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Swimming training attenuates doxorubicin induced cardiomyopathy by targeting the mir-17-3p/KEAP1/NRF2 axis.
Gao, Yefei; Ling, Yan; Wu, Haowei; Zhang, Peipei; Zhou, Jiedong; Gu, Haodi; Yang, Juntao; Zhou, Yan; Zhong, Zuoquan; Chi, Jufang.
Afiliación
  • Gao Y; Department of Cardiology, The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Ling Y; The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Wu H; Department of Cardiology, The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Zhang P; The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Zhou J; The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Gu H; The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Yang J; Department of Cardiology, The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
  • Zhou Y; Department of Cardiology, The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China. Electronic address: zhouzhou331301@sina.com.
  • Zhong Z; The First Affiliated Hospital of ShaoXing University, Shaoxing University, Shaoxing, 312000, Zhejiang, China. Electronic address: 806273054@qq.com.
  • Chi J; Department of Cardiology, Zhuji People's Hospital, Zhejiang, China. Electronic address: chijf@usx.edu.cn.
Biochem Biophys Res Commun ; 739: 150568, 2024 Aug 19.
Article en En | MEDLINE | ID: mdl-39178797
ABSTRACT
Doxorubicin (DOX), as a first-line anticancer drug, is widely used in the treatment of various cancers. However, its clinical application is restricted due to its severe cardiac toxicity. Previous studies have indicated exercise training can alleviate the DOX-induced cardiotoxicity (DIC), but the underlying mechanism remains unclear. Our research has discovered, post-exercise, an elevated expression level of mir-17-3p, but in DIC its level decreases. Therefore, we further studied the effect of exercise mir-17-3p axis on DIC. In vivo, we simulated DIC mouse model, followed by an intervention using swimming and adenovirus to inhibit mir-17-3p. We found that inhibition of mir-17-3p can weaken the protection of exercise against DIC, presenting as weakened heart function. Besides, the levels of Malondialdehyde and Fe2+ in the cardiac tissue increased, along with diminished glutathione peroxidase 4 and Solute Carrier Family 7 Member 11 levels, and a decline in the concentration of glutathione, causing an increase in ferroptosis. Moreover, in vitro, we used dual-luciferase assay to confirm that Kelch Like ECH Associated Protein 1 (KEAP1) can be a target gene of mir-17-3p. We used Keap1/NFE2 Like BZIP Transcription Factor 2 (NRF2) inhibitor brusatol and Stimulator of Interferon Response CGAMP Interactor 1 (STING) agonist SR-717 to verify the mir-17-3p/KEAP1 axis can affect the Cyclic GMP-AMP Synthase (CGAS)/STING pathway, leading to further ferroptosis in DIC. This manifested as a reduction in ferroptosis. In summary, our research suggests swimming training enhances the levels of mir-17-3p, thereby activating the KEAP1/NRF2 pathway, and weakening the CGAS/STING pathway, improving ferroptosis in DIC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos