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https://www.readbyqxmd.com/read/29150643/%C3%AE-eudesmol-an-oxygenized-sesquiterpene-stimulates-appetite-via-trpa1-and-the-autonomic-nervous-system
#1
Kazuaki Ohara, Takafumi Fukuda, Yuko Ishida, Chika Takahashi, Rena Ohya, Mikio Katayama, Kunitoshi Uchida, Makoto Tominaga, Katsuya Nagai
Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149168/airway-expression-of-transient-receptor-potential-trp-vanniloid-1-and-ankyrin-1-channels-is-not-increased-in-patients-with-idiopathic-pulmonary-fibrosis
#2
Nicola-Xan Hutchinson, Allen Gibbs, Amanda Tonks, Benjamin D Hope-Gill
Dry cough is a common symptom described in patients with Idiopathic Pulmonary Fibrosis (IPF) and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however evidence suggests altered cough neurophysiology and sensitisation plays a role; IPF patients have an enhanced cough reflex sensitivity to inhaled capsaicin. The Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed...
2017: PloS One
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#3
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29133412/cell-autonomous-adiposity-through-increased-cell-surface-glut4-due-to-ankyrin-b-deficiency
#4
Damaris N Lorenzo, Vann Bennett
Obesity typically is linked to caloric imbalance as a result of overnutrition. Here we propose a cell-autonomous mechanism for adiposity as a result of persistent cell surface glucose transporter type 4 (GLUT4) in adipocytes resulting from impaired function of ankyrin-B (AnkB) in coupling GLUT4 to clathrin-mediated endocytosis. Adipose tissue-specific AnkB-KO mice develop obesity and progressive pancreatic islet dysfunction with age or high-fat diet (HFD). AnkB-deficient adipocytes exhibit increased lipid accumulation associated with increased glucose uptake and impaired endocytosis of GLUT4...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29128512/the-role-of-%C3%AE-ii-spectrin-in-cardiac-health-and-disease
#5
REVIEW
Mohamed H Derbala, Aaron S Guo, Peter J Mohler, Sakima A Smith
Spectrins are large, flexible proteins comprised of α-β dimers that are connected head-to-head to form the canonical heterotetrameric spectrin structure. Spectrins were initially believed to be exclusively found in human erythrocytic membrane and are highly conserved among different species. βII spectrin, the most common isoform of non-erythrocytic spectrin, is found in all nucleated cells and forms larger macromolecular complexes with ankyrins and actins. Not only is βII spectrin a central cytoskeletal scaffolding protein involved in preserving cell structure but it has also emerged as a critical protein required for distinct physiologic functions such as posttranslational localization of crucial membrane proteins and signal transduction...
November 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/29126898/structural-basis-for-the-selective-inhibition-of-c-jun-n-terminal-kinase-1-determined-by-rigid-darpin-darpin-fusions
#6
Yufan Wu, Annemarie Honegger, Alexander Batyuk, Peer R E Mittl, Andreas Plückthun
To untangle the complex signaling of the c-Jun N-terminal kinase (JNK) isoforms we need tools which can selectively detect and inhibit individual isoforms. Because of the high similarity between JNK1, JNK2 and JNK3, it is very difficult to generate small-molecule inhibitors with this discriminatory power. Thus, we have recently selected protein binders from the designed ankyrin repeat protein (DARPin) library which were indeed isoform-specific inhibitors of JNK1 with low nanomolar potency. Here we provide the structural basis for their isotype discrimination and their inhibitory action...
November 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29123523/identification-of-an-evolutionarily-conserved-ankyrin-domain-containing-protein-caiap-which-regulates-inflammasome-dependent-resistance-to-bacterial-infection
#7
Sylwia D Tyrkalska, Sergio Candel, Ana B Pérez-Oliva, Ana Valera, Francisca Alcaraz-Pérez, Diana García-Moreno, María L Cayuela, Victoriano Mulero
Many proteins contain tandemly repeated modules of several amino acids, which act as the building blocks that form the underlying architecture of a specific protein-binding interface. Among these motifs and one of the most frequently observed is ankyrin repeats (ANK), which consist of 33 amino acid residues that are highly conserved. ANK domains span a wide range of functions, including protein-protein interactions, such as the recruitment of substrate to the catalytic domain of an enzyme, or the assembly of stable multiprotein complexes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29121345/early-postnatal-exposure-to-airborne-fine-particulate-matter-induces-autism-like-phenotypes-in-male-rats
#8
Kang Li, Li Li, Bo Cui, Zhihui Gai, Qiuyue Li, Shumei Wang, Jun Yan, Bencheng Lin, Lei Tian, Huanliang Liu, Xiaohua Liu, Zhuge Xi
Epidemiological studies have revealed that ambient fine particulate matter (PM2.5) exposure is closely associated with autism spectrum disorder (ASD). However, there is a relative paucity of laboratory data to support this epidemic finding. In order to assess the relationship between PM2.5 exposure and ASD, neonatal male Sprague-Dawley (SD) rats were chosen and exposed to PM2.5 (2 or 20 mg/kg body weight, once a day) by intranasal instillation from postnatal day (PND) 8 to 22. It was found that when exposed to PM2...
