First Survey and Functional Annotation of Prohormone and Convertase
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Human Recombinant H2 Relaxin Induces AKT and Gsk3β Phosphorylation and HTR-8/Svneo Cell Proliferation
Kobe J. Med. Sci., Vol. 61, No. 1, pp. E1-E8, 2015 Human Recombinant H2 Relaxin Induces AKT and GSK3β Phosphorylation and HTR-8/SVneo Cell Proliferation YONI ASTUTI 1.2, KOJI NAKABAYASHI 1, MASASHI DEGUCHI 1, YASUHIKO EBINA 1, and HIDETO YAMADA 1 1 Department of Obstetric Gynaecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan 2 Faculty of Medicine and Health Science, University Muhammadiyah Yogyakarta, Bantul 55183, Indonesia Received 9 December 2014/ Accepted 19 January 2015 Keywords: rH2 relaxin, pAKT/AKT, pGSK3β /GSK3β, proliferation ABSTRACT Relaxin is essential for trophoblast development during pregnancy. Evidence shows that relaxin increases trophoblast cell migration capacity. Here, we show the effect of relaxin on protein kinase B (AKT) activation and glycogen synthase kinase 3-beta (GSK3β) inactivation as well as on the proliferation of HTR-8/SVneo cells, a model of human extravillous trophoblast (EVT). HTR-8/SVneo cells were treated with different doses of human recombinant (rH2) relaxin in serum- deprived conditions and treated for increasing time with 1 ng/mL of rH2 relaxin. Western blot analysis was performed to detect pAKT, AKT, pGSK3β, GSK3β, and actin expression. Proliferation of HTR- 8/SVneo cells was analyzed by MTS assay. rH2 relaxin treatment increased the ratio of pAKT/AKT, pGSK3β/GSK3β, and proliferation in HTR- 8/SVneo cells. Furthermore, AKT and GSK3β activation by rH2 relaxin was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor. This study suggests that rH2 relaxin induces AKT and GSK3β phosphorylation as well as proliferation in HTR-8/SVneo cells. -
Calcitonin Gene Products and the Kidney
Kiinische Klin Wochenschr (1989) 67:870-875 W°chenchrif t © Springer-Verlag 1989 Calcitonin Gene Products and the Kidney A. Kurtz 1, R. Muff z, and J.A. Fischer z 1 Physiologic Institute, University of Ziirich, Switzerland 2 Research Laboratory for Calcium Metabolism, Departments of Orthopedic Surgery and Medicine, University of Ziirich, Ziirich, Switzerland Summary. Calcitonin gene-related peptide (CGRP) Calcitonin and CGRP are single chain polypep- is localized in capsaicin-sensitive nerve fibres in the tides consisting of 32 and 37 amino acids, respec- kidney and urogenital tract whereas calcitonin tively. They have in common amino-terminal ring reaches the kidney through the general circulation. structures linked by disulfide bridges and the car- Systemic infusion of CGRP and perfusion of iso- boxyltermini are amidated. In man, CGRP shares lated rat kidney reduces vascular resistance, and 16% structural homology with calcitonin whereas increases renal blood flow and glomerular filtra- the homology between CGRP-I and -II is 92% tion. CGRP stimulates renin secretion in vivo and [13]. As a result, distinct receptors for calcitonin in vitro and inhibits contraction of isolated rat me- and CGRP have been identified [7, 11, 33, 42]. sangial cells by angiotensin II. Calcitonin does not Human CGRP-I and -II, due to their high homolo- affect vascular resistance, renal blood flow and glo- gy, crossreact almost completely, but subtle differ- merular filtration, and is tess potent in stimulating ences in the distribution of human CGRP-I and renin secretion, and does not alter contraction of -II binding sites have been observed on receptor isolated rat mesangial cells by angiotensin II. -
Differential Gene Expression Profile in Endometrioid And
