DOCSLIB.ORG

Functional Receptor Formylpeptide Receptor-Like-1 As a Factor, Uses the G Protein-Coupled Humanin, a Newly Identified Neuroprote

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Functional Receptor Formylpeptide Receptor-Like-1 As a Factor, Uses the G Protein-Coupled Humanin, a Newly Identified Neuroprote Humanin, a Newly Identified Neuroprotective Factor, Uses the G Protein-Coupled Formylpeptide Receptor-Like-1 as a Functional Receptor This information is current as of September 23, 2021. Guoguang Ying, Pablo Iribarren, Ye Zhou, Wanghua Gong, Ning Zhang, Zu-Xi Yu, Yingying Le, Youhong Cui and Ji Ming Wang J Immunol 2004; 172:7078-7085; ; doi: 10.4049/jimmunol.172.11.7078 Downloaded from http://www.jimmunol.org/content/172/11/7078 References This article cites 39 articles, 20 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/172/11/7078.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 23, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Humanin, a Newly Identified Neuroprotective Factor, Uses the G Protein-Coupled Formylpeptide Receptor-Like-1 as a Functional Receptor1 Guoguang Ying,* Pablo Iribarren,* Ye Zhou,* Wanghua Gong,† Ning Zhang,* Zu-Xi Yu,‡ Yingying Le,* Youhong Cui,* and Ji Ming Wang2* Alzheimer’s disease (AD) is characterized by overproduction of ␤ amyloid peptides in the brain with progressive loss of neuronal ␤ ␤ cells. The 42-aa form of the amyloid peptide (A 42) is implied as a major causative factor, because it is toxic to neurons and ␤ elicits inflammatory responses in the brain by activating microglial cells. Despite the overproduction of A 42, AD brain tissue also ␤ generates protective factor(s) that may antagonize the neurodestructive effect of A 42. Humanin is a gene cloned from an ap- parently normal region of an AD brain and encodes a 24-aa peptide. Both secreted and synthetic Humanin peptides protect Downloaded from ␤ neuronal cells from damage by A 42, and the effect of Humanin may involve putative cellular receptor(s). To elucidate the molecular identity of such receptor(s), we examined the activity of synthetic Humanin on various cells and found that Humanin induced chemotaxis of mononuclear phagocytes by using a human G protein-coupled formylpeptide receptor-like-1 (FPRL1) and ␤ its murine counterpart FPR2. Coincidentally, FPRL1 and FPR2 are also functional receptors used by A 42 to chemoattract and ␤ activate phagocytic cells. Humanin reduced the aggregation and fibrillary formation by suppressing the effect of A 42 on mono- ␤ ␤ http://www.jimmunol.org/ nuclear phagocytes. In neuroblast cells, Humanin and A 42 both activated FPRL1; however, only A 42 caused apoptotic death of the cells, and its cytopathic effect was blocked by Humanin. We conclude that Humanin shares human FPRL1 and mouse FPR2 ␤ with A 42 and suggest that Humanin may exert its neuroprotective effects by competitively inhibiting the access of FPRL1 to ␤ A 42. The Journal of Immunology, 2004, 172: 7078–7085. ␤ ␤ 3 verproduced amyloid peptides, the 42 aa (A 42) in play a dual role in the formation of senile plagues, by dissolving particular, play a central role in mediating neurotoxicity preformed plaques when the cells are in an activated state (e.g., O and the formation of senile plaques in the brains of Alz- under the influence by TGF-␤) (8), or by promoting A␤ aggrega- ␤ ␤ heimer’s disease (AD) (1). Elevated level of A 42, both in soluble tion after prolonged exposure to A 42 (9). Thus, it is important to by guest on September 23, 2021 (2, 3) and fibrillary (4) forms, can be directly cytotoxic to neuronal identify the molecular basis that may determine the beneficial vs ␤ cells (5). A 42 also may activate mononuclear phagocytes in the detrimental role of mononulear phagocytes in affecting the patho- brain to elicit inflammatory responses (6). In vitro, A␤ peptides are genesis of AD. taken up by monocytes and microglia, and stimulate these cells to ␤ A 42 interacts with human mononuclear phagocytes and neu- release proinflammatory cytokines and neurotoxic mediators (6, ronal cells typically through a receptor-mediated signaling path- 7). Consequently, mononuclear phagocytes in the brain of AD may ␤ way. A number of putative surface receptors for A 42 and its an- alogues on myeloid as well as neuronal cells have been described in the literature (10-16). We recently found that a member of the *Laboratory of Molecular Immunoregulation and †Basic Research Program, SAIC- Frederick, Center for Cancer Research, National Cancer Institute, Frederick, MD G protein-coupled formylpeptide receptor (FPR) family, FPR- 21702; and ‡Pathology Section, National Heart, Lung, and Blood Institute, National like-1 (FPRL1), and its murine counterpart, FPR2, mediate che- Institutes of Health, Bethesda, MD 20892 motaxis and activation of monocytes and microglia induced by Received for publication January 20, 2004. Accepted for publication March 23, 2004. ␤ A 42 (17, 18). The prototype FPR was originally identified in hu- The costs of publication of this article were defrayed in part by the payment of page man myeloid cells as a high affinity receptor for the bacterial che- charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. motactic peptide formyl-methionyl-leucyl-phenylalanine (fMLF). 