α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles

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dc.creatorJuliano Machado
dc.creatorWilian de Assis Silveira
dc.creatorDawit Albieiro Pinheiro Gonçalves
dc.creatorAline Zanatta Schavinski
dc.creatorMuzamil Majid Khan
dc.creatorNeusa Maria Zanon
dc.creatorMauricio Berriel Diaz
dc.creatorRüdiger Rudolf
dc.creatorÍsis do Carmo Kettelhut
dc.creatorLuiz Carlos Carvalho Navegantes
dc.date.accessioned2022-08-09T12:46:09Z
dc.date.accessioned2025-09-08T23:25:42Z
dc.date.available2022-08-09T12:46:09Z
dc.date.issued2019-10
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.molmet.2019.06.024
dc.identifier.issn2212-8778
dc.identifier.urihttps://hdl.handle.net/1843/44083
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofMolecular Metabolism
dc.rightsAcesso Aberto
dc.subjectAutofagia
dc.subjectNeuropeptídeos
dc.subjectEnzimas proteoliticas
dc.subjectJunção neuromuscular
dc.subjectMúsculo esquelético
dc.subject.otherAutophagy
dc.subject.otherCGRP
dc.subject.otherCalpain
dc.subject.otherNeuromuscular junction
dc.subject.otherSkeletal muscle
dc.titleα−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles
dc.typeArtigo de periódico
local.citation.epage106
local.citation.spage91
local.citation.volume28
local.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.
local.identifier.orcidhttps://orcid.org/0000-0002-9484-4145
local.identifier.orcidhttps://orcid.org/0000-0003-2621-3330
local.identifier.orcidhttps://orcid.org/0000-0003-4670-919X
local.identifier.orcidhttps://orcid.org/0000-0002-0833-1053
local.identifier.orcidhttps://orcid.org/0000-0002-9034-5357
local.identifier.orcidhttps://orcid.org/0000-0002-9870-9469
local.publisher.countryBrasil
local.publisher.departmentEEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S2212877819302546?via%3Dihub#!

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