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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/44083
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dc.creatorJuliano Machadopt_BR
dc.creatorWilian de Assis Silveirapt_BR
dc.creatorDawit Albieiro Pinheiro Gonçalvespt_BR
dc.creatorAline Zanatta Schavinskipt_BR
dc.creatorMuzamil Majid Khanpt_BR
dc.creatorNeusa Maria Zanonpt_BR
dc.creatorMauricio Berriel Diazpt_BR
dc.creatorRüdiger Rudolfpt_BR
dc.creatorÍsis do Carmo Kettelhutpt_BR
dc.creatorLuiz Carlos Carvalho Navegantespt_BR
dc.date.accessioned2022-08-09T12:46:09Z-
dc.date.available2022-08-09T12:46:09Z-
dc.date.issued2019-10-
dc.citation.volume28pt_BR
dc.citation.spage91pt_BR
dc.citation.epage106pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.molmet.2019.06.024pt_BR
dc.identifier.issn2212-8778pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/44083-
dc.description.resumoObjective: Although it is well established that a-calcitonin gene-related peptide (CGRP) stabilizes muscle-type cholinergic receptors nicotinic subunits (AChR), the underlying mechanism by which this neuropeptide regulates muscle protein metabolism and neuromuscular junction (NMJ) morphology is unclear. Methods: To elucidate the mechanisms how CGRP controls NMJ stability in denervated mice skeletal muscles, we carried out physiological, pharmacological, and molecular analyses of atrophic muscles induced by sciatic nerve transection. Results: Here, we report that CGRP treatment in vivo abrogated the deleterious effects on NMJ upon denervation (DEN), an effect that was associated with suppression of skeletal muscle proteolysis, but not stimulation of protein synthesis. CGRP also blocked the DEN-induced increase in endocytic AChR vesicles and the elevation of autophagosomes per NMJ area. The treatment of denervated animals with rapamycin blocked the stimulatory effects of CGRP on mTORC1 and its inhibitory actions on autophagic flux and NMJ degeneration. Furthermore, CGRP inhibited the DEN-induced hyperactivation of Ca2+-dependent proteolysis, a degradative system that has been shown to destabilize NMJ. Consistently, calpain was found to be activated by cholinergic stimulation in myotubes leading to the dispersal of AChR clusters, an effect that was abolished by CGRP. Conclusion: Taken together, these data suggest that the inhibitory effect of CGRP on autophagy and calpain may represent an important mechanism for the preservation of synapse morphology when degradative machinery is exacerbated upon denervation conditions.pt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentEEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofMolecular Metabolismpt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectAutophagypt_BR
dc.subjectCGRPpt_BR
dc.subjectCalpainpt_BR
dc.subjectNeuromuscular junctionpt_BR
dc.subjectSkeletal musclept_BR
dc.subject.otherAutofagiapt_BR
dc.subject.otherNeuropeptídeospt_BR
dc.subject.otherEnzimas proteoliticaspt_BR
dc.subject.otherJunção neuromuscularpt_BR
dc.subject.otherMúsculo esqueléticopt_BR
dc.titleα−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated musclespt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.sciencedirect.com/science/article/pii/S2212877819302546?via%3Dihub#!pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-9484-4145pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-2621-3330pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-4670-919Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-0833-1053pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-9034-5357pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-9870-9469pt_BR
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