1 The content of this publication does not necessarily reflect the views or policies of fMLF at micromolar concentration range also activates FPRL1, the Department of Health and Human Services, nor does mention of trade names, which is therefore defined as a low affinity fMLF receptor. The commercial products, or organizations imply endorsement by the U.S. government. mouse analogues of human FPR and FPRL1 are termed FPR1 and The publisher or recipient acknowledges right of the U.S. government to retain a ␤ nonexclusive, royalty-free license in and to any copyright covering the article. This FPR2, respectively (19, 20). The chemotactic activity of A 42 was project has been funded in part with federal funds from the National Cancer Institute, specific on human FPRL1 and mouse FPR2 because A␤ at a National Institutes of Health, under Contract NO1-CO-12400. Animal care was pro- 42 vided in accordance with the procedures outlined in the Guide for the Care and Use wide concentration range did not induce migration of cell lines of Laboratory Animals (National Institutes of Health Publication 86-23, 1985). transfected to overexpress human FPR or mouse FPR1 (17, 18, 2 ␤ Address correspondence and reprint requests to Dr. Ji Ming Wang, Laboratory of Mo- 21). In addition to mediating the chemotactic activity of A 42, lecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Fred- FPRL1 also participates in the process of endocytosis and subse- erick, Building 560, Room 31-40, Frederick, MD 21702. E-mail address: ␤ [email protected] quent aggregation of A 42 in mononuclear phagocytes. Moreover, 3 Abbreviations used in this paper: A␤, amyloid ␤; AD, Alzheimer’s disease; ERK, activation of FPRL1 overexpressed in cells of the nonhemopoietic extracellular signal-regulated kinase; fMLF, formyl-methionyl-leucyl-phenylalanine; ␤ origin by A 42 results in apoptotic cell death (9). FPR, formylpeptide receptor; FPRL1, FPR-like-1; HN, Humanin; MAPK, mitogen- activated protein kinase; PI, propidium iodide; RT, room temperature; W pep, W Despite the progressive nature of neurodegeneration, the occip- peptide; p-ERK, phospho-ERK. ital lobe in AD brains is rarely affected by the disease. This led to Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 The Journal of Immunology 7079 the hypothesis that the occipital lobe may produce protective fac- precoated with 50 ␮g/ml collagen type I (Collaborative Biomedical Prod- tors against AD-associated pathologic insults. Recently, a cDNA ucts, Bedford, MA) to favor the attachment of the cells. After incubation at was isolated from the occipital region of an AD brain that encodes 37°C (90 min for monocytes and microglial cells; 5 h for 293 cells), the filters were removed and stained, and the cells migrated across the filters a 24-aa neuroprotective peptide Humanin (HN) (22). Immunore- were counted under light microscope after coding the samples. The results active HN peptide was detected in the occipital lobe of AD brain, were expressed as chemotaxis index, which represents the fold increase in consistent with the origin from which its cDNA was isolated (23). the number of cells migrated in response to chemoattractants over the spon- When transfected into neuronal cells, HN protected the cells from taneous cell migration (in response to control medium). cytotoxicity caused by coexpression of a variety of genes coding Calcium (Ca2ϩ) mobilization for mutated amyloid precursors associated with familial forms of ␮ ␤ Cells were incubated with 2.5 M fura 2-acetoxymethyl ester (Molecular AD and aberrant production of A 42 (22). Addition of synthetic Probes, Eugene, OR) in loading medium (RPMI 1640, 10% FCS, 2 mM HN into neuronal cell culture also rescued the cells from apoptotic glutamine) for 60 min at room temperature (RT) at a concentration of 1 ϫ ␤ 7 death induced by exposure to A 42. The fact that secreted or ex- 10 cells/ml, washed once, and resuspended in saline buffer (138 mM ogenously introduced HN possessed neuroprotective capabilities NaCl, 1 mM KCl, 1 mM CaCl2, 10 mM HEPES (pH 7.4), 5 mM glucose, ϫ 6 suggests that cell surface receptor(s) for HN might exist.
