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https://www.readbyqxmd.com/read/28225032/4-isopropylcyclohexanol-has-potential-analgesic-effects-through-the-inhibition-of-anoctamin-1-trpv1-and-trpa1-channel-activities
#1
Yasunori Takayama, Hidemasa Furue, Makoto Tominaga
Interactions between calcium-activated chloride channel anoctamin 1 (ANO1) and transient receptor potential vanilloid 1 (TRPV1) enhance pain sensations in mice, suggesting that ANO1 inhibition could have analgesic effects. Here we show that menthol and the menthol analogue isopropylcyclohexane (iPr-CyH) inhibited ANO1 channels in mice. The iPr-CyH derivative 4-isopropylcyclohexanol (4-iPr-CyH-OH) inhibited mouse ANO1 currents more potently than iPr-CyH. Moreover, 4-iPr-CyH-OH inhibited the activities of TRPV1, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8) and TRPV4...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220825/notch1-promoted-trpa1-expression-in-erythroleukemic-cells-suppresses-erythroid-but-enhances-megakaryocyte-differentiation
#2
Ji-Lin Chen, Yueh-Hsin Ping, Min-Jen Tseng, Yuan-I Chang, Hsin-Chen Lee, Rong-Hong Hsieh, Tien-Shun Yeh
The Notch1 pathway plays important roles in modulating erythroid and megakaryocyte differentiation. To screen the Notch1-related genes that regulate differentiation fate of K562 and HEL cells, the expression of transient receptor potential ankyrin 1 (TRPA1) was induced by Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor. N1IC and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1) bound to TRPA1 promoter region to regulate transcription in K562 cells. Transactivation of TRPA1 promoter by N1IC depended on the methylation status of TRPA1 promoter...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#3
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28207739/overexpression-of-notch-regulated-ankyrin-repeat-protein-is-associated-with-papillary-thyroid-carcinoma-progression
#4
Mingdi Zhang, Yiyu Qin, Bin Zuo, Wei Gong, Shenglai Zhang, Yurong Gong, Zhiwei Quan, Bingfeng Chu
Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28199072/genetic-risk-score-analysis-in-early-onset-bipolar-disorder
#5
Paul E Croarkin, Joan L Luby, Kelly Cercy, Jennifer R Geske, Marin Veldic, Matthew Simonson, Paramjit T Joshi, Karen Dineen Wagner, John T Walkup, Malik M Nassan, Alfredo B Cuellar-Barboza, Leah Casuto, Susan L McElroy, Peter S Jensen, Mark A Frye, Joanna M Biernacka
OBJECTIVE: In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS: Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria...
February 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28197074/the-first-extracellular-linker-is-important-for-several-aspects-of-the-gating-mechanism-of-human-trpa1-channel
#6
Lenka Marsakova, Ivan Barvik, Vlastimil Zima, Lucie Zimova, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28196903/ankyrin-b-defects-serendipity-and-inquisitiveness-are-the-mothers-of-invention
#7
EDITORIAL
Henry Duff, Robert S Sheldon
No abstract text is available yet for this article.
January 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28196901/novel-variant-in-the-ank2-membrane-binding-domain-is-associated-with-ankyrin-b-syndrome-and-structural-heart-disease-in-a-first-nations-population-with-a-high-rate-of-long-qt-syndrome
#8
Leigh Anne Swayne, Nathaniel P Murphy, Sirisha Asuri, Lena Chen, Xiaoxue Xu, Sarah McIntosh, Chao Wang, Peter J Lancione, Jason D Roberts, Charles Kerr, Shubhayan Sanatani, Elizabeth Sherwin, Crystal F Kline, Mingjie Zhang, Peter J Mohler, Laura T Arbour
BACKGROUND: Long QT syndrome confers susceptibility to ventricular arrhythmia, predisposing to syncope, seizures, and sudden death. While rare globally, long QT syndrome is ≈15× more common in First Nations of Northern British Columbia largely because of a known mutation in KCNQ1. However, 2 large multigenerational families were affected, but negative for the known mutation. METHODS AND RESULTS: Long QT syndrome panel testing was carried out in the index case of each family, and clinical information was collected...
