to capture substrates via Tankyrase-binding peptide motifs. In this issue of Structure, Eisemann et al. (2016) describe how the signaling protein AXIN can access and conformationally adapt the multivalent ankyrin repeat region of Tankyrase and discuss potential implications for enzymatic substrate modification.
October 4, 2016: Structure
David Albrecht, Christian M Winterflood, Mohsen Sadeghi, Thomas Tschager, Frank Noé, Helge Ewers
The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development...
October 10, 2016: Journal of Cell Biology
Dante Cicchetti, Susan Hetzel, Fred A Rogosch, Elizabeth D Handley, Sheree L Toth
In the present investigation, differential methylation analyses of the whole genome were conducted among a sample of 548 school-aged low-income children (47.8% female, 67.7% Black, M age = 9.40 years), 54.4% of whom had a history of child maltreatment. In the context of a summer research camp, DNA samples via saliva were obtained. Using GenomeStudio, Methylation Module, and the Illumina Custom Model, differential methylation analyses revealed a pattern of greater methylation at low methylation sites (n = 197 sites) and medium methylation sites (n = 730 sites) and less methylation at high methylation sites (n = 907 sites) among maltreated children...
October 3, 2016: Development and Psychopathology
Haiyan Chu, Mary M McKenna, Nathan A Krump, Suilan Zheng, Laurel Mendelsohn, Swee Lay Thein, Lisa J Garrett, David M Bodine, Philip S Low
Functional studies have shown that the oxygenation state of the erythrocyte regulates many important pathways, including glucose metabolism, membrane mechanical stability and cellular ATP release. Deoxyhemoglobin, but not oxyhemoglobin, binds avidly and reversibly to band 3, the major erythrocyte membrane protein. Because band 3 associates with multiple metabolic, solute transport, signal transduction and structural proteins, the hypothesis naturally arises that the O2-dependent regulation of erythrocyte properties might be mediated by the reversible association of deoxyHb with band 3...
September 29, 2016: Blood
Hong Wei, Hai-Yun Wu, Zuyue Chen, Ai-Niu Ma, Xiao-Fang Mao, Teng-Fei Li, Xin-Yan Li, Yong-Xiang Wang, Antti Pertovaara
Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by d-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH)...
September 24, 2016: Pharmacology, Biochemistry, and Behavior
Kuei-Chun Wang, Yi-Ting Yeh, Phu Nguyen, Elaine Limqueco, Jocelyn Lopez, Satenick Thorossian, Kun-Liang Guan, Yi-Shuan J Li, Shu Chien
The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Wanwan He, Nengyan Fang, Ruisen Wang, Yunyu Wu, Guoying Zeng, Changhong Guan, Hao Chen, Ji Huang, Jianfei Wang, Yongmei Bao, Hongsheng Zhang
Heikezijing, a japonica rice landrace from Taihu region of China, exhibited broad-spectrum resistance to more than 300 isolates of the blast (Magnaporthe oryzae). In our previous research, we fine mapped a broad-spectrum resistance gene Pi-hk1 in chromosome 11. In this research, 2010-9(G1), one of the predominant race of the blast in Taihu Lake region of China, was inoculated into 162 recombinant inbred lines (RILs) and two parents Heikezijing and Suyunuo for mapping the resistance-blast quantitative trait loci (QTLs)...
September 27, 2016: Phytopathology
Karen Low, Tazeen Ashraf, Natalie Canham, Jill Clayton-Smith, Charu Deshpande, Alan Donaldson, Richard Fisher, Frances Flinter, Nicola Foulds, Alan Fryer, Kate Gibson, Ian Hayes, Alison Hills, Susan Holder, Melita Irving, Shelagh Joss, Emma Kivuva, Kathryn Lachlan, Alex Magee, Vivienne McConnell, Meriel McEntagart, Kay Metcalfe, Tara Montgomery, Ruth Newbury-Ecob, Fiona Stewart, Peter Turnpenny, Julie Vogt, David Fitzpatrick, Maggie Williams, Sarah Smithson
KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat-containing cofactors. We describe 32 KBG patients aged 2-47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent...
November 2016: American Journal of Medical Genetics. Part A
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