Load more

Recommended publications
  • The Role of Inflammatory Pathways in Neuroblastoma Tumorigenesis — Igor Snapkov a Dissertation for the Degree of Philosophiae Doctor – August 2016 Contents
    Faculty of Health Sciences Department of Medical Biology Molecular Inflammation Research Group The role of inflammatory pathways in neuroblastoma tumorigenesis — Igor Snapkov A dissertation for the degree of Philosophiae Doctor – August 2016 Contents 1. List of publications .................................................................................................................. 2 2. List of abbreviations ................................................................................................................ 3 3. Introduction ............................................................................................................................. 5 3.1 Cancer and inflammation .................................................................................................. 5 3.2.1 Pattern recognition receptors and danger signals ............................................................ 7 3.2.2 Formyl peptide receptor 1 (FPR1) ................................................................................. 9 3.3.1 Chemokines................................................................................................................. 12 3.3.2 Chemerin ..................................................................................................................... 13 3.4 Neuroblastoma ................................................................................................................ 14 3.5 Hepatic clearance of danger signals ................................................................................
    [Show full text]
  • Receptor-Like 1 and -Like 2 This Information Is Current As of October 2, 2021
    Urokinase Induces Basophil Chemotaxis through a Urokinase Receptor Epitope That Is an Endogenous Ligand for Formyl Peptide Receptor-Like 1 and -Like 2 This information is current as of October 2, 2021. Amato de Paulis, Nunzia Montuori, Nella Prevete, Isabella Fiorentino, Francesca Wanda Rossi, Valeria Visconte, Guido Rossi, Gianni Marone and Pia Ragno J Immunol 2004; 173:5739-5748; ; doi: 10.4049/jimmunol.173.9.5739 Downloaded from http://www.jimmunol.org/content/173/9/5739 References This article cites 65 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/173/9/5739.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 2, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Urokinase Induces Basophil Chemotaxis through a Urokinase Receptor Epitope That Is an Endogenous Ligand for Formyl Peptide Receptor-Like 1 and -Like 21 Amato de Paulis,* Nunzia Montuori,† Nella Prevete,* Isabella Fiorentino,* Francesca Wanda Rossi,* Valeria Visconte,‡ Guido Rossi,‡ Gianni Marone,2* and Pia Ragno† Basophils circulate in the blood and are able to migrate into tissues at sites of inflammation.