[CANCER RESEARCH 63, 5697–5702, September 15, 2003] Advances in Brief Differential Gene Expression Profile in Endometrioid and Nonendometrioid Endometrial Carcinoma: STK15 Is Frequently Overexpressed and Amplified in Nonendometrioid Carcinomas1 Gema Moreno-Bueno, Carolina Sa´nchez-Este´vez, Rau´l Cassia, Sandra Rodrı´guez-Perales, Ramo´n Dı´az-Uriarte, Orlando Domı´nguez, David Hardisson, Miguel Andujar, Jaime Prat, Xavier Matias-Guiu, Juan C. Cigudosa, and Jose´Palacios2 Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme [G. M-B., C. S-E., R. C., J. Pa.] and Biotechnology Programme [S. R-P., R. D-U., O. D., J. C. C.], Centro Nacional de Investigaciones Oncologicas, Madrid; Department of Pathology, Hospital Universitario La Paz, Madrid [D. H.]; Department of Pathology, Hospital Materno Infantil, Las Palmas [M. A.]; Department of Pathology, Hospital Sant Pau y Sant Creu, Barcelona [J. Pr.]; and Department of Pathology, Hospital Arnau de Villanova, Lleida [X. M-G.], Spain Abstract tiated endometrioid carcinomas that usually develop in pre- and perimenopausal women. They are associated with estrogen stimula- Endometrial carcinoma (EC) comprises at least two types of cancer: tion, coexist with, or are preceded by atypical endometrial hyperplasia endometrioid carcinomas (EECs) are estrogen-related tumors, which are and are associated with ER positivity and with K-RAS, PTEN, and frequently euploid and have a good prognosis. Nonendometrioid carcino-  mas (NEECs; serous and clear cell forms) are not estrogen related, are -catenin mutations, and microsatellite instability. Conversely, type II frequently aneuploid, and are clinically aggressive. We used cDNA mi- tumors are NEECs (papillary serous and clear cell carcinomas) that croarrays containing 6386 different genes to analyze gene expression occur in older women. -
Cellular Responses to Erbb-2 Overexpression in Human Mammary Luminal Epithelial Cells: Comparison of Mrna and Protein Expression
British Journal of Cancer (2004) 90, 173 – 181 & 2004 Cancer Research UK All rights reserved 0007 – 0920/04 $25.00 www.bjcancer.com Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression SL White1, S Gharbi1, MF Bertani1, H-L Chan1, MD Waterfield1 and JF Timms*,1 1 Ludwig Institute for Cancer Research, Wing 1.1, Cruciform Building, Gower Street, London WCIE 6BT, UK Microarray analysis offers a powerful tool for studying the mechanisms of cellular transformation, although the correlation between mRNA and protein expression is largely unknown. In this study, a microarray analysis was performed to compare transcription in response to overexpression of the ErbB-2 receptor tyrosine kinase in a model mammary luminal epithelial cell system, and in response to the ErbB-specific growth factor heregulin b1. We sought to validate mRNA changes by monitoring changes at the protein level using a parallel proteomics strategy, and report a surprisingly high correlation between transcription and translation for the subset of genes studied. We further characterised the identified targets and relate differential expression to changes in the biological properties of ErbB-2-overexpressing cells. We found differential regulation of several key cell cycle modulators, including cyclin D2, and downregulation of a large number of interferon-inducible genes, consistent with increased proliferation of the ErbB-2- overexpressing cells. Furthermore, differential expression of genes involved in extracellular matrix modelling and cellular adhesion was linked to altered adhesion of these cells. Finally, we provide evidence for enhanced autocrine activation of MAPK signalling and the AP-1 transcription complex. -
Mechanical Forces Induce an Asthma Gene Signature in Healthy Airway Epithelial Cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T
