α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UFMG |
| Texto Completo: | https://doi.org/10.1016/j.molmet.2019.06.024 http://hdl.handle.net/1843/44083 https://orcid.org/0000-0002-9484-4145 https://orcid.org/0000-0003-2621-3330 https://orcid.org/0000-0003-4670-919X https://orcid.org/0000-0002-0833-1053 https://orcid.org/0000-0002-9034-5357 https://orcid.org/0000-0002-9870-9469 |
Resumo: | CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior |
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2022-08-09T12:46:09Z2022-08-09T12:46:09Z2019-102891106https://doi.org/10.1016/j.molmet.2019.06.0242212-8778http://hdl.handle.net/1843/44083https://orcid.org/0000-0002-9484-4145https://orcid.org/0000-0003-2621-3330https://orcid.org/0000-0003-4670-919Xhttps://orcid.org/0000-0002-0833-1053https://orcid.org/0000-0002-9034-5357https://orcid.org/0000-0002-9870-9469CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPESP - Fundação de Amparo à Pesquisa do Estado de São PauloObjective: 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.engUniversidade Federal de Minas GeraisUFMGBrasilEEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICAMolecular MetabolismAutofagiaNeuropeptídeosEnzimas proteoliticasJunção neuromuscularMúsculo esqueléticoAutophagyCGRPCalpainNeuromuscular junctionSkeletal muscleα−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated musclesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.sciencedirect.com/science/article/pii/S2212877819302546?via%3Dihub#!Juliano MachadoWilian de Assis SilveiraDawit Albieiro Pinheiro GonçalvesAline Zanatta SchavinskiMuzamil Majid KhanNeusa Maria ZanonMauricio Berriel DiazRüdiger RudolfÍsis do Carmo KettelhutLuiz Carlos Carvalho Navegantesapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/44083/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALα−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction.pdfα−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction.pdfapplication/pdf4367830https://repositorio.ufmg.br/bitstream/1843/44083/2/%ce%b1%e2%88%92Calcitonin%20gene-related%20peptide%20inhibits%20autophagy%20and%20calpain%20systems%20and%20maintains%20the%20stability%20of%20neuromuscular%20junction.pdfdc8767ac9bf3e49ec15835a6b219fe31MD521843/440832022-08-09 09:46:09.661oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2022-08-09T12:46:09Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
| dc.title.pt_BR.fl_str_mv |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| title |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| spellingShingle |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles Juliano Machado Autophagy CGRP Calpain Neuromuscular junction Skeletal muscle Autofagia Neuropeptídeos Enzimas proteoliticas Junção neuromuscular Músculo esquelético |
| title_short |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| title_full |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| title_fullStr |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| title_full_unstemmed |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| title_sort |
α−Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles |
| author |
Juliano Machado |
| author_facet |
Juliano Machado Wilian de Assis Silveira Dawit Albieiro Pinheiro Gonçalves Aline Zanatta Schavinski Muzamil Majid Khan Neusa Maria Zanon Mauricio Berriel Diaz Rüdiger Rudolf Ísis do Carmo Kettelhut Luiz Carlos Carvalho Navegantes |
| author_role |
author |
| author2 |
Wilian de Assis Silveira Dawit Albieiro Pinheiro Gonçalves Aline Zanatta Schavinski Muzamil Majid Khan Neusa Maria Zanon Mauricio Berriel Diaz Rüdiger Rudolf Ísis do Carmo Kettelhut Luiz Carlos Carvalho Navegantes |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Juliano Machado Wilian de Assis Silveira Dawit Albieiro Pinheiro Gonçalves Aline Zanatta Schavinski Muzamil Majid Khan Neusa Maria Zanon Mauricio Berriel Diaz Rüdiger Rudolf Ísis do Carmo Kettelhut Luiz Carlos Carvalho Navegantes |
| dc.subject.por.fl_str_mv |
Autophagy CGRP Calpain Neuromuscular junction Skeletal muscle |
| topic |
Autophagy CGRP Calpain Neuromuscular junction Skeletal muscle Autofagia Neuropeptídeos Enzimas proteoliticas Junção neuromuscular Músculo esquelético |
| dc.subject.other.pt_BR.fl_str_mv |
Autofagia Neuropeptídeos Enzimas proteoliticas Junção neuromuscular Músculo esquelético |
| description |
CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior |
| publishDate |
2019 |
| dc.date.issued.fl_str_mv |
2019-10 |
| dc.date.accessioned.fl_str_mv |
2022-08-09T12:46:09Z |
| dc.date.available.fl_str_mv |
2022-08-09T12:46:09Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/44083 |
| dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1016/j.molmet.2019.06.024 |
| dc.identifier.issn.pt_BR.fl_str_mv |
2212-8778 |
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https://orcid.org/0000-0002-9484-4145 https://orcid.org/0000-0003-2621-3330 https://orcid.org/0000-0003-4670-919X https://orcid.org/0000-0002-0833-1053 https://orcid.org/0000-0002-9034-5357 https://orcid.org/0000-0002-9870-9469 |
| url |
https://doi.org/10.1016/j.molmet.2019.06.024 http://hdl.handle.net/1843/44083 https://orcid.org/0000-0002-9484-4145 https://orcid.org/0000-0003-2621-3330 https://orcid.org/0000-0003-4670-919X https://orcid.org/0000-0002-0833-1053 https://orcid.org/0000-0002-9034-5357 https://orcid.org/0000-0002-9870-9469 |
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2212-8778 |
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eng |
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eng |
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Molecular Metabolism |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
| dc.publisher.department.fl_str_mv |
EEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICA |
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Universidade Federal de Minas Gerais |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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