A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury
Summary: Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224007326 |
| _version_ | 1797242943221792768 |
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| author | Jiaojiao Yu Yu Zhang Qin Zhu Zhengrui Ren Mengting Wang Sasa Kong Hongbo Lv Tao Xu Zhaoyu Xie Han Meng Jun Han Hui Che |
| author_facet | Jiaojiao Yu Yu Zhang Qin Zhu Zhengrui Ren Mengting Wang Sasa Kong Hongbo Lv Tao Xu Zhaoyu Xie Han Meng Jun Han Hui Che |
| author_sort | Jiaojiao Yu |
| collection | DOAJ |
| description | Summary: Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons. |
| first_indexed | 2024-04-24T18:47:15Z |
| format | Article |
| id | doaj.art-3e1073d8a11c42c9bbc8859792b78f21 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T18:47:15Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3e1073d8a11c42c9bbc8859792b78f212024-03-27T04:52:44ZengElsevieriScience2589-00422024-04-01274109511A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injuryJiaojiao Yu0Yu Zhang1Qin Zhu2Zhengrui Ren3Mengting Wang4Sasa Kong5Hongbo Lv6Tao Xu7Zhaoyu Xie8Han Meng9Jun Han10Hui Che11Department of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, China; Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaSchool of Anesthesia, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, ChinaAnhui College of Traditional Chinese Medicine, Wuhu, China; Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, China; Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical College, Wuhu, China; Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical College, Wuhu, China; Corresponding authorDepartment of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, China; Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, China; Department of Endocrinology and Genetic Metabolism, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China; Corresponding authorSummary: Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.http://www.sciencedirect.com/science/article/pii/S2589004224007326Molecular biologyCell biology |
| spellingShingle | Jiaojiao Yu Yu Zhang Qin Zhu Zhengrui Ren Mengting Wang Sasa Kong Hongbo Lv Tao Xu Zhaoyu Xie Han Meng Jun Han Hui Che A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury iScience Molecular biology Cell biology |
| title | A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury |
| title_full | A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury |
| title_fullStr | A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury |
| title_full_unstemmed | A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury |
| title_short | A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury |
| title_sort | mechanism linking ferroptosis and ferritinophagy in melatonin related improvement of diabetic brain injury |
| topic | Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224007326 |
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