title: Divergent regulation of insulin-like growth factor binding protein genes in cultured Atlantic salmon myotubes under different models of catabolism and anabolism.
abstract: Much attention has been given to insulin-like growth factor (Igf) pathways that regulate the balance of skeletal muscle protein synthesis and breakdown in response to a range of extrinsic and intrinsic signals. However, we have a less complete understanding of how the same signals modulate muscle mass upstream of such signalling, through a family of functionally-diverse Igf-binding proteins (Igfbps) that modify the availability of Igfs to the cell receptor Igf1r. We exposed cultured myotubes from Atlantic salmon (Salmo salar L.) to treatments recapturing three catabolic signals: inflammation (interleukin-1β), stress (dexamethasone) and fasting (amino acid deprivation), plus one anabolic signal: recovery of muscle mass post-fasting (supplementation of fasted myotubes with Igf-I and amino acids). The intended phenotype of treatments was confirmed by significant changes in myotube diameter and immunofluorescent staining of structural proteins. We quantified the mRNA-level regulation of the full expressed Igf and Igfbp gene complement across a post-treatment time course, along with marker genes for muscle structural protein synthesis, as well as muscle breakdown, via the ubiquitin-proteasome and autophagy systems. Our results highlight complex, non-overlapping responses of Igfbp family members to the different treatments, suggesting that the profile of expressed Igfbps is differentially regulated by distinct signals promoting similar muscle remodelling phenotypes. We also demonstrate divergent regulation of salmonid-specific gene duplicates of igfbp5b1 and igfbp5b2 under distinct catabolic and anabolic conditions. Overall, this study increases our understanding of the regulation of Igfbp genes in response to signals that promote remodelling of skeletal muscle.
authors.affiliation: School of Biology, Scottish Oceans Institute, University of St Andrews, Fife KY16 8LB, Scotland, United Kingdom. Electronic address: dgdlsc@st-andrews.ac.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Garcia de la Serrana
authors.affiliation: School of Biology, Scottish Oceans Institute, University of St Andrews, Fife KY16 8LB, Scotland, United Kingdom; Interdisciplinary Center for Aquaculture Research (INCAR), Víctor Lamas 1290, PO Box 160-C, Concepción, Chile; Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, Scotland, United Kingdom.
authors.forename: Eduardo N
authors.initials: EN
authors.lastname: Fuentes
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, Scotland, United Kingdom.
authors.forename: Samuel A M
authors.initials: SAM
authors.lastname: Martin
authors.affiliation: School of Biology, Scottish Oceans Institute, University of St Andrews, Fife KY16 8LB, Scotland, United Kingdom.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Johnston
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, Scotland, United Kingdom. Electronic address: daniel.macqueen@abdn.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Macqueen
mesh_terms: D000596:Amino Acids / Q000172:deficiency; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D016014:Linear Models; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020317:Salmo salar / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000596:Amino Acids; D018969:Insulin-Like Growth Factor Binding Proteins; D053583:Interleukin-1beta; D009124:Muscle Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone
keywords: Amino acids; Atlantic salmon; Cell culture; Dexamethasone; Igf binding proteins; Insulin-like growth factor system; Interleukin-1β; Myotubes; Skeletal muscle