    [Show full text]
  • Insights Into Nuclear G-Protein-Coupled Receptors As Therapeutic Targets in Non-Communicable Diseases
    pharmaceuticals Review Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases Salomé Gonçalves-Monteiro 1,2, Rita Ribeiro-Oliveira 1,2, Maria Sofia Vieira-Rocha 1,2, Martin Vojtek 1,2 , Joana B. Sousa 1,2,* and Carmen Diniz 1,2,* 1 Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; [email protected] (S.G.-M.); [email protected] (R.R.-O.); [email protected] (M.S.V.-R.); [email protected] (M.V.) 2 LAQV/REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal * Correspondence: [email protected] (J.B.S.); [email protected] (C.D.) Abstract: G-protein-coupled receptors (GPCRs) comprise a large protein superfamily divided into six classes, rhodopsin-like (A), secretin receptor family (B), metabotropic glutamate (C), fungal mating pheromone receptors (D), cyclic AMP receptors (E) and frizzled (F). Until recently, GPCRs signaling was thought to emanate exclusively from the plasma membrane as a response to extracellular stimuli but several studies have challenged this view demonstrating that GPCRs can be present in intracellular localizations, including in the nuclei. A renewed interest in GPCR receptors’ superfamily emerged and intensive research occurred over recent decades, particularly regarding class A GPCRs, but some class B and C have also been explored. Nuclear GPCRs proved to be functional and capable of triggering identical and/or distinct signaling pathways associated with their counterparts on the cell surface bringing new insights into the relevance of nuclear GPCRs and highlighting the Citation: Gonçalves-Monteiro, S.; nucleus as an autonomous signaling organelle (triggered by GPCRs).
    [Show full text]
  • The Role of Sphingosine 1- Phosphate in Neutrophil Trans-Migration
    The role of sphingosine 1- phosphate in neutrophil trans-migration Eirini Giannoudaki Thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy Institute of Cellular Medicine Newcastle University September 2015 Abstract Sphingosine 1-phosphate (S1P), a bioactive lipid mediator and ligand of 5 G-protein coupled receptors, is involved in many cellular processes including cell survival and proliferation, lymphocyte migration, and endothelial barrier function. As neutrophils are major mediators of inflammation, neutrophil trans-endothelial migration could be the target of therapeutic approaches to many inflammatory conditions. The aim of this project was to assess whether S1P can protect against inflammation by affecting neutrophil trans-endothelial migration, either by acting on neutrophils directly or indirectly through the endothelial cells. The direct effects of S1P on isolated human neutrophils from healthy volunteers were assessed. It was shown that S1P signals in neutrophils mainly through the receptors S1PR1 and S1PR4 and it induces phosphorylation of ERK1/2. Moreover, S1P pre- treatment enhances IL-8 induced phosphorylation. However, in chemotaxis assays, S1P pre-treated neutrophils showed no altered migration towards IL-8 in comparison to untreated neutrophils. Additionally, in an in vitro flow-based adhesion assay, S1P pre- treatment did not have a significant effect on IL-8 induced neutrophil adhesion to VCAM-1 and ICAM-1. Next, the effects of S1P on endothelial cells were measured. When HMEC-1 endothelial cell line and HUVEC primary endothelial cells were treated with S1P or S1P receptor agonists CYM5442 and CYM5541, the production of the chemokine IL-8 was induced. On the other hand, this treatment inhibited neutrophil trans-endothelial migration through HMEC-1 and HUVEC endothelial cells.
    [Show full text]
  • Modulation of the Hippocampal Neurogenic Program by the Circadian Clock Machinery and the Small Gtpase, Rasd1/ Dexras1
    Modulation of the Hippocampal Neurogenic Program by the Circadian Clock Machinery and the small GTPase, Rasd1/ Dexras1 By Pascale Bouchard Cannon A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Cell and Systems Biology University of Toronto © Copyright by Pascale Bouchard Cannon (2018) Modulation of the Hippocampal Neurogenic Program by the Circadian Clock Machinery and the small GTPase, Rasd1/ Dexras1 Pascale Bouchard Cannon Doctor of Philosophy Department of Cell and Systems Biology University of Toronto 2018 Abstract The mammalian hippocampal subgranular zone (SGZ) is home to a limited pool of quiescent neural stem/ progenitor cells (QNPs). These cells respond to intrinsic and extrinsic physiological changes, embark on the neurogenesis program and give rise to glutamatergic granule neurons that populate the dentate gyrus (DG). In this thesis, I uncovered two mediators of the neurogenic program: the circadian clock and the small GTPase, Dexras1. The circadian clock machinery controls daily timings in cellular events via the transcription- translation feedback loop (TTFL), which includes Bmal1 and Period2. In this thesis, I demonstrate the presence of the molecular clock and of rhythmic cell proliferation in the SGZ. The absence of Period2 abolishes the gating of cell cycle entrance of QNPs, whereas the genetic ablation of Bmal1 results in constitutively high levels of neurogenesis and cognitive defects. Mathematical model simulations show that the circadian clock may be essential in mediating cell-cycle inhibitors that targets the cyclin D/Cdk4-6 complex, and in turn disruptions in this system result in the abolishment of gating mechanisms. This study uncovers the interrelationship between the cell cycle and the circadian clock and emphasizes the importance of proper rhythmicity for hippocampal function.
