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http://hdl.handle.net/2445/185168
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DC Field | Value | Language |
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dc.contributor.author | Montori Grau, Marta | - |
dc.contributor.author | Aguilar, David | - |
dc.contributor.author | Zarei, Mohammad | - |
dc.contributor.author | Pizarro Delgado, Javier | - |
dc.contributor.author | Palomer Tarridas, Francesc Xavier | - |
dc.contributor.author | Vázquez Carrera, Manuel | - |
dc.date.accessioned | 2022-04-28T12:28:35Z | - |
dc.date.available | 2022-04-28T12:28:35Z | - |
dc.date.issued | 2022-04-15 | - |
dc.identifier.issn | 1478-811X | - |
dc.identifier.uri | http://hdl.handle.net/2445/185168 | - |
dc.description.abstract | Background Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) downregulation in skeletal muscle contributes to insulin resistance and type 2 diabetes mellitus. Here, we examined the effects of endoplasmic reticulum (ER) stress on PGC-1α levels in muscle and the potential mechanisms involved. Methods The human skeletal muscle cell line LHCN-M2 and mice exposed to different inducers of ER stress were used. Results Palmitate- or tunicamycin-induced ER stress resulted in PGC-1α downregulation and enhanced expression of activating transcription factor 4 (ATF4) in human myotubes and mouse skeletal muscle. Overexpression of ATF4 decreased basal PCG-1α expression, whereas ATF4 knockdown abrogated the reduction of PCG-1α caused by tunicamycin in myotubes. ER stress induction also activated mammalian target of rapamycin (mTOR) in myotubes and reduced the nuclear levels of cAMP response element-binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), a positive modulator of PGC-1α transcription. The mTOR inhibitor torin 1 restored PCG-1α and CRTC2 protein levels. Moreover, siRNA against S6 kinase, an mTORC1 downstream target, prevented the reduction in the expression of CRTC2 and PGC-1α caused by the ER stressor tunicamycin. Conclusions Collectively, these findings demonstrate that ATF4 and the mTOR-CRTC2 axis regulates PGC-1α transcription under ER stress conditions in skeletal muscle, suggesting that its inhibition might be a therapeutic target for insulin resistant states. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/s12964-022-00865-9 | - |
dc.relation.ispartof | Cell Communication and Signaling, 2022, vol. 20, p. 53 | - |
dc.relation.uri | https://doi.org/10.1186/s12964-022-00865-9 | - |
dc.rights | cc-by (c) Montori Grau, Marta et al., 2022 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Reticle endoplasmàtic | - |
dc.subject.classification | Diabetis | - |
dc.subject.classification | Resistència a la insulina | - |
dc.subject.other | Endoplasmic reticulum | - |
dc.subject.other | Diabetes | - |
dc.subject.other | Insulin resistance | - |
dc.title | Endoplasmic reticulum stress downregulates PGC-1α in skeletal muscle through ATF4 and an mTOR-mediated reduction of CRTC2 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 723069 | - |
dc.date.updated | 2022-04-28T12:28:36Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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723069.pdf | 2.38 MB | Adobe PDF | View/Open |
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