DOCSLIB.ORG

Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A University of Kentucky UKnowledge Spinal Cord and Brain Injury Research Center Spinal Cord and Brain Injury Research Faculty Publications 5-2016 Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A. Schaefer University of Iowa Marcus A. Toral University of Iowa Gabriel Velez University of Iowa Allison J. Cox University of Iowa Sheila A. Baker University of Iowa See next page for additional authors Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/scobirc_facpub Part of the Neurology Commons Repository Citation Schaefer, Kellie A.; Toral, Marcus A.; Velez, Gabriel; Cox, Allison J.; Baker, Sheila A.; Borcherding, Nicholas C.; Colgan, Diana F.; Bondada, Vimala; Mashburn, Charles B.; Yu, Chen Guang; Geddes, James W.; Tsang, Stephen H.; Bassuk, Alexander G.; and Mahajan, Vinit B., "Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses" (2016). Spinal Cord and Brain Injury Research Center Faculty Publications. 12. https://uknowledge.uky.edu/scobirc_facpub/12 This Article is brought to you for free and open access by the Spinal Cord and Brain Injury Research at UKnowledge. It has been accepted for inclusion in Spinal Cord and Brain Injury Research Center Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Authors Kellie A. Schaefer, Marcus A. Toral, Gabriel Velez, Allison J. Cox, Sheila A. Baker, Nicholas C. Borcherding, Diana F. Colgan, Vimala Bondada, Charles B. Mashburn, Chen Guang Yu, James W. Geddes, Stephen H. Tsang, Alexander G. Bassuk, and Vinit B. Mahajan Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Notes/Citation Information Published in Investigative Ophthalmology & Visual Science, v. 57, no. 6, p. 2509-2521. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Digital Object Identifier (DOI) https://doi.org/10.1167/iovs.15-18680 This article is available at UKnowledge: https://uknowledge.uky.edu/scobirc_facpub/12 Retinal Cell Biology Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A. Schaefer,1,2 Marcus A. Toral,1–3 Gabriel Velez,1–3 Allison J. Cox,4 Sheila A. Baker,2,5 Nicholas C. Borcherding,1,3 Diana F. Colgan,1,2 Vimala Bondada,6 Charles B. Mashburn,6 Chen-Guang Yu,6 James W. Geddes,6 Stephen H. Tsang,7,8 Alexander G. Bassuk,4,9 and Vinit B. Mahajan1,2 1Omics Laboratory, University of Iowa, Iowa City, Iowa, United States 2Department of Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States 3Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, United States 4Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States 5Department of Biochemistry, University of Iowa, Iowa City, Iowa, United States 6Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky, United States 7Barbara & Donald Jonas Stem Cell Laboratory, and Bernard & Shirlee Brown Glaucoma Laboratory, Department of Pathology & Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, United States 8Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, United States 9Neurology, University of Iowa, Iowa City, Iowa, United States Correspondence: Vinit B. Mahajan, PURPOSE. We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular Department of Ophthalmology and compartments. Visual Sciences, The University of Iowa,200HawkinsDrive,IowaCity, METHODS. CAPN5 gene variants were classified using the exome variant server, and RNA- IA 52242, USA; sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina [email protected]. and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and Submitted: November 19, 2015 mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines Accepted: February 28, 2016 and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions. Citation: Schaefer KA, Toral MA, Velez G, et al. Calpain-5 expression in the RESULTS. Most CAPN5 genetic variation occurs outside its protease core; and searches of retina localizes to photoreceptor syn- cancer and epilepsy/autism genetic databases found no variants similar to hyperactivating apses. Invest Ophthalmol Vis Sci. retinal disease alleles. The mouse retina expressed one transcript for CAPN5 plus those of 2016;57:2509–2521. DOI:10.1167/ nine other calpains, similar to the human retina. In Y79 retinoblastoma cells, the level of iovs.15-18680 CAPN5 transcript was very low. Immunohistochemistry detected CAPN5 expression in the inner and outer nuclear layers and at synapses in the outer plexiform layer. Western analysis of fractionated retinal extracts confirmed CAPN5 synapse localization. Western blots of fractionated brain neuronal extracts revealed distinct subcellular patterns and the potential presence of autoproteolytic CAPN5 domains. CONCLUSIONS. CAPN5 is moderately expressed