Version 1
: Received: 16 October 2024 / Approved: 16 October 2024 / Online: 17 October 2024 (11:40:39 CEST)
How to cite:
Park, M.; Cho, S.; Jeong, D. Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in the Ischemia-Reperfusion Injury Model. Preprints2024, 2024101322. https://doi.org/10.20944/preprints202410.1322.v1
Park, M.; Cho, S.; Jeong, D. Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in the Ischemia-Reperfusion Injury Model. Preprints 2024, 2024101322. https://doi.org/10.20944/preprints202410.1322.v1
Park, M.; Cho, S.; Jeong, D. Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in the Ischemia-Reperfusion Injury Model. Preprints2024, 2024101322. https://doi.org/10.20944/preprints202410.1322.v1
APA Style
Park, M., Cho, S., & Jeong, D. (2024). Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in the Ischemia-Reperfusion Injury Model. Preprints. https://doi.org/10.20944/preprints202410.1322.v1
Chicago/Turabian Style
Park, M., Sunghye Cho and Dongtak Jeong. 2024 "Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in the Ischemia-Reperfusion Injury Model" Preprints. https://doi.org/10.20944/preprints202410.1322.v1
Abstract
Cardiac ischemia-reperfusion injury (IRI) occurs when blood flow is restored to the myocardium after a period of ischemia, leading to oxidative stress and subsequent myocardial cell damage, primarily due to the accumulation of reactive oxygen species (ROS). In our previous research, we identified that miR-25 is significantly overexpressed in pressure overload-induced heart failure, and its inhibition improves cardiac function by restoring the expression of SERCA2a, a key protein involved in calcium regulation. In this study, we aimed to investigate the role of miR-25 in the context of ischemia-reperfusion injury.
We found that miR-25 was markedly upregulated under hypoxic conditions in both in vitro and in vivo models. Through in silico analysis, we identified Sestrin3 (SESN3), an antioxidant protein known for its protective effects against oxidative stress, as a novel target of miR-25. Based on these findings, we hypothesized that inhibiting miR-25 would restore Sestrin3 expression, thereby reducing ROS-induced myocardial cell damage and improving cardiac function.
To test this hypothesis, we employed two model systems: a hypoxia/reoxygenation (H/R) stress model using H9c2 myoblasts and a surgically induced ischemia-reperfusion injury mouse model. Our results demonstrated that the use of miR-25 inhibitors significantly improved cardiac function and reduced myocardial damage in both models through the restoration of SESN3 expression.
In conclusion, our findings suggest that targeting miR-25 may serve as a novel therapeutic modality to alleviate oxidative damage in the heart.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