January 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28194754/requirement-of-extracellular-ca-2-binding-to-specific-amino-acids-for-heat-evoked-activation-of-trpa1
#9
Erkin Kurganov, Shigeru Saito, Claire T Saito, Makoto Tominaga
Transient receptor potential ankyrin 1 (TRPA1) is a homotetrameric nonselective cation-permeable channel that has six transmembrane domains and cytoplasmic N- and C-termini. The N-terminus is characterized by an unusually large number of ankyrin repeats. Although the 3-dimensional structure of human TRPA1 has been determined, and TRPA1 channels from insects to birds are known to be activated by heat stimulus, the mechanism for temperature-dependent TRPA1 activation is unclear. We previously reported that extracellular Ca(2+) , but not intracellular Ca(2+) , plays an important role in heat-evoked TRPA1 activation in green anole lizards (gaTRPA1)...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28187360/de-novo-assembly-of-the-ringed-seal-pusa-hispida-blubber-transcriptome-a-tool-that-enables-identification-of-molecular-health-indicators-associated-with-pcb-exposure
#10
Tanya M Brown, S Austin Hammond, Bahar Behsaz, Nik Veldhoen, Inanç Birol, Caren C Helbing
The ringed seal, Pusa hispida, is a keystone species in the Arctic marine ecosystem, and is proving a useful marine mammal for linking polychlorinated biphenyl (PCB) exposure to toxic injury. We report here the first de novo assembled transcriptome for the ringed seal (342,863 transcripts, of which 53% were annotated), which we then applied to a population of ringed seals exposed to a local PCB source in Arctic Labrador, Canada. We found an indication of energy metabolism imbalance in local ringed seals (n=4), and identified five significant gene transcript targets: plasminogen receptor (Plg-R(KT)), solute carrier family 25 member 43 receptor (Slc25a43), ankyrin repeat domain-containing protein 26-like receptor (Ankrd26), HIS30 (not yet annotated) and HIS16 (not yet annotated) that may represent indicators of PCB exposure and effects in marine mammals...
February 3, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28184187/ankyrin-g-membrane-partners-drive-the-establishment-and-maintenance-of-the-axon-initial-segment
#11
Christophe Leterrier, Nadine Clerc, Fanny Rueda-Boroni, Audrey Montersino, Bénédicte Dargent, Francis Castets
The axon initial segment (AIS) is a highly specialized neuronal compartment that plays a key role in neuronal development and excitability. It concentrates multiple membrane proteins such as ion channels and cell adhesion molecules (CAMs) that are recruited to the AIS by the scaffold protein ankyrin G (ankG). The crucial function of ankG in the anchoring of AIS membrane components is well established, but a reciprocal role of membrane partners in ankG targeting and stabilization remained elusive. In rat cultured hippocampal neurons and cortical organotypic slices, we found that shRNA-mediated knockdown of ankG membrane partners (voltage-gated sodium channels (Nav) or neurofascin-186) led to a decrease of ankG concentration and perturbed the AIS formation and maintenance...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28182310/ankyrin-rich-membrane-spanning-protein-as-a-novel-modulator-of-transient-receptor-potential-vanilloid-1-function-in-nociceptive-neurons
#12
J Peter, C Kasper, M Kaufholz, R Buschow, J Isensee, T Hucho, F W Herberg, F Schwede, C Stein, S-E Jordt, M Brackmann, V Spahn
BACKGROUND: The ion channel TRPV1 is mainly expressed in small diameter dorsal root ganglion (DRG) neurons, which are involved in the sensation of acute noxious thermal and chemical stimuli. Direct modifications of the channel by diverse signalling events have been intensively investigated, but little is known about the composition of modulating macromolecular TRPV1 signalling complexes. Here, we hypothesize that the novel adaptor protein ankyrin-rich membrane spanning protein/kinase D interacting substrate (ARMS) interacts with TRPV1 and modulates its function in rodent DRG neurons...
February 9, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28181483/nf-%C3%AE%C2%BAb-regulates-neuronal-ankyrin-g-via-a-negative-feedback-loop
#13
Hans-Georg König, Robert Schwamborn, Silke Andresen, Sinéad Kinsella, Orla Watters, Beau Fenner, Jochen H M Prehn
The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179641/shank-proteins-roles-at-the-synapse-and-in-autism-spectrum-disorder
#14
REVIEW
Patricia Monteiro, Guoping Feng
Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour...