in the retina and, despite higher expression in other tissues, hyperactive disease mutants of CAPN5 only manifest as eye disease. At the cellular level, CAPN5 is expressed in several different functional compartments. CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles. Keywords: CAPN5, calpain, autosomal dominant neovascular inflammatory vitreoretinopathy, ADNIV utation of the calcium-activated protease calpain-5 disease allele reduces the calcium level required for protease M (CAPN5) can cause a severe blinding disease, autosomal activity.7 Thus, the eye-restricted phenotype likely reflects the dominant neovascular inflammatory vitreoretinopathy (ADNIV, extraordinarily high calcium concentrations in the retina, OMIM #193235).1–5 In their twenties, ADNIV patients begin to where such a hyperactive calcium-dependent protease could display a synaptic signaling defect and intraocular inflammation be particularly damaging.3,5 (uveitis). Over the ensuing five decades, they experience retinal Increased calpain activity is a feature of many eye-related degeneration, retinal neovascularization, and intraocular fibro- pathologies, including retinal degeneration,8,9 retinal hypox- sis, culminating in phthisis and blindness.1–3 Although CAPN5 ia,10–13 retinitis pigmentosa,14–16 retinal detachment,17 and is expressed in many tissues, ADNIV patients only manifest glaucoma.18,19 Retinal damage from these pathologies can be disease in the eye.6 Autosomal dominant neovascular inflam- lessened by administering the calpain inhibitor SJA6017.8,20–22 matory vitreoretinopathy CAPN5 is hyperactive, since the However, since the human retina expresses several calpains, it iovs.arvojournals.org j ISSN: 1552-5783 2509 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/935270/ on 07/10/2017 Calpain-5 Expression in the Retina IOVS j May 2016 j Vol. 57 j No. 6 j 2510 is not known which isoform(s) SJA6017 inhibits. Both CAPN1 Collaboration (phs000298). Only those consented for autism and CAPN2 are expressed in the retina and show increased research only (AO) were downloaded. The data set(s) were activity in other neurodegenerative conditions and hypoxic deposited by the ARRA Autism Sequencing Collaborative, an cell death.8,20 CAPN10 and calpastatin also are expressed in ARRA funded research initiative. Support for the Autism the retina23,24 and CAPN3 expresses a retina-specific splice Sequencing Collaborative was provided by Grants R01- variant in rats.8,25 Although CAPN3 is linked to limb-girdle MH089208 awarded to Mark Daly, R01-MH089175 awarded muscular dystrophy type 2A,26 it is not associated with any to Richard Gibbs, R01-MH089025 awarded to Joseph Bux- known retinal disease. CAPN5, the most distant calpain family baum, R01-MH089004 awarded to Gerard Schellenberg, and ortholog,7 is the only retinal calpain known directly to trigger R01-MH089482 awarded to James Sutcliffe. retinal disease in humans. Inhibition of CAPN5 might be Exome vcf files from the Epi4k Epilepsy Phenome/Genome therapeutic, but a specific inhibitor has never been isolated; Project (EPGP) were requested and downloaded from dbGAP and sequence analysis shows CAPN5 does not bind calpastatin, (dbGAP Study Accession, phs000653.v2.p1). Our appreciation the endogenous calpain inhibitor.7,27 goes to the Epilepsy Epi4k consortium: Discovery in Epilepsy To increase our understanding of CAPN5 in the healthy study (NINDS U01-NS077303) and the Epilepsy Genome/ retina and during ADNIV, we characterized CAPN5 mRNA and Phenome Project (EPGP-NINDS U01-NS053998).31,32 protein expression in the normal retina. We also drew from rich compilations of genetic-variance expression databases and Cell Culture, Reagents, and Antibodies performed antibody epitope-structure analysis, immunohisto- chemistry, and subcellular fractionation. Cell lines HEK293T, SH-SY5Y, and Y79 were purchased from the American Type Culture Collection (ATCC; Manassas, VA, USA). Antibodies used were anti-GAPDH antibody (sc-32233), goat anti- METHODS rabbit, and goat anti-mouse secondary antibodies (Santa
Load more

Recommended publications
  • Universidade Estadual De Campinas Instituto De Biologia
