Abscisic Acid and Its Receptors LANCL1 and LANCL2 Control Cardiomyocyte Mitochondrial Function, Expression of Contractile, Cytoskeletal and Ion Channel Proteins and Cell Proliferation via ERRα
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Published:2023-08-30
Issue:9
Volume:12
Page:1692
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ISSN:2076-3921
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Container-title:Antioxidants
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language:en
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Short-container-title:Antioxidants
Author:
Spinelli Sonia1ORCID, Guida Lucrezia2, Passalacqua Mario2ORCID, Magnone Mirko2, Cossu Vanessa34, Sambuceti Gianmario45ORCID, Marini Cecilia46, Sturla Laura2ORCID, Zocchi Elena2
Affiliation:
1. Laboratorio di Nefrologia Molecolare, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy 2. Section Biochemistry, Department of Experimental Medicine (DIMES), University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy 3. Section Human Anatomy, Department of Experimental Medicine (DIMES), University of Genova, 16126 Genova, Italy 4. U.O. Medicina Nucleare, IRCCS Ospedale Policlinico San Martino, 16131 Genova, Italy 5. Department of Health Sciences, University of Genoa, 16132 Genova, Italy 6. Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 20100 Milan, Italy
Abstract
The cross-kingdom stress hormone abscisic acid (ABA) and its mammalian receptors LANCL1 and LANCL2 regulate the response of cardiomyocytes to hypoxia by activating NO generation. The overexpression of LANCL1/2 increases transcription, phosphorylation and the activity of eNOS and improves cell vitality after hypoxia/reoxygenation via the AMPK/PGC-1α axis. Here, we investigated whether the ABA/LANCL system also affects the mitochondrial oxidative metabolism and structural proteins. Mitochondrial function, cell cycle and the expression of cytoskeletal, contractile and ion channel proteins were studied in H9c2 rat cardiomyoblasts overexpressing or silenced by LANCL1 and LANCL2, with or without ABA. Overexpression of LANCL1/2 significantly increased, while silencing conversely reduced the mitochondrial number, OXPHOS complex I, proton gradient, glucose and palmitate-dependent respiration, transcription of uncoupling proteins, expression of proteins involved in cytoskeletal, contractile and electrical functions. These effects, and LANCL1/2-dependent NO generation, are mediated by transcription factor ERRα, upstream of the AMPK/PGC1-α axis and transcriptionally controlled by the LANCL1/2–ABA system. The ABA-LANCL1/2 hormone-receptor system controls fundamental aspects of cardiomyocyte physiology via an ERRα/AMPK/PGC-1α signaling axis and ABA-mediated targeting of this axis could improve cardiac function and resilience to hypoxic and dysmetabolic conditions.
Funder
University of Genova
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology
Reference65 articles.
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