Sotomayor-Flores, Cristian and Rivera-Mejias, Pablo and Vasquez-Trincado, Cesar and Lopez-Crisosto, Camila and Morales, Pablo E. and Pennanen, Christian and Polakovicova, Iva and Aliaga-Tobar, Victor and Garcia, Lorena and Roa, Juan Carlos and Rothermel, Beverly A. and Maracaja-Coutinho, Vinicius and Ho-Xuan, Hung and Meister, Gunter and Chiong, Mario and Ocaranza, Maria Paz and Corvalan, Alejandro H. and Parra, Valentina and Lavandero, Sergio (2020) Angiotensin-(1-9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA pathway. CELL DEATH AND DIFFERENTIATION, 27 (9). pp. 2586-2604. ISSN 1350-9047, 1476-5403
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEPENDENT PROTEIN-KINASE; CARDIAC-HYPERTROPHY; MICRORNAS; FISSION; FUSION; DRP1; PHOSPHORYLATION; TRANSLOCATION; INHIBITION; EXPRESSION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 08:42 |
| Last Modified: | 29 Mar 2021 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44952 |
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