    UNIVERSIDADE ESTADUAL DE CAMPINAS INSTITUTO DE BIOLOGIA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA CAMPINAS 2016 1 VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA Dissertação apresentada ao Instituto de Biologia da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do Título de Mestra em Biologia Funcional e Molecular na área de concentração de Bioquímica. Dissertation presented to the Institute of Biology of the University of Campinas in partial fulfillment of the requirements for the degree of Master in Functional and Molecular Biology, in the area of Biochemistry. ESTE ARQUIVO DIGITAL CORRESPONDE À VERSÃO FINAL DA DISSERTAÇÃO DEFENDIDA PELA ALUNA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA E ORIENTADA PELO DANIEL MARTINS-DE-SOUZA. Orientador: Daniel Martins-de-Souza CAMPINAS 2016 2 Agência(s) de fomento e nº(s) de processo(s): CNPq, 151787/2F2014-0 Ficha catalográfica Universidade Estadual de Campinas Biblioteca do Instituto de Biologia Mara Janaina de Oliveira - CRB 8/6972 Saia-Cereda, Verônica Aparecida Monteiro, 1988- Sa21p O proteoma do corpo caloso da esquizofrenia / Verônica Aparecida Monteiro Saia Cereda. – Campinas, SP : [s.n.], 2016. Orientador: Daniel Martins de Souza. Dissertação (mestrado) – Universidade Estadual de Campinas, Instituto de Biologia. 1. Esquizofrenia. 2. Espectrometria de massas. 3. Corpo caloso.
    [Show full text]
  • Calpain-5 Gene Expression in the Mouse Eye and Brain
    Schaefer et al. BMC Res Notes (2017) 10:602 DOI 10.1186/s13104-017-2927-8 BMC Research Notes RESEARCH NOTE Open Access Calpain‑5 gene expression in the mouse eye and brain Kellie Schaefer1, MaryAnn Mahajan1, Anuradha Gore1, Stephen H. Tsang3, Alexander G. Bassuk4 and Vinit B. Mahajan1,2* Abstract Objective: Our objective was to characterize CAPN5 gene expression in the mouse central nervous system. Mouse brain and eye sections were probed with two high-afnity RNA oligonucleotide analogs designed to bind CAPN5 RNA and one scramble, control oligonucleotide. Images were captured in brightfeld. Results: CAPN5 RNA probes were validated on mouse breast cancer tumor tissue. In the eye, CAPN5 was expressed in the ganglion cell, inner nuclear and outer nuclear layers of the retina. Signal could not be detected in the ciliary body or the iris because of the high density of melanin. In the brain, CAPN5 was expressed in the granule cell layers of the hippocampus and cerebellum. There was scattered expression in pons. The visual cortex showed faint signal. Most signal in the brain was in a punctate pattern. Keywords: CAPN5, Calpain, In situ hybridization, Retina, Brain, Gene expression Introduction pigmentosa, retinal neovascularization, and proliferative Calpain-5 (CAPN5) is a member of the calpain family of retinopathy. Which ultimately leads to blindness [20]. calcium-activated proteases that target a variety of path- Currently there is no treatment. ways to exert control over numerous processes, includ- An important question to understanding how CAPN5 ing tissue necrosis, cytoskeletal remodeling, cell-cycle leads to disease is identifying which tissues CAPN5 is control, cell migration, myofbril turnover, regulation expressed in and the levels of CAPN5 in those tissues.
    [Show full text]
  • Reconstructability Analysis As a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases
    Portland State University PDXScholar Systems Science Faculty Publications and Presentations Systems Science 3-2010 Reconstructability Analysis As A Tool For Identifying Gene-Gene Interactions In Studies Of Human Diseases Stephen Shervais Eastern Washington University Patricia L. Kramer Oregon Health & Science University Shawn K. Westaway Oregon Health & Science University Nancy J. Cox University of Chicago Martin Zwick Portland State University, [email protected] Follow this and additional works at: https://pdxscholar.library.pdx.edu/sysc_fac Part of the Bioinformatics Commons, Diseases Commons, and the Genomics Commons Let us know how access to this document benefits ou.y Citation Details Shervais, S., Kramer, P. L., Westaway, S. K., Cox, N. J., & Zwick, M. (2010). Reconstructability Analysis as a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases. Statistical Applications In Genetics & Molecular Biology, 9(1), 1-25. This Article is brought to you for free and open access. It has been accepted for inclusion in Systems Science Faculty Publications and Presentations by an authorized administrator of PDXScholar. Please contact us if we can make this document more accessible: [email protected]. Statistical Applications in Genetics and Molecular Biology Volume 9, Issue 1 2010 Article 18 Reconstructability Analysis as a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases Stephen Shervais∗ Patricia L. Kramery Shawn K. Westawayz Nancy J. Cox∗∗ Martin Zwickyy ∗Eastern Washington University, [email protected] yOregon Health & Science University, [email protected] zOregon Health & Science University, [email protected] ∗∗University of Chicago, [email protected] yyPortland State University, [email protected] Copyright c 2010 The Berkeley Electronic Press.
