Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies

Total Page:16

File Type:pdf, Size:1020Kb

Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies Hindawi Oxidative Medicine and Cellular Longevity Volume 2019, Article ID 7318796, 15 pages https://doi.org/10.1155/2019/7318796 Review Article Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies Vittoria Cenni ,1,2 Snezana Kojic,3 Cristina Capanni,1,2 Georgine Faulkner,4 and Giovanna Lattanzi 1,2 1CNR National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40126 Bologna, Italy 2IRCCS Istituto Ortopedico Rizzoli, 40126 Bologna, Italy 3Institute of Molecular Genetics and Genetic Engineering University of Belgrade, 11010 Belgrade, Serbia 4Department of Biology, University of Padua, 35121 Padua, Italy Correspondence should be addressed to Vittoria Cenni; [email protected] and Giovanna Lattanzi; [email protected] Received 4 March 2019; Revised 2 May 2019; Accepted 19 May 2019; Published 24 July 2019 Guest Editor: Andrey J. Serra Copyright © 2019 Vittoria Cenni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ankrd2 (ankyrin repeats containing domain 2) or Arpp (ankyrin repeat, PEST sequence, and proline-rich region) is a member of the muscle ankyrin repeat protein family. Ankrd2 is mostly expressed in skeletal muscle, where it plays an intriguing role in the transcriptional response to stress induced by mechanical stimulation as well as by cellular reactive oxygen species. Our studies in myoblasts from Emery-Dreifuss muscular dystrophy 2, a LMNA-linked disease affecting skeletal and cardiac muscles, demonstrated that Ankrd2 is a lamin A-binding protein and that mutated lamins found in Emery-Dreifuss muscular dystrophy change the dynamics of Ankrd2 nuclear import, thus affecting oxidative stress response. In this review, besides describing the latest advances related to Ankrd2 studies, including novel discoveries on Ankrd2 isoform-specific functions, we report the main findings on the relationship of Ankrd2 with A-type lamins and discuss known and potential mechanisms involving defective Ankrd2-lamin A interplay in the pathogenesis of muscular laminopathies. 1. Introduction anomalous expression level of Ankrd2, as well as defective nuclear recruitment of the protein, might contribute to a Ankrd2 (ankyrin repeats containing domain 2) or Arpp muscular phenotype. Very recently, we found that Ankrd2 (ankyrin repeat, PEST sequence, and proline-rich region) is is a novel interactor of A-type lamins, which are produced a member of the MARP (muscle ankyrin repeat protein) by the LMNA gene and are the major constituents of the family of proteins that also includes Ankrd1, or Carp nuclear lamina. Mutations of LMNA gene are the cause of a (Cardiac Ankyrin Repeat Protein), and Ankrd23, or DARP substantial number of pathologies, some of which affecting (Diabetes-related Ankyrin Repeat Protein) [1]. As we will skeletal and cardiac muscles. Moreover, altered expression describe in detail in this review, Ankrd2 is principally of Ankrd2 was detected in myopathies [2], cardiomyopathies expressed in skeletal muscle, where it plays an intriguing role [3], and some tumors [4]. In this review, apart from describ- in the transcriptional response to stress induced by mechan- ing the latest advances related to Ankrd2, including an ever- ical stimulation, as well as by cellular ROS (reactive oxygen growing interest for Ankrd2 isoform-specific functions, we species). In particular, although the Ankrd2 knockout mouse will report the main findings on Ankrd2 and its relation to model has revealed that Ankrd2 is not necessary for life nor lamins and discuss known and potential mechanisms, the direct cause of any muscular disorder, multiple evidence through which defective Ankrd2-lamin A interplay might obtained from muscular cell lines or primary cultures from have a role in the pathogenesis of LMNA-related muscular patients affected by muscular diseases suggest that an disorders. 2 Oxidative Medicine and Cellular Longevity 2. Ankrd2 in Striated Muscles of slow muscle fibers [17]), corroborating Ankrd2 prefer- ential expression in slow fibers [6]. Ankrd2, together with other proteins of the MARP family, is Although the existence of Ankrd2 isoforms was reported considered as STRaND (shuttling transcriptional regulators in 2003 by Miller et al. [7], their specific expression and local- and non-DNA-binding protein), having signature features: ization in human skeletal and cardiac muscles, as well as in shuttling from the cytoplasm to the nucleus, absence of primary human myoblasts and myotubes, have been recently DNA binding, and regulation of transcription via interaction determined by studies in which their discrimination was with transcription factors [5]. Recently, data from Wette enabled by specific antibodies [6, 18]. fi et al., obtained on single muscle bers, have shown that The most important Ankrd2 isoforms, namely, S-Ankrd2 > Ankrd2 is mostly found ( 70% of total Ankrd2) in the (333 aa) and M-Ankrd2 (360 aa), are identical, except for cytosol [6]. The remaining amount is distributed between 27 aa extension at the N-terminus of M-Ankrd2. Accord- intracellular structures, including the sarcomere and the ing to qPCR results, the expression of Ankrd2 isoforms is fl nucleus, with proportions that re ect the physiology, such regulated at the transcriptional level [18]. S-Ankrd2 is as the type (slow/fast) or the condition (forming/mature/ expressed in both heart and skeletal muscles [18] where fi regenerating/injured), of the ber considered. In healthy it is the predominant form [6, 18]. The well-known chess- striated muscle, Ankrd2 is found at the sarcomeric I-band board pattern of Ankrd2 expression observed in transver- [7, 8] where it contributes to the formation and function of sal sections of skeletal muscle may be attributed almost the I-band mechanosensory complex, probably via interac- exclusively to S-Ankrd2 [6, 18], which has been therefore tion with calpain 3 and the elastic portion of titin (N2A proposed as the canonical Ankrd2 isoform. Although still region) [7, 9]. As extensively described in the next sections, a matter of debate, in mature muscle fibers, the small Ankrd2 also interacts with nuclear proteins with both struc- amount of M-Ankrd2 has been identified in nuclei [18]. tural and enzymatic roles [1] and is accumulated in nuclei of In human myoblasts, S-Ankrd2 is expressed mainly in injured muscle [10]. An overview of the main structural and nuclei at a low level, while in myotubes, it is upregulated functional features of Ankrd2, including protein domains, and localized in the cytoplasm. M-Ankrd2 is also upregu- fi fi posttranslational modi cations, expression pro le, proposed lated upon differentiation of myoblasts to myotubes; ff functions, interacting proteins, and pathways a ected by however, it maintains its nuclear localization. Striking dif- ANKRD2 silencing in human myoblasts, is given in Table 1. ferences in expression and localization of Ankrd2 isoforms In the nucleus, Ankrd2 participates in the regulation of genes may mirror their different functions which however need fl involved in the cell cycle, myogenesis, and in ammatory to be further explored [18]. For example, M-Ankrd2 might – response [11 15]. Of note, in mature muscle cells, the have a more regulatory role, being predominantly nuclear, evidence reporting that the majority of Ankrd2 is freely while sarcomeric and cytosolic S-Ankrd2 may have a ff fi di usible in the cytosol [6] has for the rst time pointed to structural and downstream signaling role, respectively. the open question if Ankrd2, besides being involved in Domain organization, alignment, and updated database sarcomeric activity, might also participate in cellular func- entries for all five Ankrd2 isoforms are shown in tions in other subcellular districts, thus suggesting a role as Figures 1(a)–1(c), respectively. a downstream signal transducer in mechanosignaling path- ways. It is important to note that despite accumulated 2.2. Ankrd2 Expression in Cardiac Muscle. Ankrd2 is fi ndings from cell culture experiments, direct evidence of expressed in the human heart, including ventricles, the inter- Ankrd2 function in mature healthy and diseased striated ventricular septum, and the apex of the heart [4, 19], at a muscles is still missing. lower level compared to skeletal muscle. Ankrd2 expression in the heart is potentially regulated by cardiac-specific tran- 2.1. Ankrd2 Expression in Skeletal Muscle. Ankrd2 was scription factors Nkx2.5, Hand2, and Ankrd1 as demon- reported for the first time in a study performed in 2000 by strated by their interaction with the ANKRD2 promoter or Kemp and colleagues as a protein upregulated in murine by dual luciferase assay [20, 21]. Transcriptome profiling muscle exposed to prolonged passive stretch (7 days) [16]. confirmed a lower level of Ankrd2 in the ventricles of Preferential expression in skeletal muscle, more specifically human adult heart, compared to Ankrd1 [22]. Both S- and in slow (type I) muscle fibers, and responsiveness to mechan- M-Ankrd2 isoforms are expressed in cardiac muscle; they ical stress are signature features of this protein. Recently, have sarcomeric localization and are almost absent from Ankrd2 was confirmed to be the most abundant MARP nuclei [18]. The latter finding and the known interaction protein in human skeletal muscle, being ~30-fold more between Ankrd2 and the gap junction protein ZO-1 [20], expressed than DARP and ~150-fold more than Ankrd1 enriched in ICDs, suggest a role for Ankrd2 in intercellular [6]. In this study, performed on a group of four subjects, communication, which merits further investigation. In the absolute amount of Ankrd2 was subject-specific, ranging neonatal rat cardiomyocytes (NRCM), both sarcomeric and from 1.6 to 4.3 μmol/kg net weight, and proportional to the nuclear localizations of Ankrd2 were investigated during content of myosin heavy chain I (MHCI) protein, which is cellular differentiation and not shown to be affected by the a marker of slow (type I) muscle fibers [6].
