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Ramelteon alleviates myocardial ischemia/reperfusion injury (MIRI) through Sirt3--dependent regulation of cardiomyocyte apoptosis.
Yang, Zhenbo; Xie, Yilin; Li, Mengyang; Chen, Wenxian; Zhong, Changsheng; Ju, Jin; Deng, Qin; Wang, Huifang; Cheng, Ting; Zhang, Lei; Du, Weijie; Liang, Haihai.
Afiliación
  • Yang Z; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China; The Academician Cooperative Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 511400, China.
  • Xie Y; School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Li M; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Chen W; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Zhong C; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Ju J; The Academician Cooperative Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 511400, China.
  • Deng Q; School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Wang H; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Cheng T; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Zhang L; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • Du W; Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research,Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2
  • Liang H; Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, Guangdong, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pha
Biomed Pharmacother ; 172: 116229, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38330708
ABSTRACT
Reperfusion stands as a pivotal intervention for ischemic heart disease. However, the restoration of blood flow to ischemic tissue always lead to further damage, which is known as myocardial ischemia/reperfusion injury (MIRI). Ramelteon is an orally administered drug used to improve sleep quality, which is famous for its high bioadaptability and absence of notable addictive characteristics. However, the specific mechanism by which it improves MIRI is still unclear. Sirtuin-3 (Sirt3), primarily located in mitochondria, is crucial in mitigating many cardiac diseases, including MIRI. Based on the structure of Sirt3, we simulated molecular docking and identified several potential amino acid binding sites between it and ramelteon. Therefore, we propose a hypothesis that ramelteon may exert cardioprotective effects by activating the Sirt3 signaling pathway. Our results showed that the activation levels and expression level of Sirt3 were significantly decreased in MIRI tissue and H2O2 stimulated H9C2 cells, while ramelteon treatment upregulated Sirt3 activity and expression. After treat with 3-TYP, a classic Sirt3 activity inhibitor, we constructed myocardial ischemia/reperfusion surgery in vivo and induced H9C2 cells with H2O2 in vitro. The results showed that the myocardial protection and anti-apoptotic effects of ramelteon were antagonized by 3-TYP, indicating that the activation of Sirt3 is a key mechanism for ramelteon to exert myocardial protection. In summary, our results confirm a novel mechanism by which ramelteon improves MIRI by activating Sirt3 signaling pathway, providing strong evidence for the treatment of MIRI with ramelteon.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión Miocárdica / Isquemia Miocárdica / Sirtuina 3 / Indenos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión Miocárdica / Isquemia Miocárdica / Sirtuina 3 / Indenos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia