Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/22554
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dc.contributor.authorHamilton, David Leeen_UK
dc.contributor.authorPhilp, Andrewen_UK
dc.contributor.authorMacKenzie, Matthew Gen_UK
dc.contributor.authorPatton, Amyen_UK
dc.contributor.authorTowler, Mhairi Cen_UK
dc.contributor.authorGallagher, Iain Jen_UK
dc.contributor.authorBodine, Sue Cen_UK
dc.contributor.authorBaar, Keithen_UK
dc.date.accessioned2016-09-09T21:24:55Z-
dc.date.available2016-09-09T21:24:55Z-
dc.date.issued2014-08-15en_UK
dc.identifier.urihttp://hdl.handle.net/1893/22554-
dc.description.abstractThe goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. mTen_UK
dc.language.isoenen_UK
dc.publisherAmerican Physiological Societyen_UK
dc.relationHamilton DL, Philp A, MacKenzie MG, Patton A, Towler MC, Gallagher IJ, Bodine SC & Baar K (2014) Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation. American Journal of Physiology - Endocrinology and Metabolism, 307 (4), pp. E365-E373. https://doi.org/10.1152/ajpendo.00674.2013en_UK
dc.rightsLicensed under Creative Commons CC-BY 3.0: the American Physiological Society. Open access publishing allows free access to and distribution of published articles where the author retains copyright of their work by employing a Creative Commons attribution licence. Proper attribution of authorship and correct citation details should be given.en_UK
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_UK
dc.subjectmTORC1en_UK
dc.subjectS6K1en_UK
dc.subjectAMPKen_UK
dc.subjecthypertrophyen_UK
dc.subjectskeletal muscleen_UK
dc.titleMolecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablationen_UK
dc.typeJournal Articleen_UK
dc.identifier.doi10.1152/ajpendo.00674.2013en_UK
dc.identifier.pmid24961241en_UK
dc.citation.jtitleAmerican journal of physiology. Endocrinology and metabolismen_UK
dc.citation.issn1522-1555en_UK
dc.citation.issn0193-1849en_UK
dc.citation.volume307en_UK
dc.citation.issue4en_UK
dc.citation.spageE365en_UK
dc.citation.epageE373en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.author.emaili.j.gallagher@stir.ac.uken_UK
dc.citation.date24/06/2014en_UK
dc.contributor.affiliationSporten_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationUniversity of California, Davisen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationSporten_UK
dc.contributor.affiliationUniversity of California, Davisen_UK
dc.contributor.affiliationUniversity of California, Davisen_UK
dc.identifier.isiWOS:000341709700002en_UK
dc.identifier.scopusid2-s2.0-84908021298en_UK
dc.identifier.wtid584096en_UK
dc.contributor.orcid0000-0002-5620-4788en_UK
dc.contributor.orcid0000-0002-8630-7235en_UK
dc.date.accepted2014-06-19en_UK
dcterms.dateAccepted2014-06-19en_UK
dc.date.filedepositdate2015-11-25en_UK
rioxxterms.apcnot requireden_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorHamilton, David Lee|0000-0002-5620-4788en_UK
local.rioxx.authorPhilp, Andrew|en_UK
local.rioxx.authorMacKenzie, Matthew G|en_UK
local.rioxx.authorPatton, Amy|en_UK
local.rioxx.authorTowler, Mhairi C|en_UK
local.rioxx.authorGallagher, Iain J|0000-0002-8630-7235en_UK
local.rioxx.authorBodine, Sue C|en_UK
local.rioxx.authorBaar, Keith|en_UK
local.rioxx.projectInternal Project|University of Stirling|https://isni.org/isni/0000000122484331en_UK
local.rioxx.freetoreaddate2015-11-25en_UK
local.rioxx.licencehttp://creativecommons.org/licenses/by/4.0/|2015-11-25|en_UK
local.rioxx.filenameHamilton et al_Am J Physiol Endocrinol Metab_2014.pdfen_UK
local.rioxx.filecount1en_UK
local.rioxx.source0193-1849en_UK
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