www.nature.com/scientificreports OPEN Mechanical forces induce an asthma gene signature in healthy airway epithelial cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T. Kho4, Kelan Tantisira1, Marc Santolini 1,5, Feixiong Cheng6,7,8, Jennifer A. Mitchel3, Maureen McGill3, Michael J. O’Sullivan3, Margherita De Marzio1,3, Amitabh Sharma1, Scott H. Randell9, Jefrey M. Drazen3, Jefrey J. Fredberg3 & Scott T. Weiss1,3* Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufcient to induce infammatory, late repair, and fbrotic pathways. Remarkably, this molecular profle of non-asthmatic cells after compression recapitulated the profle of asthmatic cells before compression. Together, these results show that even in the absence of any infammatory stimulus, mechanical compression alone is sufcient to induce an asthma-like molecular signature. Bronchial epithelial cells (BECs) form a physical barrier that protects pulmonary airways from inhaled irritants and invading pathogens1,2. Moreover, environmental stimuli such as allergens, pollutants and viruses can induce constriction of the airways3 and thereby expose the bronchial epithelium to compressive mechanical stress. In BECs, this compressive stress induces structural, biophysical, as well as molecular changes4,5, that interact with nearby mesenchyme6 to cause epithelial layer unjamming1, shedding of soluble factors, production of matrix proteins, and activation matrix modifying enzymes, which then act to coordinate infammatory and remodeling processes4,7–10. -
Neuromedin U Directly Stimulates Growth of Cultured Rat Calvarial Osteoblast-Like Cells Acting Via the NMU Receptor 2 Isoform
363-368 1/8/08 15:53 Page 363 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22: 363-368, 2008 363 Neuromedin U directly stimulates growth of cultured rat calvarial osteoblast-like cells acting via the NMU receptor 2 isoform MARCIN RUCINSKI, AGNIESZKA ZIOLKOWSKA, MARIANNA TYCZEWSKA, MARTA SZYSZKA and LUDWIK K. MALENDOWICZ Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecicki St., 60-781 Poznan, Poland Received April 4, 2008; Accepted June 2, 2008 DOI: 10.3892/ijmm_00000031 Abstract. The neuromedin U (NMU) system is composed of nervous system. Among others, peptides involved in regulation NMU, neuromedin S (NMS) and their receptors NMUR1 and of energy homeostasis belong to this group of compounds NMUR2. This system is involved in the regulation of energy (1-3), and the best recognised is leptin, an adipocyte-derived homeostasis, neuroendocrine functions, immune response, anorexigenic hormone, which plays a role in regulating bone circadian rhythm and spermatogenesis. The present study formation. Acting directly this pleiotropic cytokine exerts a aimed to investigate the possible role of the NMU system in stimulatory effect on bone formation. While acting through regulating functions of cultured rat calvarial osteoblast-like the central nervous system (CNS) leptin suppresses bone (ROB) cells. By using QPCR, high expression of NMU formation (4-10). Moreover, OB-Rb mRNA is expressed in mRNA was found in freshly isolated ROB cells while after 7, osteoblasts, and in vitro leptin enhances their proliferation 14, and 21 days of culture, expression of the studied gene and has no effect on osteocalcin and osteopontin production by was very low. -
Adipokines in Breast Milk: an Update Gönül Çatlı1, Nihal Olgaç Dündar2, Bumin Nuri Dündar3
J Clin Res Pediatr Endocrinol 2014;6(4):192-201 DO I: 10.4274/jcrpe.1531 Review Adipokines in Breast Milk: An Update Gönül Çatlı1, Nihal Olgaç Dündar2, Bumin Nuri Dündar3 1Tepecik Training and Research Hospital, Clinic of Pediatric Endocrinology, İzmir, Turkey 2Katip Çelebi University Faculty of Medicine, Department of Pediatric Neurology, İzmir, Turkey 3Katip Çelebi University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey Introduction Human breast milk comprises a variety of nutrients, cytokines, peptides, enzymes, cells, immunoglobulins, proteins and steroids specially suited to meet the needs of newborn infants (1,2). Breast milk has benefits on preventing metabolic disorders and chronic diseases and is referred to as “functional food” due to its roles other than nutrition (1,2). It contains 87-90% water and is the main source of water for newborns (3,4,5). In addition, several peptide/protein hormones have recently been identified in human breast milk, including leptin, adiponectin, resistin, obestatin, nesfatin, irisin, adropin, copeptin, ghrelin, pituitary adenylate cyclase-activating polypeptide, apelins, motilin and