March 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28176353/lysophosphatidic-acid-induced-itch-is-mediated-by-signaling-of-lpa5-receptor-phospholipase-d-and-trpa1-trpv1
#15
Hiroki Kittaka, Kunitoshi Uchida, Naomi Fukuta, Makoto Tominaga
Intractable and continuous itch sensations often accompany diseases such as atopic dermatitis, neurogenic lesions, uremia and cholestasis. Lysophosphatidic acid (LPA) is an itch mediator found in cholestatic itch patients and it induces acute itch and pain in the experimental rodent models. However, the molecular mechanism by which LPA activates peripheral sensory neurons remains unknown. In this study, we used a cheek injection method in mice to reveal that LPA induced itch-related behaviors but not pain-related behaviors...
February 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28163384/association-between-alcohol-induced-erythrocyte-membrane-alterations-and-hemolysis-in-chronic-alcoholics
#16
Saradamma Bulle, Vaddi Damodara Reddy, Pannuru Padmavathi, Paramahamsa Maturu, Pavan Kumar Puvvada, Varadacharyulu Nallanchakravarthula
The present study aimed to understand the association between erythrocyte membrane alterations and hemolysis in chronic alcoholics. Study was conducted on human male volunteers aged between 35-45 years with a drinking history of 8-10 years. Results showed that plasma marker enzymes AST, ALT, ALP and γGT were increased in alcoholic subjects. Plasma and erythrocyte membrane lipid peroxidation, erythrocyte lysate nitric oxide (NOx) levels were also increased significantly in alcoholics. Furthermore, erythrocyte membrane protein carbonyls, total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio were increased in alcoholics...
January 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28160493/analysis-of-transcriptional-responses-of-normalizing-genes-on-crassostrea-brasiliana-under-different-experimental-conditions
#17
Gabrielle do Amaral E Silva Müller, Daína de Lima, Flávia Lucena Zacchi, Rômi Sharon Piazza, Karim Hahn Lüchmann, Jacó Joaquim Mattos, Daniel Schlenk, Afonso Celso Dias Bainy
Bivalves show remarkable plasticity to environmental changes and have been proposed as sentinel organisms in biomonitoring. Studies related to transcriptional analysis using quantitative real-time PCR (qRT-PCR) in these organisms have notably increased, imposing a need to identify and validate adequate reference genes for an accurate and reliable analysis. In the present study, nine reference genes were selected from transcriptome data of Crassostrea brasiliana in order to identify their suitability as qRT-PCR normalizer genes...
February 4, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28148727/early-and-late-loss-of-the-cytoskeletal-scaffolding-protein-ankyrin-g-reveals-its-role-in-maturation-and-maintenance-of-nodes-of-ranvier-in-myelinated-axons
#18
Julia Saifetiarova, Anna M Taylor, Manzoor A Bhat
: The mechanisms that govern node of Ranvier organization, stability and long-term maintenance remain to be fully elucidated. One of the molecular components of the node is the cytoskeletal scaffolding protein, Ankyrin G (AnkG), which interacts with multiple members of the nodal complex. The role of AnkG in nodal organization and maintenance is still not clearly defined, as to whether AnkG functions as an initial nodal organizer or whether it functions as a nodal stabilizer after the nodal complex has been assembled...
February 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28134789/mrpl10-and-tbp-are-suitable-reference-genes-for-peripheral-nerve-crush-injury
#19
Yaxian Wang, Qianqian Shan, Yali Meng, Jiacheng Pan, Sheng Yi
Peripheral nerve injury triggers the dysregulation of a large number of genes at multiple sites, including neurons, peripheral nerve stump, and the target organ. Housekeeping genes were frequently used as reference genes to normalize the expression values of target genes. Suitable selection of housekeeping genes that are stably expressed after nerve injury minimizes bias elicited by reference genes and thus helps to better and more sensitively reflect gene expression changes. However, many housekeeping genes have been used as reference genes without testing the expression patterns of themselves...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28123587/analysis-of-molecular-markers-as-predictive-factors-of-lymph-node-involvement-in-breast-carcinoma
#20
Luciana Marques Paula, Luis Henrique Ferreira De Moraes, Abaeté Leite Do Canto, Laurita Dos Santos, Airton Abrahão Martin, Silvia Regina Rogatto, Renata De Azevedo Canevari
Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer...
January 2017: Oncology Letters
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