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dc.contributor.authorHulmi, Juha
dc.contributor.authorHentilä, Jaakko
dc.contributor.authorDeRuisseau, Keith C.
dc.contributor.authorOliveira, Bernardo M.
dc.contributor.authorPapaioannou, Konstantinos G.
dc.contributor.authorAutio, Reija
dc.contributor.authorKujala, Urho
dc.contributor.authorRitvos, Olli
dc.contributor.authorKainulainen, Heikki
dc.contributor.authorKorkmaz, Ayhan
dc.contributor.authorAtalay, Mustafa
dc.date.accessioned2016-08-30T07:52:53Z
dc.date.available2017-08-20T21:45:09Z
dc.date.issued2016
dc.identifier.citationHulmi, J., Hentilä, J., DeRuisseau, K. C., Oliveira, B. M., Papaioannou, K. G., Autio, R., Kujala, U., Ritvos, O., Kainulainen, H., Korkmaz, A., & Atalay, M. (2016). Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress. <i>Free Radical Biology and Medicine</i>, <i>99</i>(October), 308-322. <a href="https://doi.org/10.1016/j.freeradbiomed.2016.08.017" target="_blank">https://doi.org/10.1016/j.freeradbiomed.2016.08.017</a>
dc.identifier.otherCONVID_26176199
dc.identifier.otherTUTKAID_70970
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/51129
dc.description.abstractProtein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, a model of DMD, under basal conditions and in response to seven weeks of voluntary exercise and/or activin receptor IIB ligand blocking using soluble activin receptor-Fc (sAcvR2B-Fc) administration. In conjunction with reduced muscle strength, mdx muscle displayed greater levels of UPR/ER-pathway indicators including greater protein levels of IRE1α, PERK and Atf6b mRNA. Downstream to IRE1α and PERK, spliced Xbp1 mRNA and phosphorylation of eIF2α, were also increased. Most of the cytoplasmic and ER chaperones and mitochondrial UPR markers were unchanged in mdx muscle. Oxidized glutathione was greater in mdx and was associated with increases in lysine acetylated proteome and phosphorylated sirtuin 1. Exercise increased oxidative stress when performed independently or combined with sAcvR2B-Fc administration. Although neither exercise nor sAcvR2B-Fc administration imparted a clear effect on ER stress/UPR pathways or heat shock proteins, sAcvR2B-Fc administration increased protein expression levels of GRP78/BiP, a triggering factor for ER stress/UPR activation and TxNIP, a redox-regulator of ER stress-induced inflammation. In conclusion, the ER stress and UPR are increased in mdx muscle. However, these processes are not distinctly improved by voluntary exercise or blocking activin receptor IIB ligands and thus do not appear to be optimal therapeutic choices for improving proteostasis in DMD.
dc.language.isoeng
dc.publisherElsevier Inc.; Society for Free Radical Biology and Medicine
dc.relation.ispartofseriesFree Radical Biology and Medicine
dc.subject.othermyostatin
dc.subject.othermdx
dc.subject.otherER-stress
dc.subject.otherUPR
dc.titleEffects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201608303908
dc.contributor.laitosLiikuntabiologian laitosfi
dc.contributor.laitosTerveystieteiden laitosfi
dc.contributor.laitosDepartment of Biology of Physical Activityen
dc.contributor.laitosDepartment of Health Sciencesen
dc.contributor.oppiaineLiikuntafysiologiafi
dc.contributor.oppiaineLiikuntalääketiedefi
dc.contributor.oppiaineExercise Physiologyen
dc.contributor.oppiaineSports and Exercise Medicineen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2016-08-30T06:15:14Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerange308-322
dc.relation.issn0891-5849
dc.relation.numberinseriesOctober
dc.relation.volume99
dc.type.versionacceptedVersion
dc.rights.copyright© 2016 Elsevier Inc. This is a final draft version of an article whose final and definitive form has been published by Elsevier. Published in this repository with the kind permission of the publisher.
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber275922
dc.relation.doi10.1016/j.freeradbiomed.2016.08.017
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramAkatemiatutkija, SAfi
jyx.fundingprogramAcademy Research Fellow, AoFen
jyx.fundinginformationThis work was supported by Academy of Finland (Decision no. 137787 and no. 275922 to JJH and decision no. 134117 to RA) and the Finnish Cultural Foundation (HA) and Paulo Foundation (HK).


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