Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway
Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12872-023-03603-2 |
| _version_ | 1797416192418250752 |
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| author | Yunfei Liao Ben Ke Xiaoyan Long Jianjun Xu Yongbing Wu |
| author_facet | Yunfei Liao Ben Ke Xiaoyan Long Jianjun Xu Yongbing Wu |
| author_sort | Yunfei Liao |
| collection | DOAJ |
| description | Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown to play critical roles in protecting cardiomyocytes against MIRI, but their specific protective mechanism, their interact between the two and their relationship with ferroptosis are still unclear. Hence, in this study, we investigated the interact and specific mechanism of SIRT1 and SIRT3 in protecting cardiomyocytes against MIRI, as well as their association with ferroptosis. Methods Bioinformatics analysis methods were used to explore the expression of SIRT1 and SIRT3 during MIRI, and then a cell hypoxia/reoxygenation injury model was constructed to verify the results. Then, Pearson correlation analysis was further used to explore the relationship between SIRT1 and SIRT3, whose roles in the regulation of ferroptosis were also analysed by gene knock down, Western Blotting and flow cytometry. Several biomarkers, such as Fe2+ concentration, lipid peroxidation marker MDA and mitochondrial membrane potential (MMP), were used to evaluate changes in ferroptosis. Results The expression of SIRT1 and SIRT3 was abnormal during MIRI, and SIRT1 was significantly negatively correlated with SIRT3 in the SIRT1-SIRT3 axis. Further analysis revealed that the SIRT1-SIRT3 axis was closely correlated with ferroptosis, and its silencing effectively increase the incidence of ferroptosis. Furthermore, SIRT1-SIRT3 axis silencing was accompanied by changes in PINK1, Parkin, P62/SQSTM1 and LC3 expression. PINK1 silencing significantly increased the incidence of ferroptosis, while resveratrol (Res) and/or honokiol (HKL) effectively reversed the outcome. Conclusion Abnormalities in the SIRT1-SIRT3 axis promote MIRI through ferroptosis caused by silencing the PINK1/Parkin signaling pathway. |
| first_indexed | 2024-03-09T05:59:55Z |
| format | Article |
| id | doaj.art-1b4b640f0d574718b167163cc6599526 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-03-09T05:59:55Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-1b4b640f0d574718b167163cc65995262023-12-03T12:09:50ZengBMCBMC Cardiovascular Disorders1471-22612023-11-0123111710.1186/s12872-023-03603-2Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathwayYunfei Liao0Ben Ke1Xiaoyan Long2Jianjun Xu3Yongbing Wu4Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Nephrology, The Second Affiliated Hospital of Nanchang UniversityEast China Digital Medical Engineering Research InstituteDepartment of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang UniversityAbstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown to play critical roles in protecting cardiomyocytes against MIRI, but their specific protective mechanism, their interact between the two and their relationship with ferroptosis are still unclear. Hence, in this study, we investigated the interact and specific mechanism of SIRT1 and SIRT3 in protecting cardiomyocytes against MIRI, as well as their association with ferroptosis. Methods Bioinformatics analysis methods were used to explore the expression of SIRT1 and SIRT3 during MIRI, and then a cell hypoxia/reoxygenation injury model was constructed to verify the results. Then, Pearson correlation analysis was further used to explore the relationship between SIRT1 and SIRT3, whose roles in the regulation of ferroptosis were also analysed by gene knock down, Western Blotting and flow cytometry. Several biomarkers, such as Fe2+ concentration, lipid peroxidation marker MDA and mitochondrial membrane potential (MMP), were used to evaluate changes in ferroptosis. Results The expression of SIRT1 and SIRT3 was abnormal during MIRI, and SIRT1 was significantly negatively correlated with SIRT3 in the SIRT1-SIRT3 axis. Further analysis revealed that the SIRT1-SIRT3 axis was closely correlated with ferroptosis, and its silencing effectively increase the incidence of ferroptosis. Furthermore, SIRT1-SIRT3 axis silencing was accompanied by changes in PINK1, Parkin, P62/SQSTM1 and LC3 expression. PINK1 silencing significantly increased the incidence of ferroptosis, while resveratrol (Res) and/or honokiol (HKL) effectively reversed the outcome. Conclusion Abnormalities in the SIRT1-SIRT3 axis promote MIRI through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.https://doi.org/10.1186/s12872-023-03603-2SIRT1-SIRT3 axisFerroptosisMitophagyPINK1/Parkin signaling pathwayMyocardial ischemia-reperfusion injury |
| spellingShingle | Yunfei Liao Ben Ke Xiaoyan Long Jianjun Xu Yongbing Wu Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway BMC Cardiovascular Disorders SIRT1-SIRT3 axis Ferroptosis Mitophagy PINK1/Parkin signaling pathway Myocardial ischemia-reperfusion injury |
| title | Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway |
| title_full | Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway |
| title_fullStr | Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway |
| title_full_unstemmed | Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway |
| title_short | Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway |
| title_sort | abnormalities in the sirt1 sirt3 axis promote myocardial ischemia reperfusion injury through ferroptosis caused by silencing the pink1 parkin signaling pathway |
| topic | SIRT1-SIRT3 axis Ferroptosis Mitophagy PINK1/Parkin signaling pathway Myocardial ischemia-reperfusion injury |
| url | https://doi.org/10.1186/s12872-023-03603-2 |
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