November 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29121340/hace1-is-essential-for-astrocyte-mitochondrial-function-and-influences-huntington-disease-phenotypes-in-vivo
#9
Dagmar E Ehrnhoefer, Amber L Southwell, Meenalochani Sivasubramanian, Xiaofan Qiu, Erika B Villanueva, Yuanyun Xie, Sabine Waltl, Lisa Anderson, Anita Fazeli, Lorenzo Casal, Boguslaw Felczak, Michelle Tsang, Michael R Hayden
Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of HACE1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. HACE1 promotes the stability of Nrf2 and thus plays an important role in antioxidant response mechanisms, which are dysfunctional in HD. Moreover, HACE1 overexpression mitigates mutant huntingtin-induced oxidative stress in vitro through promotion of the Nrf2 antioxidant response...
November 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29114087/the-cooling-compound-icilin-attenuates-autoimmune-neuroinflammation-through-modulation-of-the-t-cell-response
#10
Benjamin W Ewanchuk, Euan R O Allan, Amy L Warren, Rithwik Ramachandran, Robin M Yates
The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti-inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)-a CD4(+) T cell-driven murine model of MS-we found that both wild-type (WT) and TRPM8-deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation...
November 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29110513/ankaferd-influences-mrna-expression-of-iron-regulated-genes-during-iron-deficiency-anemia
#11
Afife Gulec, Sukru Gulec
Ankaferd Blood Stopper (ABS) comprises a mixture of plants and stops bleeding via forming a protein network by erythroid aggregation. Bleeding causes reduction of iron levels in body. It has been indicated that ABS contains significant amount of iron. Thus, we investigated the biological activity of ABS-derived iron on iron-regulated genes during iron-deficiency anemia (IDA). IDA We selected Caco-2 and HepG2 cell lines as in vitro models of human intestine and liver, respectively. Iron deficiency anemia was induced by deferoxamine...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29109270/m-current-inhibition-rapidly-induces-a-unique-ck2-dependent-plasticity-of-the-axon-initial-segment
#12
Jonathan Lezmy, Maya Lipinsky, Yana Khrapunsky, Eti Patrich, Lia Shalom, Asher Peretz, Ilya A Fleidervish, Bernard Attali
Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-type K(+) channels, which predominantly localize to the AIS and are essential for tuning neuronal excitability. While acute M-current inhibition via cholinergic activation or direct channel block made neurons more excitable, minutes to hours of sustained M-current depression resulted in a gradual reduction in intrinsic excitability...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29109170/l1-coupling-to-ankyrin-and-the-spectrin-actin-cytoskeleton-modulates-ethanol-inhibition-of-l1-adhesion-and-ethanol-teratogenesis
#13
Xiaowei Dou, Carrie Menkari, Rei Mitsuyama, Tatiana Foroud, Leah Wetherill, Peter Hammond, Michael Suttie, Xiaopan Chen, Shao-Yu Chen, Michael E Charness
Ethanol causes fetal alcohol spectrum disorders (FASD) partly by inhibiting cell adhesion mediated by the L1 neural cell adhesion molecule. Ethanol interacts with an alcohol binding pocket in the L1 extracellular domain (ECD), and dephosphorylation of S1248 in the L1 cytoplasmic domain (CD) renders L1 adhesion insensitive to inhibition by ethanol (L1 insensitive). The mechanism underlying this inside-out signaling is unknown. Here we show that phosphorylation of the human L1-CD at S1152, Y1176, S1181, and S1248 renders L1 sensitive to ethanol by promoting L1 coupling with ankyrin-G and the spectrin-actin cytoskeleton...
November 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29103325/myofibrillogenesis-regulator-1-mr-1-a-potential-therapeutic-target-for-cancer-and-pnkd
#14
Junxia Wang, Wuli Zhao, Hong Liu, Hongwei He, Rongguang Shao
Human myofibrillogenesis regulator 1 (MR-1) is a functional gene also known as paroxysmal nonkinesigenic dyskinesia (PNKD). It is localized on human chromosome 2q35, and three different isomers, MR-1L, MR-1M, and MR-1S, are formed by alternative splicing. MR-1S promotes cardiac hypertrophy and is closely related to cancer. MR-1S is overexpressed in hematologic and solid malignancies, such as hepatoma, breast cancer, and chronic myelogenous leukemia. MR-1S causes disordered cell differentiation, initiates malignant transformation and accelerates metastasis...