Recommended publications
  • The Role of Z-Disc Proteins in Myopathy and Cardiomyopathy
    International Journal of Molecular Sciences Review The Role of Z-disc Proteins in Myopathy and Cardiomyopathy Kirsty Wadmore 1,†, Amar J. Azad 1,† and Katja Gehmlich 1,2,* 1 Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK; [email protected] (K.W.); [email protected] (A.J.A.) 2 Division of Cardiovascular Medicine, Radcliffe Department of Medicine and British Heart Foundation Centre of Research Excellence Oxford, University of Oxford, Oxford OX3 9DU, UK * Correspondence: [email protected]; Tel.: +44-121-414-8259 † These authors contributed equally. Abstract: The Z-disc acts as a protein-rich structure to tether thin filament in the contractile units, the sarcomeres, of striated muscle cells. Proteins found in the Z-disc are integral for maintaining the architecture of the sarcomere. They also enable it to function as a (bio-mechanical) signalling hub. Numerous proteins interact in the Z-disc to facilitate force transduction and intracellular signalling in both cardiac and skeletal muscle. This review will focus on six key Z-disc proteins: α-actinin 2, filamin C, myopalladin, myotilin, telethonin and Z-disc alternatively spliced PDZ-motif (ZASP), which have all been linked to myopathies and cardiomyopathies. We will summarise pathogenic variants identified in the six genes coding for these proteins and look at their involvement in myopathy and cardiomyopathy. Listing the Minor Allele Frequency (MAF) of these variants in the Genome Aggregation Database (GnomAD) version 3.1 will help to critically re-evaluate pathogenicity based on variant frequency in normal population cohorts.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Identification of Potential Markers for Type 2 Diabetes Mellitus Via Bioinformatics Analysis
    1868 MOLECULAR MEDICINE REPORTS 22: 1868-1882, 2020 Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis YANA LU1, YIHANG LI1, GUANG LI1* and HAITAO LU2* 1Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Jinghong, Yunnan 666100; 2Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China Received March 20, 2019; Accepted January 20, 2020 DOI: 10.3892/mmr.2020.11281 Abstract. Type 2 diabetes mellitus (T2DM) is a multifactorial and cell proliferation’. These candidate genes were also involved in multigenetic disease, and its pathogenesis is complex and largely different signaling pathways associated with ‘PI3K/Akt signaling unknown. In the present study, microarray data (GSE201966) of pathway’, ‘Rap1 signaling pathway’, ‘Ras signaling pathway’ β-cell enriched tissue obtained by laser capture microdissection and ‘MAPK signaling pathway’, which are highly associated were downloaded, including 10 control and 10 type 2 diabetic with the development of T2DM. Furthermore, a microRNA subjects. A comprehensive bioinformatics analysis of microarray (miR)-target gene regulatory network and a transcription data in the context of protein-protein interaction (PPI) networks factor-target gene regulatory network were constructed based was employed, combined with subcellular location information on miRNet and NetworkAnalyst databases, respectively. to mine the potential candidate genes for T2DM and provide Notably, hsa-miR‑192-5p, hsa-miR‑124-5p and hsa-miR‑335-5p further insight on the possible mechanisms involved. First, appeared to be involved in T2DM by potentially regulating the differential analysis screened 108 differentially expressed expression of various candidate genes, including procollagen genes.
