Fuziline alleviates isoproterenol‐induced myocardial injury by inhibiting ROS‐triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathway
Open Access
- 7 December 2019
- journal article
- research article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 24 (2), 1332-1344
- https://doi.org/10.1111/jcmm.14803
Abstract
Fuziline, an aminoalcohol‐diterpenoid alkaloid derived fromAconiti lateralisradix preparata, has been reported to have a cardioprotective activity in vitro. However, the potential mechanism of fuziline on myocardial protection remains unknown. In this study, we aimed to explore the efficacy and mechanism of fuziline on isoproterenol (ISO)‐induced myocardial injury in vitro and in vivo. As a result, fuziline effectively increased cell viability and alleviated ISO‐induced apoptosis. Meanwhile, fuziline significantly decreased the production of ROS, maintained mitochondrial membrane potential (MMP) and blocked the release of cytochrome C, suggesting that fuziline could play the cardioprotective role through restoring the mitochondrial function. Fuziline also could suppress ISO‐induced endoplasmic reticulum (ER) stress via the PERK/eIF2α/ATF4/Chop pathway. In addition, using ROS scavenger NAC could decrease ISO‐induced apoptosis and block ISO‐induced ER stress, while PERK inhibitor GSK2606414 did not reduce the production of ROS, indicating that excess production of ROS induced by ISO triggered ER stress. And fuziline protected against ISO‐induced myocardial injury by inhibiting ROS‐triggered ER stress. Furthermore, fuziline effectively improved cardiac function on ISO‐induced myocardial injury in rats. Western blot analysis also showed that fuziline reduced ER stress‐induced apoptosis in vivo. Above these results demonstrated that fuziline could reduce ISO‐induced myocardial injury in vitro and in vivo by inhibiting ROS‐triggered ER stress via the PERK/eIF2α/ATF4/Chop pathway.Keywords
Funding Information
- National Major Scientific and Program of Introducing Talents of Discipline to Universities (B13038)
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