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  • NPPA/atrial natriuretic peptide is an extracellular modulator of autophagy in the heart.

NPPA/atrial natriuretic peptide is an extracellular modulator of autophagy in the heart.

Autophagy (2022-08-24)
Maurizio Forte, Simona Marchitti, Flavio Di Nonno, Rosita Stanzione, Leonardo Schirone, Maria Cotugno, Franca Bianchi, Sonia Schiavon, Salvatore Raffa, Danilo Ranieri, Salvatore Fioriniello, Floriana Della Ragione, Maria Rosaria Torrisi, Roberto Carnevale, Valentina Valenti, Francesco Versaci, Giacomo Frati, Carmine Vecchione, Massimo Volpe, Speranza Rubattu, Sebastiano Sciarretta
ABSTRACT

NPPA/atrial natriuretic peptide (natriuretic peptide type A) exerts critical pleiotropic effects in the cardiovascular system, limiting cardiomyocyte hypertrophy and death, reducing cardiac fibrosis and promoting vascular integrity. However, the molecular mechanisms underlying these beneficial effects still need to be clarified. We demonstrated for the first time that macroautophagy/autophagy is involved in the local protective effects of NPPA in cardiomyocytes (CMs), both in vitro and in vivo. Exogenous NPPA rapidly activates autophagy in CMs through NPR1/type A natriuretic peptide receptor and PRKG/protein kinase G signaling and also increases cardiac autophagy in mice. Remarkably, endogenous NPPA is secreted by CMs in response to glucose deprivation or hypoxia, thereby stimulating autophagy through autocrine/paracrine mechanisms. NPPA preserves cell viability and reduces hypertrophy in response to stress through autophagy activation. In vivo, we found that Nppa knockout mice undergoing ischemia-reperfusion (I/R) show increased infarct size and reduced autophagy. Reactivation of autophagy by Tat-Beclin D11 limits I/R injury. We also found that the protective effects of NPPA in reducing infarct size are abrogated in the presence of autophagy inhibition. Mechanistically, we found that NPPA stimulates autophagy through the activation of TFEB (transcription factor EB). Our data suggest that NPPA is a novel extracellular regulator of autophagy in the heart.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Glycine, suitable for electrophoresis, ≥99%
Sigma-Aldrich
Normal Goat IgG, This Normal Goat IgG is validated for use in ELISA Flow Cytometry Immunoblotting Immunofluorescence Immunohistochemistry Immunoprecipitation for the detection of Goat IgG, Non-immune.
Sigma-Aldrich
Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC)
Sigma-Aldrich
Goat Anti-Mouse IgG, H&L Chain Specific Peroxidase Conjugate, liquid, Calbiochem®
Sigma-Aldrich
Anti-phospho TFEB (Ser142), from rabbit, purified by affinity chromatography