title: Regulatory factors controlling muscle mass: Competition between innate immune function and anabolic signals in regulation of atrogin-1 in Atlantic salmon.
abstract: Atrogin-1 is a conserved ubiquitin E3 ligase that is central to the early stages of skeletal and cardiac muscle wasting and degradation following starvation and inflammatory diseases. The control of protein turnover is different between endothermic and ectothermic animals reflecting the body energy requirements. Here we have characterised the promoter of the atrogin-1 gene in a phylogenetically diverse group of vertebrates and show conserved FOXO elements are present in all species examined. We have examined the gene expression responses in primary muscle cell culture to key immune modulators (IL-1β, interferon type 1 and interferon γ) and to the anabolic hormone insulin like growth factor (IGF-1). We show that the IL-1β and interferon type 1 increased atrogin-1 mRNA expression whereas IGF-1 suppressed atrogin-1 expression. The proximal promoter of salmon atrogin-1 was used to transfect primary muscle cell cultures and we found all three cytokines increased promoter activity whereas there was a decrease caused by IGF-1 exposure. We hypothesise that the main drivers for atrogin-1 expression are via the conserved FOXO site, but other transcription binding sites such as NFκB, STAT and IRFs may also be involved in a synergistic manner following immune stimulation when free amino acids need to be released for muscle protein reserves.
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK.
authors.forename: Zeynab
authors.initials: Z
authors.lastname: Heidari
authors.affiliation: BioMar Ltd., Grangemouth Docks, Grangemouth FK3 8UL, UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Bickerdike
authors.affiliation: BioMar Ltd., Grangemouth Docks, Grangemouth FK3 8UL, UK.
authors.forename: John
authors.initials: J
authors.lastname: Tinsley
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK.
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.affiliation: Institute of Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan, ROC.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Institute of Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan, ROC.
authors.forename: Tzong-Yueh
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK. Electronic address: Sam.martin@abdn.ac.uk.
authors.forename: Samuel A M
authors.initials: SA
authors.lastname: Martin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000494:pharmacology; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D007113:Immunity, Innate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020317:Salmo salar / Q000235:genetics / Q000276:immunology*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016207:Cytokines; D044783:F-Box Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D008156:Luciferases
keywords: Atlantic salmon; Atrogin-1; Gene expression; Muscle cell culture; Promoter analysis