Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model
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 th...
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MDPI AG
2025-01-01
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| Series: | Antioxidants |
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| author | Mina Park Sunghye Cho Dongtak Jeong |
| author_facet | Mina Park Sunghye Cho Dongtak Jeong |
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| description | 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. |
| format | Article |
| id | doaj-art-d7a269a6b8584380882fc96617d5fc8c |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-d7a269a6b8584380882fc96617d5fc8c2025-01-24T13:19:21ZengMDPI AGAntioxidants2076-39212025-01-011416110.3390/antiox14010061Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury ModelMina Park0Sunghye Cho1Dongtak Jeong2Department of Medicinal & Life Science, College of Science and Convergence Technology, Hanyang University—ERICA, Ansan 15588, Republic of KoreaDepartment of Medicinal & Life Science, College of Science and Convergence Technology, Hanyang University—ERICA, Ansan 15588, Republic of KoreaDepartment of Medicinal & Life Science, College of Science and Convergence Technology, Hanyang University—ERICA, Ansan 15588, Republic of KoreaCardiac 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.https://www.mdpi.com/2076-3921/14/1/61ischemia–reperfusion injurysestrinmiR-25ROSoxidative damageapoptosis |
| spellingShingle | Mina Park Sunghye Cho Dongtak Jeong Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model Antioxidants ischemia–reperfusion injury sestrin miR-25 ROS oxidative damage apoptosis |
| title | Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model |
| title_full | Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model |
| title_fullStr | Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model |
| title_full_unstemmed | Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model |
| title_short | Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia–Reperfusion Injury Model |
| title_sort | restoration of sestrin 3 expression mitigates cardiac oxidative damage in ischemia reperfusion injury model |
| topic | ischemia–reperfusion injury sestrin miR-25 ROS oxidative damage apoptosis |
| url | https://www.mdpi.com/2076-3921/14/1/61 |
| work_keys_str_mv | AT minapark restorationofsestrin3expressionmitigatescardiacoxidativedamageinischemiareperfusioninjurymodel AT sunghyecho restorationofsestrin3expressionmitigatescardiacoxidativedamageinischemiareperfusioninjurymodel AT dongtakjeong restorationofsestrin3expressionmitigatescardiacoxidativedamageinischemiareperfusioninjurymodel |