RT Journal Article
T1 miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury.
A1 Toro, Rocio
A1 Perez-Serra, Alexandra
A1 Mangas, Alipio
A1 Campuzano, Oscar
A1 Sarquella-Brugada, Georgia
A1 Quezada-Feijoo, Maribel
A1 Ramos, Monica
A1 Alcala, Martin
A1 Carrera, Esther
A1 Garcia-Padilla, Carlos
A1 Franco, Diego
A1 Bonet, Fernando
K1 ATF6
K1 Endoplasmic reticulum stress
K1 Ischemic dilated cardiomyopathy
K1 miR-16-5p
K1 Reactive oxygen species
AB Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidative stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative stress-induced injury.
PB MDPI
YR 2022
FD 2022-01-15
LK http://hdl.handle.net/10668/21134
UL http://hdl.handle.net/10668/21134
LA en
NO Toro R, Pérez-Serra A, Mangas A, Campuzano O, Sarquella-Brugada G, Quezada-Feijoo M, et al. miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury. Int J Mol Sci. 2022 Jan 18;23(3):1036
DS RISalud
RD Apr 9, 2025