Calcitonin gene-related peptide exerts inhibitory effects on autophagy in the heart of mice

Autor(es)

Schavinski, Aline Zanatta ^[1] ; Machado, Juliano ^[2] ; Novaes Morgan, Henrique Jorge ^[1] ; Lautherbach, Natalia ^[3] ; Paula-Gomes, Silvia ^[4] ; Kettelhut, Isis C. ^{[1, 3]} ; Navegantes, Luiz Carlos C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Helmholtz Zentrum Munchen, Inst Diabet & Canc, German Res Ctr Environm Hlth, Munich - Germany

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem Immunol, Ribeirao Preto, SP - Brazil

^[4] Univ Fed Ouro Preto, Dept Biol Sci, Ouro Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Peptides; v. 146, DEC 2021.
• Citações Web of Science: 0

Resumo

Calcitonin Gene-Related Peptide (CGRP) is a potent vasodilator peptide widely distributed in the central nervous system and various peripheral tissues, including cardiac muscle. However, its role in heart protein metabolism remains unknown. We examined the acute effects of CGRP on autophagy and the related signaling pathways in the heart mice and cultured neonatal cardiomyocytes. CGRP (100 mu g kg-1; s.c.) or 0.9 % saline was injected in awake male C57B16 mice, and the metabolic profile was determined up to 60 min. In fed mice, CGRP drastically increased glycemia and reduced insulinemia, an effect that was accompanied by reduced cardiac phosphorylation levels of Akt at Ser473 without affecting FoxO. Despite these catabolic effects, CGRP acutely inhibited autophagy as estimated by the decrease in LC3II:LC3I and autophagic flux. In addition, the fasting-induced autophagic flux in mice hearts was entirely abrogated by one single injection of CGRP. In parallel, CGRP stimulated PKA/CREB and mTORC1 signaling and increased the phosphorylation of Unc51-like kinase-1 (ULK1), an essential protein in autophagy initiation. Similar effects were observed in cardiomyocytes, in which CGRP also inhibited autophagic flux and stimulated Akt and FoxO phosphorylation. These findings suggest that CGRP in vivo acutely suppresses autophagy in the heart of fed and fasted mice, most likely through the activation of PKA/ mTORC1 signaling but independent of Akt. (AU)

• Processo FAPESP: 18/10089-2 - Controle neural, hormonal e nutricional da autofagia
• Beneficiário: Isis Do Carmo Kettelhut
• Modalidade de apoio: Auxílio à Pesquisa - Temático