    [Show full text]
  • Spatiotemporal Single-Cell Analysis Reveals Critical Roles of Mechano-Sensing Genes at the Border Zone in Remodeling After Myocardial Infarction
    Spatiotemporal single-cell analysis reveals critical roles of mechano-sensing genes at the border zone in remodeling after myocardial infarction Shintaro Yamada Tokyo University https://orcid.org/0000-0002-3240-358X Toshiyuki Ko The University of Tokyo Satoshi Hatsuse The University of Tokyo Seitaro Nomura The University of Tokyo Bo Zhang The University of Tokyo Zhehao Dai The University of Tokyo https://orcid.org/0000-0002-0363-7563 Shunsuke Inoue The University of Tokyo Masayuki Kubota The University of Tokyo Kosuke Sawami The University of Tokyo Takanobu Yamada The University of Tokyo Tatsuro Sassa The University of Tokyo Mikako Katagiri The University of Tokyo Kanna Fujita The University of Tokyo Manami Katoh The University of Tokyo Masamichi Ito The University of Tokyo Mutsuo Harada Page 1/21 The University of Tokyo Haruhiro Toko The University of Tokyo Norifumi Takeda The University of Tokyo https://orcid.org/0000-0003-4818-3347 Hiroyuki Morita The University of Tokyo Hiroyuki Aburatani The University of Tokyo Issei Komuro ( [email protected] ) The University of Tokyo Graduate School of Medicine Article Keywords: spatiotemporal single-cell analysis, myocardial infarction, left ventricular remodeling. Posted Date: June 22nd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-620498/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/21 Abstract The left ventricular remodeling after myocardial infarction (MI) causes heart failure, but its underlying mechanisms remain largely unknown. Here, we performed an integrative analysis of spatial transcriptomics and single cell RNA-seq in murine MI model and found that mechanical stress-response genes are expressed at the border zone and play a critical role in left ventricular remodeling after MI.
    [Show full text]
  • Identification of a Variant Hotspot in MYBPC3 and of a Novel CSRP3
    ORIGINAL ARTICLE Identification of a variant hotspot inMYBPC3 and of a novel CSRP3 autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy Martina Lipari1, Ewa Wypasek2,3, Marek Karpiński2, Lidia Tomkiewicz ‑Pająk2,4, Luigi Laino1, Francesco Binni1, Diana Giannarelli5, Paweł Rubiś2,4, Paweł Petkow ‑Dimitrow6,7, Anetta Undas2,7, Paola Grammatico1, Irene Bottillo1 1 Division of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo ‑Forlanini Hospital, Rome, Italy 2 John Paul II Hospital, Kraków, Poland 3 Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Kraków, Poland 4 Department of Cardiac Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland 5 Biostatistical Unit, Regina Elena National Cancer Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy 6 2nd Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland 7 Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland KEY WORDS ABSTRACT CSRP3 human KO, INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant hypertrophic alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, cardiomyopathy, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound MYBPC3 founder heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants mutation, Polish are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder population pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES This study aimed to assess the genetic background of HCM in a cohort of Polish patients.
    [Show full text]
  • Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes In
    ORIGINAL ARTICLE Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort Steven C. Elbein,1,2 Swapan K. Das,1,2 D. Michael Hallman,3 Craig L. Hanis,3 and Sandra J. Hasstedt4 OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes ype 2 diabetes is marked by a clear genetic diagnosis, and BMI. propensity, a high concordance in identical twins, tendencies for both diabetes and age of RESEARCH DESIGN AND METHODS—After removing outli- onset to be familial (1), and marked differences ers and problematic samples, we conducted linkage analysis T in prevalence among ethnic groups (2). Despite consider- using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 able evidence for a genetic predisposition, unraveling the diabetes, age of type 2 diabetes diagnosis, and BMI and nonpara- genetic etiology has been daunting, with few confirmed metric linkage analyses. Ordered subset analyses were con- genes identified from genome-wide linkage scans. Recent ducted ranking on age of type 2 diabetes diagnosis, BMI, waist successes with genome-wide association scans (3) have circumference, waist-to-hip ratio, and amount of European ad- greatly increased the number of confirmed genetic loci, mixture. Admixture mapping was conducted using 4,486 markers but these successes have been limited primarily to Cauca- not in linkage disequilibrium.
