Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1
Summary: Obstructive sleep apnea (OSA) is a common sleep disordered breathing diseases that characterized by chronic intermittent hypoxia (CIH). This work aimed to explore the role of circ-CIMIRC in CIH-induced myocardial injury. CIH aggravated myocardial tissue damage in rats. Circ_CIMIRC overexpre...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224002037 |
| _version_ | 1797328631218831360 |
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| author | Runhua Wu Fengsheng Xu Jingyi Li Feng Wang Naijie Chen Xiaoting Wang Qin Chen |
| author_facet | Runhua Wu Fengsheng Xu Jingyi Li Feng Wang Naijie Chen Xiaoting Wang Qin Chen |
| author_sort | Runhua Wu |
| collection | DOAJ |
| description | Summary: Obstructive sleep apnea (OSA) is a common sleep disordered breathing diseases that characterized by chronic intermittent hypoxia (CIH). This work aimed to explore the role of circ-CIMIRC in CIH-induced myocardial injury. CIH aggravated myocardial tissue damage in rats. Circ_CIMIRC overexpression promoted apoptosis and reduced the colocalization of Tom20 and Parkin and mitophagy in CIH-treated H9c2 cells. Additionally, FbxL4 interacted with PINK1, FbxL4 silencing reduced PINK1 ubiquitination in H9c2 cells. Two major ubiquitination sites (K319 and K433) were responsible for ubiquitination of PINK1. Circ_CIMIRC promoted FbxL4-mediated ubiquitination and degradation of PINK1. Furthermore, circ_CIMIRC inhibition alleviated the pathological damage, fibrosis and apoptosis of myocardial tissues, reduced oxidative stress in CIH rats. In conclusion, circ_CIMIRC silencing repressed FbxL4-mediated ubiquitination and degradation of PINK1 and then enhanced PINK1/Parkin-mediated mitophagy, thereby alleviating myocardial damage in CIH rats. Thus, circ_CIMIRC may be a potential strategy to alleviate CIH-induced myocardial damage. |
| first_indexed | 2024-03-08T06:54:29Z |
| format | Article |
| id | doaj.art-ec3ee9e04a1849b0954802f17ec2d997 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T06:54:29Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ec3ee9e04a1849b0954802f17ec2d9972024-02-03T06:39:08ZengElsevieriScience2589-00422024-02-01272108982Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1Runhua Wu0Fengsheng Xu1Jingyi Li2Feng Wang3Naijie Chen4Xiaoting Wang5Qin Chen6College of Integrated Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Integrated Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Integrated Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Integrated Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Integrated Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaClinical Skills Teaching Center, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaClinical Skills Teaching Center, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, China; Corresponding authorSummary: Obstructive sleep apnea (OSA) is a common sleep disordered breathing diseases that characterized by chronic intermittent hypoxia (CIH). This work aimed to explore the role of circ-CIMIRC in CIH-induced myocardial injury. CIH aggravated myocardial tissue damage in rats. Circ_CIMIRC overexpression promoted apoptosis and reduced the colocalization of Tom20 and Parkin and mitophagy in CIH-treated H9c2 cells. Additionally, FbxL4 interacted with PINK1, FbxL4 silencing reduced PINK1 ubiquitination in H9c2 cells. Two major ubiquitination sites (K319 and K433) were responsible for ubiquitination of PINK1. Circ_CIMIRC promoted FbxL4-mediated ubiquitination and degradation of PINK1. Furthermore, circ_CIMIRC inhibition alleviated the pathological damage, fibrosis and apoptosis of myocardial tissues, reduced oxidative stress in CIH rats. In conclusion, circ_CIMIRC silencing repressed FbxL4-mediated ubiquitination and degradation of PINK1 and then enhanced PINK1/Parkin-mediated mitophagy, thereby alleviating myocardial damage in CIH rats. Thus, circ_CIMIRC may be a potential strategy to alleviate CIH-induced myocardial damage.http://www.sciencedirect.com/science/article/pii/S2589004224002037Molecular biologyCell biology |
| spellingShingle | Runhua Wu Fengsheng Xu Jingyi Li Feng Wang Naijie Chen Xiaoting Wang Qin Chen Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1 iScience Molecular biology Cell biology |
| title | Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1 |
| title_full | Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1 |
| title_fullStr | Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1 |
| title_full_unstemmed | Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1 |
| title_short | Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1 |
| title_sort | circ cimirc inhibition alleviates cih induced myocardial damage via fbxl4 mediated ubiquitination of pink1 |
| topic | Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224002037 |
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