    [Show full text]
  • New Development in Studies of Formyl‐Peptide Receptors: Critical Roles In
    Review New development in studies of formyl-peptide receptors: critical roles in host defense † † ‡ † ‡ Liangzhu Li,*, Keqiang Chen, , Yi Xiang,§ Teizo Yoshimura, Shaobo Su, Jianwei Zhu,* { ‖ † { Xiu-wu Bian, , ,1 and Ji Ming Wang , ,1 *Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong † University, Shanghai, China; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, ‡ MD, USA; Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China; §Department of Pulmonary { Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Pathology and Southwest ‖ Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China RECEIVED AUGUST 11, 2015; REVISED NOVEMBER 29, 2015; ACCEPTED DECEMBER 1, 2015. DOI: 10.1189/jlb.2RI0815-354RR ABSTRACT number of variants and the spectrum of ligands they interact with. Formyl-peptide receptors are a family of 7 transmem- The number and the sequences of genes coding for FPR members brane domain, Gi-protein-coupled receptors that pos- vary considerably among mammalian species. The human FPR sess multiple functions in many pathophysiologic family has 3 members, FPR1, FPR2,andFPR3 (formerly FPR, processes because of their expression in a variety of cell FPRL1,andFPRL2, respectively) [5–8]. The mouse FPR (mFPR or types and their capacity to interact with a variety of Fpr) gene family consists of at least 8 members [9]. mFPR1, now structurally diverse, chemotactic ligands. Accumulating officially termed Fpr1, is considered the mouse ortholog of human evidence demonstrates that formyl-peptide receptors FPR1,whereasFpr2 is structurally and functionally most similar to are critical mediators of myeloid cell trafficking in the human FPR2 [10].
    [Show full text]
  • Structural Basis of Ligand Binding Modes at the Human Formyl Peptide Receptor 2
    ARTICLE https://doi.org/10.1038/s41467-020-15009-1 OPEN Structural basis of ligand binding modes at the human formyl peptide receptor 2 Tong Chen1,2,3,8, Muya Xiong 1,3,8, Xin Zong1,2,3, Yunjun Ge4, Hui Zhang1,2,3, Mu Wang1,5, Gye Won Han6, ✉ ✉ ✉ Cuiying Yi1, Limin Ma2, Richard D. Ye 7, Yechun Xu 1,3 , Qiang Zhao2,3 & Beili Wu 1,3,5 The human formyl peptide receptor 2 (FPR2) plays a crucial role in host defense and inflammation, and has been considered as a drug target for chronic inflammatory diseases. A 1234567890():,; variety of peptides with different structures and origins have been characterized as FPR2 ligands. However, the ligand-binding modes of FPR2 remain elusive, thereby limiting the development of potential drugs. Here we report the crystal structure of FPR2 bound to the potent peptide agonist WKYMVm at 2.8 Å resolution. The structure adopts an active con- formation and exhibits a deep ligand-binding pocket. Combined with mutagenesis, ligand binding and signaling studies, key interactions between the agonist and FPR2 that govern ligand recognition and receptor activation are identified. Furthermore, molecular docking and functional assays reveal key factors that may define binding affinity and agonist potency of formyl peptides. These findings deepen our understanding about ligand recognition and selectivity mechanisms of the formyl peptide receptor family. 1 CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Pudong, Shanghai, China. 2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Pudong, Shanghai, China.