    [Show full text]
  • Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2010 Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis Ryan Fassnacht Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Physiology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2246 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Ryan C. Fassnacht 2010 All Rights Reserved Molecular Mechanisms Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. by Ryan Christopher Fassnacht, B.S. Hampden Sydney University, 2005 M.S. Virginia Commonwealth University, 2010 Director: Valeria Mas, Ph.D., Associate Professor of Surgery and Pathology Division of Transplant Department of Surgery Virginia Commonwealth University Richmond, Virginia July 9, 2010 Acknowledgement The Author wishes to thank his family and close friends for their support. He would also like to thank the members of the molecular transplant team for their help and advice. This project would not have been possible with out the help of Dr. Valeria Mas and her endearing
    [Show full text]
  • Propranolol-Mediated Attenuation of MMP-9 Excretion in Infants with Hemangiomas
    Supplementary Online Content Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.4773 eTable. List of All of the Proteins Identified by Proteomics This supplementary material has been provided by the authors to give readers additional information about their work. © 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable. List of All of the Proteins Identified by Proteomics Protein Name Prop 12 mo/4 Pred 12 mo/4 Δ Prop to Pred mo mo Myeloperoxidase OS=Homo sapiens GN=MPO 26.00 143.00 ‐117.00 Lactotransferrin OS=Homo sapiens GN=LTF 114.00 205.50 ‐91.50 Matrix metalloproteinase‐9 OS=Homo sapiens GN=MMP9 5.00 36.00 ‐31.00 Neutrophil elastase OS=Homo sapiens GN=ELANE 24.00 48.00 ‐24.00 Bleomycin hydrolase OS=Homo sapiens GN=BLMH 3.00 25.00 ‐22.00 CAP7_HUMAN Azurocidin OS=Homo sapiens GN=AZU1 PE=1 SV=3 4.00 26.00 ‐22.00 S10A8_HUMAN Protein S100‐A8 OS=Homo sapiens GN=S100A8 PE=1 14.67 30.50 ‐15.83 SV=1 IL1F9_HUMAN Interleukin‐1 family member 9 OS=Homo sapiens 1.00 15.00 ‐14.00 GN=IL1F9 PE=1 SV=1 MUC5B_HUMAN Mucin‐5B OS=Homo sapiens GN=MUC5B PE=1 SV=3 2.00 14.00 ‐12.00 MUC4_HUMAN Mucin‐4 OS=Homo sapiens GN=MUC4 PE=1 SV=3 1.00 12.00 ‐11.00 HRG_HUMAN Histidine‐rich glycoprotein OS=Homo sapiens GN=HRG 1.00 12.00 ‐11.00 PE=1 SV=1 TKT_HUMAN Transketolase OS=Homo sapiens GN=TKT PE=1 SV=3 17.00 28.00 ‐11.00 CATG_HUMAN Cathepsin G OS=Homo
    [Show full text]
  • To Study Mutant P53 Gain of Function, Various Tumor-Derived P53 Mutants
    Differential effects of mutant TAp63γ on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science By Shama K Khokhar M.Sc., Bilaspur University, 2004 B.Sc., Bhopal University, 2002 2007 1 COPYRIGHT SHAMA K KHOKHAR 2007 2 WRIGHT STATE UNIVERSITY SCHOOL OF GRADUATE STUDIES Date of Defense: 12-03-07 I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY SHAMA KHAN KHOKHAR ENTITLED Differential effects of mutant TAp63γ on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression BE ACCEPTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Master of Science Madhavi P. Kadakia, Ph.D. Thesis Director Daniel Organisciak , Ph.D. Department Chair Committee on Final Examination Madhavi P. Kadakia, Ph.D. Steven J. Berberich, Ph.D. Michael Leffak, Ph.D. Joseph F. Thomas, Jr., Ph.D. Dean, School of Graduate Studies 3 Abstract Khokhar, Shama K. M.S., Department of Biochemistry and Molecular Biology, Wright State University, 2007 Differential effect of TAp63γ mutants on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression. p63, a member of the p53 gene family, known to play a role in development, has more recently also been implicated in cancer progression. Mice lacking p63 exhibit severe developmental defects such as limb truncations, abnormal skin, and absence of hair follicles, teeth, and mammary glands. Germline missense mutations of p63 have been shown to be responsible for several human developmental syndromes including SHFM, EEC and ADULT syndromes and are associated with anomalies in the development of organs of epithelial origin.