    [Show full text]
  • The Adaptation and Changes of Titin System Following Exercise Training Hassan Farhadi 1 and Mir Hojjat Mosavineghad 2
    Available online a t www.pelagiaresearchlibrary.com Pelagia Research Library European Journal of Experimental Biology, 2012, 2 (4):1256-1260 ISSN: 2248 –9215 CODEN (USA): EJEBAU The adaptation and changes of titin system following exercise training Hassan Farhadi 1 and Mir Hojjat Mosavineghad 2 1Department of Physical Education and Sport Sciences, Ahar branch, Islamic Azad University, Ahar, Iran 2Department of Physical Education and Sport Sciences, khoy branch, Islamic Azad University, khoy, Iran _____________________________________________________________________________________________ ABSTRACT Titin is a large structural protein in muscle that has the ability to store elastic energy. The specific structure of titin and its elastic nature has recently become better understood. In addition, the utilization of stored elastic energy in human movement and the significant contribution of not only tendon but muscle tissue itself to this process has been re-evaluated. In this study, we reviewed the effects of exercise training on titin system (titin expression and titin- complex proteins). Keywords: Titin, titin-complex proteins, exercise training _________________________________________________________________________________________ The giant sarcomeric protein titin is 3-4 MDa and spans the sarcomere from Z-line to M-line. Titin was first discovered in 1979 by Wang et. al. (1), who initially thought that titin was a collection of polypeptides that formed one large protein. Although titin’s physical identification eluded researchers for many years, probably due to its susceptibility to proteolytic cleavage, many scientists, including Earnest Starling and A.F. Huxley, posited its existence (2). Starling and Huxley modeled their theories on the premise that something within striated muscle was regulating passive properties. This is now known to be the role of titin, which is one peptide, encoded by a single gene, TTN (2).
    [Show full text]
  • CSRP3 Antibody Order 021-34695924 [email protected] Support 400-6123-828 50Ul [email protected] 100 Ul √ √ Web
    TD12922 CSRP3 Antibody Order 021-34695924 [email protected] Support 400-6123-828 50ul [email protected] 100 uL √ √ Web www.ab-mart.com.cn Description: Positive regulator of myogenesis. Acts as cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization. Proposed to contribute to the maintenance of muscle cell integerity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association. In vitro can inhibit PKC/PRKCA activity. Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity).May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation.
    [Show full text]
  • A Population-Specific Major Allele Reference Genome from the United
    Edith Cowan University Research Online ECU Publications Post 2013 2021 A population-specific major allele efr erence genome from the United Arab Emirates population Gihan Daw Elbait Andreas Henschel Guan K. Tay Edith Cowan University Habiba S. Al Safar Follow this and additional works at: https://ro.ecu.edu.au/ecuworkspost2013 Part of the Life Sciences Commons, and the Medicine and Health Sciences Commons 10.3389/fgene.2021.660428 Elbait, G. D., Henschel, A., Tay, G. K., & Al Safar, H. S. (2021). A population-specific major allele reference genome from the United Arab Emirates population. Frontiers in Genetics, 12, article 660428. https://doi.org/10.3389/ fgene.2021.660428 This Journal Article is posted at Research Online. https://ro.ecu.edu.au/ecuworkspost2013/10373 fgene-12-660428 April 19, 2021 Time: 16:18 # 1 ORIGINAL RESEARCH published: 23 April 2021 doi: 10.3389/fgene.2021.660428 A Population-Specific Major Allele Reference Genome From The United Arab Emirates Population Gihan Daw Elbait1†, Andreas Henschel1,2†, Guan K. Tay1,3,4,5 and Habiba S. Al Safar1,3,6* 1 Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates, 2 Department of Electrical Engineering and Computer Science, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates, 3 Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates, 4 Division of Psychiatry, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, WA, Australia, 5 School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia, 6 Department of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates The ethnic composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias.
