Angiotensin-(1–9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA pathway
| Autor: | Juan Carlos Roa, Beverly A. Rothermel, Valentina Parra, Alejandro H. Corvalan, Camila López-Crisosto, Pablo E. Morales, Iva Polakovicova, Pablo Rivera-Mejías, César Vásquez-Trincado, María Paz Ocaranza, Hung Ho-Xuan, Vinicius Maracaja-Coutinho, Victor Aliaga-Tobar, Sergio Lavandero, Cristian Sotomayor-Flores, Lorena García, Mario Chiong, Gunter Meister, Christian Pennanen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Dynamins Mitochondrial Dynamics Models Biological Calcium in biology Article Rats Sprague-Dawley 03 medical and health sciences Norepinephrine 0302 clinical medicine Cytosol Animals Myocytes Cardiac Phosphorylation Protein kinase A Molecular Biology NFATC Transcription Factors Chemistry Intracellular Signaling Peptides and Proteins NFAT Cell Biology Hypertrophy Cyclic AMP-Dependent Protein Kinases Protein Kinase A Inhibitor Peptide Fragments Cell biology Mitochondria Up-Regulation MicroRNAs 030104 developmental biology mitochondrial fusion Animals Newborn 030220 oncology & carcinogenesis Mitochondrial fission Calcium Signal transduction Angiotensin I Signal Transduction |
| Zdroj: | Cell Death Differ |
| Popis: | Angiotensin-(1-9) is a peptide from the noncanonical renin-angiotensin system with anti-hypertrophic effects in cardiomyocytes via an unknown mechanism. In the present study we aimed to elucidate it, basing us initially on previous work from our group and colleagues who proved a relationship between disturbances in mitochondrial morphology and calcium handling, associated with the setting of cardiac hypertrophy. Our first finding was that angiotensin-(1-9) can induce mitochondrial fusion through DRP1 phosphorylation. Secondly, angiotensin-(1-9) blocked mitochondrial fission and intracellular calcium dysregulation in a model of norepinephrine-induced cardiomyocyte hypertrophy, preventing the activation of the calcineurin/NFAT signaling pathway. To further investigate angiotensin-(1-9) anti-hypertrophic mechanism, we performed RNA-seq studies, identifying the upregulation of miR-129 under angiotensin-(1-9) treatment. miR-129 decreased the transcript levels of the protein kinase A inhibitor (PKIA), resulting in the activation of the protein kinase A (PKA) signaling pathway. Finally, we showed that PKA activity is necessary for the effects of angiotensin-(1-9) over mitochondrial dynamics, calcium handling and its anti-hypertrophic effects. |
| Databáze: | OpenAIRE |
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