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

Animals Autophagy / drug effects Calcitonin Gene-Related Peptide / pharmacology Calpain / antagonists & inhibitors Male Mice Mice, Inbred C57BL Muscle, Skeletal / drug effects Neuromuscular Junction / drug effects Vasodilator Agents / pharmacology
Autophagy CGRP Calpain Neuromuscular junction Skeletal muscle

Journal

Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730

Informations de publication

Date de publication:
10 2019
Historique:
received: 20 03 2019
revised: 23 06 2019
accepted: 28 06 2019
pubmed: 25 7 2019
medline: 23 6 2020
entrez: 24 7 2019
Statut: ppublish

Résumé

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. 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. 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 Ca 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.

Identifiants

DOI: 10.1016/j.molmet.2019.06.024 PMID: 31331823 PMC: PMC6822259
pubmed: 31331823
pii: S2212-8778(19)30254-6
doi: 10.1016/j.molmet.2019.06.024
pmc: PMC6822259
pii:
doi:

Substances chimiques

Vasodilator Agents 0
Calpain EC 3.4.22.-
Calcitonin Gene-Related Peptide JHB2QIZ69Z

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

91-106

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.

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Auteurs

Juliano Machado (J)

Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Biochemistry/Immunology, Ribeirão Preto Medical School/University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120, Heidelberg, Germany. Electronic address: juliano.machado@helmholtz-muenchen.de.

Wilian A Silveira (WA)

Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: silveira.wa@gmail.com.

Dawit A Gonçalves (DA)

Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Biochemistry/Immunology, Ribeirão Preto Medical School/University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: dawit@ufmg.br.

Aline Zanatta Schavinski (AZ)

Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: alinezanatta@usp.br.

Muzamil M Khan (MM)

Institute of Molecular and Cell Biology, University of Applied Sciences Mannheim, Mannheim, Germany; Institute of Medical Technology, University of Heidelberg and University of Applied Sciences Mannheim, Mannheim, Germany. Electronic address: muzamil.m.khan@embl.de.

Neusa M Zanon (NM)

Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: neuzanon@yahoo.com.br.

Mauricio Berriel Diaz (MB)

Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120, Heidelberg, Germany. Electronic address: mauricio.berrieldiaz@helmholtz-muenchen.de.

Rüdiger Rudolf (R)

Institute of Molecular and Cell Biology, University of Applied Sciences Mannheim, Mannheim, Germany; Institute of Medical Technology, University of Heidelberg and University of Applied Sciences Mannheim, Mannheim, Germany. Electronic address: r.rudolf@hs-mannheim.de.

Isis C Kettelhut (IC)

Department of Biochemistry/Immunology, Ribeirão Preto Medical School/University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: idckette@fmrp.usp.br.

Luiz C Navegantes (LC)

Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: navegantes@fmrp.com.br.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Autophagie › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Neuropeptides › Peptide relié au gène de la calcitonine › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Endopeptidases › Cysteine endopeptidases › Calpain › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Muscles squelettiques › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › Synapse neuro-effectrice › Jonction neuromusculaire › α-Calcitonin gene-related peptide inhibits...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents cardiovasculaires › Vasodilatateurs › α-Calcitonin gene-related peptide inhibits...