November 6, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29101090/a-biosynthetic-route-for-polysialylating-proteins-in-escherichia-coli
#15
Timothy G Keys, Michael Wetter, Ivan Hang, Christoph Rutschmann, Simona Russo, Manuela Mally, Michael Steffen, Matthias Zuppiger, Fabian Müller, Jörg Schneider, Amirreza Faridmoayer, Chia-Wei Lin, Markus Aebi
Polysialic acid (polySia) is a posttranslational modification found on only a handful of proteins in the central nervous and immune systems. The addition of polySia to therapeutic proteins improves pharmacokinetics and reduces immunogenicity. To date, polysialylation of therapeutic proteins has only been achieved in vitro by chemical or chemoenzymatic strategies. In this work, we develop a biosynthetic pathway for site-specific polysialylation of recombinant proteins in the cytoplasm of Escherichia coli. The pathway takes advantage of a bacterial cytoplasmic polypeptide-glycosyltransferase to establish a site-specific primer on the target protein...
November 1, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29099659/identification-of-a-de-novo-ank1-mutation-in-a-chinese-family-with-hereditary-spherocytosis
#16
Hongzai Guan, Xinping Liang, Rong Zhang, Haiyan Wang, Wenmiao Liu, Ru Zhang, Jie Yang, Shiguo Liu
OBJECTIVES: Hereditary spherocytosis (HS) is a genetic heterogeneous disorder characterized by sphere-shaped erythrocytes on peripheral blood smear with a few clinical manifestations. As an important red cell membrane protein, ankyrin 1 can interact with transmembrane proteins and the membrane skeleton and mutations in the ankyrin 1 (ANK1) genes affect about half of all patients with HS. The purpose of this study was to investigate a Chinese Han family with HS to find out the causative gene mutation and explore the genotype-phenotype correlation which can provide the basis for the pathogenesis and prenatal diagnosis for this disease...
November 3, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#17
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29094334/quantitative-mass-spectrometry-of-human-reticulocytes-reveal-proteome-wide-modifications-during-maturation
#18
Trang T T Chu, Ameya Sinha, Benoit Malleret, Rossarin Suwanarusk, Jung E Park, Renugah Naidu, Rupambika Das, Bamaprasad Dutta, Seow Theng Ong, Navin K Verma, Jerry K Chan, François Nosten, Laurent Rénia, Siu K Sze, Bruce Russell, Rajesh Chandramohanadas
Erythropoiesis is marked by progressive changes in morphological, biochemical and mechanical properties of erythroid precursors to generate red blood cells (RBC). The earliest enucleated forms derived in this process, known as reticulocytes, are multi-lobular and spherical. As reticulocytes mature, they undergo a series of dynamic cytoskeletal re-arrangements and the expulsion of residual organelles, resulting in highly deformable biconcave RBCs (normocytes). To understand the significant, yet neglected proteome-wide changes associated with reticulocyte maturation, we undertook a quantitative proteomics approach...
November 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29084244/trpa1-activation-in-peripheral-sensory-neurons-underlies-the-ionic-basis-of-pain-hypersensitivity-in-response-to-vinca-alkaloids
#19
Nina Boiko, Geraldo Medrano, Elizabeth Montano, Nan Jiang, Claire R Williams, Ngonidzashe B Madungwe, Jean C Bopassa, Charles C Kim, Jay Z Parrish, Kenneth M Hargreaves, James D Stockand, Benjamin A Eaton
Chemotherapy induced peripheral neuropathy (CIPN), a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described...
2017: PloS One
https://www.readbyqxmd.com/read/29081457/an-aliphatic-ester-diisopropyl-sebacate-exhibited-an-adjuvant-effect-on-fluorescein-isothiocyanate-induced-contact-hypersensitivity-mouse-models
#20
Kohta Kurohane, Ayako Kimura, Rie Terasawa, Kamiyu Kobayashi, Wakana Suzuki, Takeshi Matsuoka, Yasuyuki Imai
Alternative plasticizers have become more popular due to health concerns about phthalate esters. We demonstrated that phthalate esters enhanced skin sensitization to fluorescein isothiocyanate (FITC) in mouse contact hypersensitivity models. Alternative plasticizers have not been well studied as to their effect on the immune system. We previously found that diisopropyl adipate (DIPA), an aliphatic dicarboxylic acid ester, enhanced skin sensitization to FITC. Sebacate esters are also widely used as alternative plasticizers...
October 27, 2017: Biological & Pharmaceutical Bulletin
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