    [Show full text]
  • Effects of Delayed NSAID Administration After Experimental Eccentric Contraction Injury – a Cellular and Proteomics Study Laura Bond Boise State University
    Boise State University ScholarWorks Biology Faculty Publications and Presentations Department of Biological Sciences 2-28-2017 Effects of Delayed NSAID Administration After Experimental Eccentric Contraction Injury – A Cellular and Proteomics Study Laura Bond Boise State University This document was originally published by Public Library of Science (PLOS) in PLOS ONE. This work is provided under a Creative Commons Public Domain 1.0 license. Details regarding the use of this work can be found at: http://creativecommons.org/publicdomain/zero/1.0/. doi: http://dx.doi.org/10.1371/journal.pone.0172486 RESEARCH ARTICLE Effects of delayed NSAID administration after experimental eccentric contraction injury ± A cellular and proteomics study Amy E. Bryant1,2*, Michael J. Aldape1,3, Clifford R. Bayer1, Eva J. Katahira1, Laura Bond4, Carrie D. Nicora5, Thomas L. Fillmore5, Therese R. W. Clauss5, Thomas O. Metz5, Bobbie- Jo Webb-Robertson5, Dennis L. Stevens1,2 1 U.S. Department of Veterans Affairs, Office of Research and Development, Boise, ID, United States of America, 2 University of Washington School of Medicine, Seattle, WA, United States of America, a1111111111 3 Northwest Nazarene University, Nampa, ID, United States of America, 4 Boise State University, Boise, ID, a1111111111 United States of America, 5 Pacific Northwest National Laboratory, Richland, WA, United States of America a1111111111 a1111111111 * [email protected], [email protected] a1111111111 Abstract OPEN ACCESS Background Citation: Bryant AE, Aldape MJ, Bayer CR, Katahira EJ, Bond L, Nicora CD, et al. (2017) Effects of Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs delayed NSAID administration after experimental (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain eccentric contraction injury ± A cellular and that peak 1±2 days post-injury.
    [Show full text]
  • Changes in Gene Methylation Patterns in Neonatal Murine Hearts
    Górnikiewicz et al. BMC Genomics (2016) 17:231 DOI 10.1186/s12864-016-2545-1 RESEARCH ARTICLE Open Access Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential Bartosz Górnikiewicz1, Anna Ronowicz2, Michał Krzemiński3 and Paweł Sachadyn1* Abstract Background: The neonatal murine heart is able to regenerate after severe injury; this capacity however, quickly diminishes and it is lost within the first week of life. DNA methylation is an epigenetic mechanism which plays a crucial role in development and gene expression regulation. Under investigation here are the changes in DNA methylation and gene expression patterns which accompany the loss of regenerative potential. Results: The MeDIP-chip (methylated DNA immunoprecipitation microarray) approach was used in order to compare global DNA methylation profiles in whole murine hearts at day 1, 7, 14 and 56 complemented with microarray transcriptome profiling. We found that the methylome transition from day 1 to day 7 is characterized by the excess of genomic regions which gain over those that lose DNA methylation. A number of these changes were retained until adulthood. The promoter genomic regions exhibiting increased DNA methylation at day 7 as compared to day 1 are significantly enriched in the genes critical for heart maturation and muscle development. Also, the promoter genomic regions showing an increase in DNA methylation at day 7 relative to day 1 are significantly enriched with a number of transcription factors binding motifs including those of Mfsd6l, Mef2c, Meis3, Tead4, and Runx1. Conclusions: The results indicate that the extensive alterations in DNA methylation patterns along the development of neonatal murine hearts are likely to contribute to the decline of regenerative capabilities observed shortly after birth.
    [Show full text]
  • Investigating the Effect of Chronic Activation of AMP-Activated Protein
    Investigating the effect of chronic activation of AMP-activated protein kinase in vivo Alice Pollard CASE Studentship Award A thesis submitted to Imperial College London for the degree of Doctor of Philosophy September 2017 Cellular Stress Group Medical Research Council London Institute of Medical Sciences Imperial College London 1 Declaration I declare that the work presented in this thesis is my own, and that where information has been derived from the published or unpublished work of others it has been acknowledged in the text and in the list of references. This work has not been submitted to any other university or institute of tertiary education in any form. Alice Pollard The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives license. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the license terms of this work. 2 Abstract The prevalence of obesity and associated diseases has increased significantly in the last decade, and is now a major public health concern. It is a significant risk factor for many diseases, including cardiovascular disease (CVD) and type 2 diabetes. Characterised by excess lipid accumulation in the white adipose tissue, which drives many associated pathologies, obesity is caused by chronic, whole-organism energy imbalance; when caloric intake exceeds energy expenditure. Whilst lifestyle changes remain the most effective treatment for obesity and the associated metabolic syndrome, incidence continues to rise, particularly amongst children, placing significant strain on healthcare systems, as well as financial burden.
    [Show full text]