cholecystokinin (6,7). These breast milk hormones may transiently regulate the activities of various tissues, including endocrine organs until the endocrine system of the neonate begins to function (6). Some of these peptides are secreted in biologically active forms (3). Leptin, ghrelin, insulin, adiponectin, obestatin, resistin, epidermal growth factor, platelet-derived growth factor and insulin-like growth factor 1 are bioactive substances that play roles in energy intake and regulation of body composition (3). However, functions of some ABS TRACT of these peptides in neonatal development are still unknown Epidemiological surveys indicate that nutrition in infancy is implicated in the (4). -
CURRICULUM VITAE Joseph S. Takahashi Howard Hughes Medical
CURRICULUM VITAE Joseph S. Takahashi Howard Hughes Medical Institute Department of Neuroscience University of Texas Southwestern Medical Center 5323 Harry Hines Blvd., NA4.118 Dallas, Texas 75390-9111 (214) 648-1876, FAX (214) 648-1801 Email: [email protected] DATE OF BIRTH: December 16, 1951 NATIONALITY: U.S. Citizen by birth EDUCATION: 1981-1983 Pharmacology Research Associate Training Program, National Institute of General Medical Sciences, Laboratory of Clinical Sciences and Laboratory of Cell Biology, National Institutes of Health, Bethesda, MD 1979-1981 Ph.D., Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, Oregon, Dr. Michael Menaker, Advisor. Summer 1977 Hopkins Marine Station, Stanford University, Pacific Grove, California 1975-1979 Department of Zoology, University of Texas, Austin, Texas 1970-1974 B.A. in Biology, Swarthmore College, Swarthmore, Pennsylvania PROFESSIONAL EXPERIENCE: 2013-present Principal Investigator, Satellite, International Institute for Integrative Sleep Medicine, World Premier International Research Center Initiative, University of Tsukuba, Japan 2009-present Professor and Chair, Department of Neuroscience, UT Southwestern Medical Center 2009-present Loyd B. Sands Distinguished Chair in Neuroscience, UT Southwestern 2009-present Investigator, Howard Hughes Medical Institute, UT Southwestern 2009-present Professor Emeritus of Neurobiology and Physiology, and Walter and Mary Elizabeth Glass Professor Emeritus in the Life Sciences, Northwestern University -
Neurotensin Activates Gabaergic Interneurons in the Prefrontal Cortex
The Journal of Neuroscience, February 16, 2005 • 25(7):1629–1636 • 1629 Behavioral/Systems/Cognitive Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex Kimberly A. Petrie,1 Dennis Schmidt,1 Michael Bubser,1 Jim Fadel,1 Robert E. Carraway,2 and Ariel Y. Deutch1 1Departments of Pharmacology and Psychiatry, Vanderbilt University Medical Center, Nashville, Tennessee 37212, and 2Department of Physiology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655 Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We used in vivo microdialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administra- tion of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]tricyclo(3.3.1.1.3.7)decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. -
Supporting Online Material
1 2 3 4 5 6 7 Supplementary Information for 8 9 Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic 10 retinopathy 11 12 *Samuel A. Mills, *Andrew I. Jobling, *Michael A. Dixon, Bang V. Bui, Kirstan A. Vessey, Joanna A. Phipps, 13 Ursula Greferath, Gene Venables, Vickie H.Y. Wong, Connie H.Y. Wong, Zheng He, Flora Hui, James C. 14 Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher 15 * Joint first authors 16 17 Corresponding author: 18 Prof. Erica L. Fletcher. Department of Anatomy & Neuroscience. The University of Melbourne, Grattan St, 19 Parkville 3010, Victoria, Australia. 