M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury
Objective Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.Methods We constructed the MIRI rat model and hypoxia/reoxygenation...
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Taylor & Francis Group
2025-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2025.2454892 |
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| author | Qiong Jiang Xuehai Chen Kezeng Gong Zhe Xu Lianglong Chen Feilong Zhang |
| author_facet | Qiong Jiang Xuehai Chen Kezeng Gong Zhe Xu Lianglong Chen Feilong Zhang |
| author_sort | Qiong Jiang |
| collection | DOAJ |
| description | Objective Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.Methods We constructed the MIRI rat model and hypoxia/reoxygenation (H/R) injury cardiomyocytes model. RT–PCR and Western blot were used to investigate the expression of the fat mass and obesity-associated (FTO) gene. Electrocardiogram, echocardiography, triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to assess the model and the effect of FTO overexpression. The generation of reactive oxygen species (ROS) and the levels of superoxide dismutase (SOD2), mitochondrial transcription factor (TFAM) and cytochrome c oxidase I (COXI) were detected to assess the oxidative stress and mitochondrial biogenesis. RNA immunoprecipitation (RIP) and RNA pulldown assays were used to identify the interaction of FTO and PGC-1a. The m6A dot blot, methylated RNA immunoprecipitation PCR (MeRIP-PCR) and RNA stability analysis were used to analyze the regulation of methylation of PGC-1a by FTO.Results FTO was downregulated in MIRI rats and H/R induced cardiomyocytes. Overexpression of FTO inhibited ROS level and increased the expression of SOD2, TFAM and COXI in vitro and in vivo. In addition, PGC-1a was identified as a downstream target of FTO. FTO enhanced the stability of PGC-1a mRNA through removing the m6A modification.Conclusion Our study revealed the role of FTO regulates the oxidative stress and mitochondrial biogenesis via PGC-1a in MIRI, which may provide a new approach to mitigating MIRI. |
| format | Article |
| id | doaj-art-3ad9fa72d3f24a75bd7093579360f76c |
| institution | Kabale University |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-3ad9fa72d3f24a75bd7093579360f76c2025-01-27T17:52:57ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2454892M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injuryQiong Jiang0Xuehai Chen1Kezeng Gong2Zhe Xu3Lianglong Chen4Feilong Zhang5Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaDepartment of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaDepartment of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaDepartment of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaDepartment of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaDepartment of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaObjective Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.Methods We constructed the MIRI rat model and hypoxia/reoxygenation (H/R) injury cardiomyocytes model. RT–PCR and Western blot were used to investigate the expression of the fat mass and obesity-associated (FTO) gene. Electrocardiogram, echocardiography, triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to assess the model and the effect of FTO overexpression. The generation of reactive oxygen species (ROS) and the levels of superoxide dismutase (SOD2), mitochondrial transcription factor (TFAM) and cytochrome c oxidase I (COXI) were detected to assess the oxidative stress and mitochondrial biogenesis. RNA immunoprecipitation (RIP) and RNA pulldown assays were used to identify the interaction of FTO and PGC-1a. The m6A dot blot, methylated RNA immunoprecipitation PCR (MeRIP-PCR) and RNA stability analysis were used to analyze the regulation of methylation of PGC-1a by FTO.Results FTO was downregulated in MIRI rats and H/R induced cardiomyocytes. Overexpression of FTO inhibited ROS level and increased the expression of SOD2, TFAM and COXI in vitro and in vivo. In addition, PGC-1a was identified as a downstream target of FTO. FTO enhanced the stability of PGC-1a mRNA through removing the m6A modification.Conclusion Our study revealed the role of FTO regulates the oxidative stress and mitochondrial biogenesis via PGC-1a in MIRI, which may provide a new approach to mitigating MIRI.https://www.tandfonline.com/doi/10.1080/13510002.2025.2454892FTOoxidative stressmitochondrial biogenesisPGC-1amyocardial ischemia-reperfusion injury |
| spellingShingle | Qiong Jiang Xuehai Chen Kezeng Gong Zhe Xu Lianglong Chen Feilong Zhang M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury Redox Report FTO oxidative stress mitochondrial biogenesis PGC-1a myocardial ischemia-reperfusion injury |
| title | M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury |
| title_full | M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury |
| title_fullStr | M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury |
| title_full_unstemmed | M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury |
| title_short | M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury |
| title_sort | m6a demethylase fto regulates the oxidative stress mitochondrial biogenesis of cardiomyocytes and pgc 1a stability in myocardial ischemia reperfusion injury |
| topic | FTO oxidative stress mitochondrial biogenesis PGC-1a myocardial ischemia-reperfusion injury |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2025.2454892 |
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