    [Show full text]
  • Characterization of the Goose CAPN3 Gene and Its Expression Pattern in Muscle Tissues of Sichuan White Geese at Different Growth Stages
    http://www.jstage.jst.go.jp/browse/jpsa doi:10.2141/ jpsa.0170150 Copyright Ⓒ 2018, Japan Poultry Science Association. Characterization of the Goose CAPN3 Gene and its Expression Pattern in Muscle Tissues of Sichuan White Geese at Different Growth Stages Hengyong Xu*, Yahui Zhang*, Quan Zou, Liang Li, Chunchun Han, Hehe Liu, Jiwei Hu, Tao Zhong and Yan Wang Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China Calpain 3 (CAPN3), also known as p94, is associated with multiple production traits in domestic animals. However, the molecular characteristics of the CAPN3 gene and its expression profile in goose tissues have not been reported. In this study, CAPN3 cDNA of the Sichuan white goose was cloned, sequenced, and characterized. The CAPN3 full-length cDNA sequence consists of a 2,316-bp coding sequence (CDS) that encodes 771 amino acids with a molecular mass of 89,019 kDa. The protein was predicted to have no signal peptide, but several N-glycosylation, O- glycosylation, and phosphorylation sites. The secondary structure of CAPN3 was predicted to be 38.65% α-helical. Sequence alignment showed that CAPN3 of Sichuan white goose shared more than 90% amino acid sequence similarity with those of Japanese quail, turkey, helmeted guineafowl, duck, pigeon, and chicken. Phylogenetic tree analysis showed that goose CAPN3 has a close genetic relationship and small evolutionary distance with those of the birds. qRT-PCR analysis showed that in 15-day-old animals, the expression level of CAPN3 was significantly higher in breast muscle than in thigh tissues.
    [Show full text]
  • Evaluation of the Genetic Susceptibility to the Metabolic Syndrome by the CAPN10 SNP19 Gene in the Population of South Benin
    International Journal of Molecular Biology: Open Access Research Article Open Access Evaluation of the genetic susceptibility to the metabolic syndrome by the CAPN10 SNP19 gene in the population of South Benin Abstract Volume 4 Issue 6 - 2019 Metabolic syndrome is a multifactorial disorder whose etiology is resulting from the Nicodème Worou Chabi,1,2 Basile G interaction between genetic and environmental factors. Calpain 10 (CAPN10) is the first Sognigbé,1 Esther Duéguénon,1 Véronique BT gene associated with type 2 diabetes that has been identified by positional cloning with 1 1 sequencing method. This gene codes for cysteine ​​protease; ubiquitously expressed in all Tinéponanti, Arnaud N Kohonou, Victorien 2 1 tissues, it is involved in the fundamental physiopathological aspects of insulin resistance T Dougnon, Lamine Baba Moussa and insulin secretion of type 2 diabetes. The goal of this study was to evaluate the genetic 1Department of Biochemistry and Cell Biology, University of susceptibility to the metabolic syndrome by the CAPN10 gene in the population of southern Abomey-Calavi, Benin 2 Benin. This study involved apparently healthy individuals’ aged 18 to 80 in four ethnic Laboratory of Research in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Benin groups in southern Benin. It included 74 subjects with metabolic syndrome and 323 non- metabolic syndrome patients who served as controls, with 222 women versus 175 men Correspondence: Nicodème Worou Chabi, Laboratory with an average age of 40.58 ± 14.03 years old. All subjects were genotyped for the SNP of Biochemistry and Molecular Biology, Department of 19 polymorphism of the CAPN10 gene with the PCR method in order to find associations Biochemistry and Cell Biology, Faculty of Science and between this polymorphism and the metabolic syndrome.
    [Show full text]
  • Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes.
    [Show full text]
  • A Model for Profiling the Emolecular Effects of Alcohol
    The Pharmacogenomics Journal (2015) 15, 177–188 © 2015 Macmillan Publishers Limited All rights reserved 1470-269X/15 www.nature.com/tpj ORIGINAL ARTICLE The synaptoneurosome transcriptome: a model for profiling the emolecular effects of alcohol D Most1,2, L Ferguson1,2, Y Blednov1, RD Mayfield1 and RA Harris1 Chronic alcohol consumption changes gene expression, likely causing persistent remodeling of synaptic structures via altered translation of mRNAs within synaptic compartments of the cell. We profiled the transcriptome from synaptoneurosomes (SNs) and paired total homogenates (THs) from mouse amygdala following chronic voluntary alcohol consumption. In SN, both the number of alcohol-responsive mRNAs and the magnitude of fold-change were greater than in THs, including many GABA-related mRNAs upregulated in SNs. Furthermore, SN gene co-expression analysis revealed a highly connected network, demonstrating coordinated patterns of gene expression and highlighting alcohol-responsive biological pathways, such as long-term potentiation, long-term depression, glutamate signaling, RNA processing and upregulation of alcohol-responsive genes within neuroimmune modules. Alterations in these pathways have also been observed in the amygdala of human alcoholics. SNs offer an ideal model for detecting intricate networks of coordinated synaptic gene expression and may provide a unique system for investigating therapeutic targets for the treatment of alcoholism. The Pharmacogenomics Journal (2015) 15, 177–188; doi:10.1038/tpj.2014.43; published online 19 August 2014 INTRODUCTION mRNAs from SN15,16,18,19 and TH samples from mouse amygdala, a Alcohol dependence is a severe and widespread disease. Over 17 brain region known to be involved with the negative reinforce- 20 million Americans suffer from alcohol-related problems; total cost ment of alcohol and other drugs of abuse.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Calpain-10 Regulates Actin Dynamics by Proteolysis of Microtubule-Associated Protein 1B
    www.nature.com/scientificreports OPEN Calpain-10 regulates actin dynamics by proteolysis of microtubule-associated protein 1B Received: 15 September 2015 Tomohisa Hatta1, Shun-ichiro Iemura1,6, Tomokazu Ohishi2, Hiroshi Nakayama3, Accepted: 1 November 2018 Hiroyuki Seimiya 2, Takao Yasuda4, Katsumi Iizuka5, Mitsunori Fukuda4, Jun Takeda5, Published: xx xx xxxx Tohru Natsume1 & Yukio Horikawa5 Calpain-10 (CAPN10) is the calpain family protease identifed as the frst candidate susceptibility gene for type 2 diabetes mellitus (T2DM). However, the detailed molecular mechanism has not yet been elucidated. Here we report that CAPN10 processes microtubule associated protein 1 (MAP1) family proteins into heavy and light chains and regulates their binding activities to microtubules and actin flaments. Immunofuorescent analysis of Capn10−/− mouse embryonic fbroblasts shows that MAP1B, a member of the MAP1 family of proteins, is localized at actin flaments rather than at microtubules. Furthermore, fuorescence recovery after photo-bleaching analysis shows that calpain-10 regulates actin dynamics via MAP1B cleavage. Moreover, in pancreatic islets from CAPN10 knockout mice, insulin secretion was signifcantly increased both at the high and low glucose levels. These fndings indicate that defciency of calpain-10 expression may afect insulin secretion by abnormal actin reorganization, coordination and dynamics through MAP1 family processing. Calpains are a family of intracellular non-lysosomal calcium-activated neutral cysteine proteases known to cleave various substrate proteins and modulate their activities. Tere are 16 calpains, some of which are ubiquitously expressed and others displaying tissue-specifc distribution. Some calpains contain a penta-EF-hand domain (typical or classical calpains), and others do not (atypical calpains). Several calpain family members are impli- cated in the development of various diseases including Alzheimer’s disease, cataracts, ischemic stroke, traumatic brain injury, limb-girdle muscular dystrophy 2A and type 2 diabetes mellitus (T2DM)1.
    [Show full text]