    [Show full text]
  • The Role of FPR1 and GPR32 in Human Inflammation
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2015 The Role of FPR1 and GPR32 in Human Inflammation Schmid, Mattia Abstract: Inflammation is the natural reaction of the body toward tissue injury or pathogen invasion with the ultimate goal to restore homeostasis. When tissue resident APCs sense a perturbation, they release an array of chemokines and signalling molecules, which in turn attract further leukocytes into the affected tissue. Neutrophils, highly specialized microbial killers, are the first cells attracted fromthe blood stream to counter the noxious agents. In second place, the activated environment also promotes the development of classically activated M1 macrophages in the tissue, which work in concomitance with neutropihls and sustain the inflammatory reaction. Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-122768 Dissertation Published Version Originally published at: Schmid, Mattia. The Role of FPR1 and GPR32 in Human Inflammation. 2015, University of Zurich, Faculty of Medicine. The Role of FPR1 and GPR32 in Human Inflammation Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr. sc. nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät der Universität Zürich von Mattia Schmid von Flims, GR Promotionskomitee Prof. Dr. Thierry Hennet Prof. Dr. Martin Hersberger (Leitung der Dissertation) Prof. Dr. Arnold von Eckardstein Prof. Dr. Cornelia Halin Winter Zürich 2015 Summary Inflammation is the natural reaction of the body toward tissue injury or pathogen invasion with the ultimate goal to restore homeostasis. When tissue resident APCs sense a perturbation, they release an array of chemokines and signalling molecules, which in turn attract further leukocytes into the affected tissue.
    [Show full text]
  • The Molecular Gatekeeper Dexras1 Sculpts the Photic Responsiveness of the Mammalian Circadian Clock
    12984 • The Journal of Neuroscience, December 13 2006 • 26(50):12984–12995 Behavioral/Systems/Cognitive The Molecular Gatekeeper Dexras1 Sculpts the Photic Responsiveness of the Mammalian Circadian Clock Hai-Ying M. Cheng,1 Heather Dziema,1 Joseph Papp,1 Daniel P. Mathur,1 Margaret Koletar,2 Martin R. Ralph,2 Josef M. Penninger,3 and Karl Obrietan1 1Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, 2Centre for Biological Timing and Cognition and Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3, and 3Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria The mammalian master clock, located in the suprachiasmatic nucleus (SCN), is exquisitely sensitive to photic timing cues, but the key molecular events that sculpt both the phasing and magnitude of responsiveness are not understood. Here, we show that the Ras-like G-protein Dexras1 is a critical factor in these processes. Dexras1-deficient mice (dexras1Ϫ/Ϫ) exhibit a restructured nighttime phase response curve and a loss of gating to photic resetting during the day. Dexras1 affects the photic sensitivity by repressing or activating time-of-day-specific signaling pathways that regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK).Duringthelatenight,Dexras1limitsthecapacityofpituitaryadenylatecyclase(PAC)activatingpeptide(PACAP)/PAC1toaffect ERK/MAPK, and in the early night, light-induced phase delays, which are mediated predominantly by NMDA receptors, are reduced as reported previously. Daytime photic phase advances are mediated by a novel signaling pathway that does not affect the SCN core but rather stimulates ERK/MAPK in the SCN shell and triggers downregulation of clock protein expression.