20 Email: [email protected] ; Tel: +61-3-8344-3218; Fax: +61-3-9347-5219 21 22 This PDF file includes: 23 24 Supplementary text 25 Figures S1 to S10 26 Tables S1 to S7 27 Legends for Movies S1 to S2 28 SI References 29 30 Other supplementary materials for this manuscript include the following: 31 32 Movies S1 to S2 33 34 35 36 1 1 Supplementary Information Text 2 Materials and Methods 3 Microglial process movement on retinal vessels 4 Dark agouti rats were anaesthetized, injected intraperitoneally with rhodamine B (Sigma-Aldrich) to label blood 5 vessels and retinal explants established as described in the main text. Retinal microglia were labelled with Iba-1 6 and imaging performed on an inverted confocal microscope (Leica SP5). Baseline images were taken for 10 7 minutes, followed by the addition of PBS (10 minutes) and then either fractalkine or fractalkine + candesartan 8 (10 minutes) using concentrations outlined in the main text. -
Hypothalamic Mechanisms Associated with Corticotropin-Releasing Factor- Induced Anorexia in Chicks T ⁎ Jinxin Wanga, Justin Matiasa, Elizabeth R
Neuropeptides 74 (2019) 95–102 Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep Hypothalamic mechanisms associated with corticotropin-releasing factor- induced anorexia in chicks T ⁎ Jinxin Wanga, Justin Matiasa, Elizabeth R. Gilberta,b, Tetsuya Tachibanac, Mark A. Clinea,b, a Department of Animal and Poultry Sciences, School of Neuroscience, USA b Virginia Polytechnic Institute and State University, Blacksburg 24061, VA, USA c Department of Agrobiological Science, Faculty of Agriculture, Ehime University, Matsuyama 790-8566, Japan ARTICLE INFO ABSTRACT Keywords: Central administration of corticotropin-releasing factor (CRF), a 41-amino acid peptide, is associated with potent Arcuate nucleus anorexigenic effects in rodents and chickens. However, the mechanism underlying this effect remains unclear. Chick Hence, the objective of the current study was to elucidate the hypothalamic mechanisms that mediate CRF- Corticotropin-releasing factor induced anorexia in 4 day-old Cobb-500 chicks. After intracerebroventricular (ICV) injection of 0.02 nmol of Hypothalamus CRF, CRF-injected chicks ate less than vehicle chicks while no effect on water intake was observed at 30 min Paraventricular nucleus post-injection. In subsequent experiments, the hypothalamus samples were processed at 60 min post-injection. The CRF-injected chicks had more c-Fos immunoreactive cells in the arcuate nucleus (ARC), dorsomedial nucleus (DMN), ventromedial hypothalamus (VMH), and paraventricular nucleus (PVN) of the hypothalamus than ve- hicle-treated chicks. CRF injection was associated with decreased whole hypothalamic mRNA abundance of neuropeptide Y receptor sub-type 1 (NPYR1). In the ARC, CRF-injected chicks expressed more CRF and CRF receptor sub-type 2 (CRFR2) mRNA but less agouti-related peptide (AgRP), NPY, and NPYR1 mRNA than ve- hicle-injected chicks. -
Searching for Novel Peptide Hormones in the Human Genome Olivier Mirabeau
Searching for novel peptide hormones in the human genome Olivier Mirabeau To cite this version: Olivier Mirabeau. Searching for novel peptide hormones in the human genome. Life Sciences [q-bio]. Université Montpellier II - Sciences et Techniques du Languedoc, 2008. English. tel-00340710 HAL Id: tel-00340710 https://tel.archives-ouvertes.fr/tel-00340710 Submitted on 21 Nov 2008 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE MONTPELLIER II SCIENCES ET TECHNIQUES DU LANGUEDOC THESE pour obtenir le grade de DOCTEUR DE L'UNIVERSITE MONTPELLIER II Discipline : Biologie Informatique Ecole Doctorale : Sciences chimiques et biologiques pour la santé Formation doctorale : Biologie-Santé Recherche de nouvelles hormones peptidiques codées par le génome humain par Olivier Mirabeau présentée et soutenue publiquement le 30 janvier 2008 JURY M. Hubert Vaudry Rapporteur M. Jean-Philippe Vert Rapporteur Mme Nadia Rosenthal Examinatrice M. Jean Martinez Président M. Olivier Gascuel Directeur M. Cornelius Gross Examinateur Résumé Résumé Cette thèse porte sur la découverte de gènes humains non caractérisés codant pour des précurseurs à hormones peptidiques. Les hormones peptidiques (PH) ont un rôle important dans la plupart des processus physiologiques du corps humain.