    [Show full text]
  • UNIVERSITA' DI NAPOLI FEDERICO II New Insights in Formyl-Peptide
    UNIVERSITA’ DI NAPOLI FEDERICO II DOTTORATO DI RICERCA IN BIOCHIMICA E BIOLOGIA CELLULARE E MOLECOLARE XXVIII CICLO Melania Parisi New insights in Formyl-peptide Receptors functions Anno accademico 2014/2015 UNIVERSITA’ DI NAPOLI FEDERICO II DOTTORATO DI RICERCA BIOCHIMICA E BIOLOGIA CELLULARE E MOLECOLARE XXVIII CICLO New insights in Formyl-peptide Receptors functions Melania Parisi Relatore Coordinatore Prof. Rosario Ammendola Prof. Paolo Arcari Anno Accademico 2014/2015 Ringraziamenti e dediche Un altro percorso importante è giunto a termine. Un percorso ricco di sacrifici, passione e tante soddisfazioni. Un ringraziamento particolare va anzitutto al Prof. Rosario Ammendola, il primo ad aver creduto in me. Grazie per avermi guidato con saggi consigli e avermi trasmesso la sua esperienza professionale ed umana. La sua tenacia, accompagnata dalla sua ironia e dolcezza, mi ha sostenuta anche nei momenti più difficili. Ringrazio la Prof.ssa Giulia Russo per i preziosi suggerimenti per il miglioramento del presente lavoro. Un grazie speciale al Dott. Fabio Cattaneo che ha sempre creduto nelle mie capacità, grazie per avemi trasmesso la passione per la ricerca e di essere sempre stato presente. Vorrei esprime la mia gratitudine ai miei amici e colleghi di lavoro Dott.ssa Ilenia Agliarulo, Dott.ssa Maria Rosaria, Dott. Swann Danilo Matassa, Dott. Rosario Avolio e la Dott.ssa Diana Arzeni che non hanno mai smesso di supportami e sopportarmi e di non avermi mai lasciata sola. La vostra amicizia è stata un tesoro scoperto per caso in questa non facile avventura e senza la quale questo dottorato non sarebbe mai stato altrettanto prezioso. Non posso dimenticare l’immenso debito di gratitudine verso i miei genitori e mio fratello che hanno sostenuto le scelte personali e professionali più importanti della mia vita e non hanno mai mancato di incondizionato amore, ascolto e attenzione.
    [Show full text]
  • Blocking Formyl Peptide Receptor 1 This Information Is Current As of September 25, 2021
    Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide−Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1 This information is current as of September 25, 2021. Shun-Chin Yang, Pei-Jen Chung, Chiu-Ming Ho, Chan-Yen Kuo, Min-Fa Hung, Yin-Ting Huang, Wen-Yi Chang, Ya-Wen Chang, Kwok-Hon Chan and Tsong-Long Hwang J Immunol published online 13 May 2013 http://www.jimmunol.org/content/early/2013/05/12/jimmun Downloaded from ol.1202215 Supplementary http://www.jimmunol.org/content/suppl/2013/05/13/jimmunol.120221 http://www.jimmunol.org/ Material 5.DC1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 25, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published May 13, 2013, doi:10.4049/jimmunol.1202215 The Journal of Immunology Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide–Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1 Shun-Chin Yang,*,† Pei-Jen Chung,‡ Chiu-Ming Ho,*,x Chan-Yen Kuo,‡ Min-Fa Hung,‡ Yin-Ting Huang,‡ Wen-Yi Chang,‡ Ya-Wen Chang,‡ Kwok-Hon Chan,*,x and Tsong-Long Hwang‡,{ Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome.
    [Show full text]
  • International Union of Basic and Clinical Pharmacology. LXXX. the Class Frizzled Receptors□S
    Supplemental Material can be found at: /content/suppl/2010/11/30/62.4.632.DC1.html 0031-6997/10/6204-632–667$20.00 PHARMACOLOGICAL REVIEWS Vol. 62, No. 4 Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics 2931/3636111 Pharmacol Rev 62:632–667, 2010 Printed in U.S.A. International Union of Basic and Clinical Pharmacology. LXXX. The Class Frizzled Receptors□S Gunnar Schulte Section of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Abstract............................................................................... 633 I. Introduction: the class Frizzled and recommended nomenclature............................ 633 II. Brief history of discovery and some phylogenetics ......................................... 634 III. Class Frizzled receptors ................................................................ 634 A. Frizzled and Smoothened structure ................................................... 635 1. The cysteine-rich domain ........................................................... 635 2. Transmembrane and intracellular domains........................................... 636 3. Motifs for post-translational modifications ........................................... 636 B. Class Frizzled receptors as PDZ ligands............................................... 637 C. Lipoglycoproteins as receptor ligands ................................................. 638 Downloaded from IV. Coreceptors...........................................................................
    [Show full text]