Academic Journal
Med1 inhibits ferroptosis and alleviates liver injury in acute liver failure via Nrf2 activation
| العنوان: | Med1 inhibits ferroptosis and alleviates liver injury in acute liver failure via Nrf2 activation |
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| المؤلفون: | Lei, Zi-Ying, Li, Zhi-Hui, Lin, Deng-Na, Cao, Jing, Chen, Jun-Feng, Meng, Shi-Bo, Wang, Jia-Lei, Liu, Jing, Zhang, Jing, Lin, Bing-Liang |
| المساهمون: | National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Guangzhou Municipal Science and Technology Program key projects, National Major Science and Technology Projects of China, Basic and Applied Basic Research Foundation of Guangdong Province |
| المصدر: | Cell & Bioscience ; volume 14, issue 1 ; ISSN 2045-3701 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| الوصف: | Background Extensive hepatocyte mortality and the absence of specific medical therapy significantly contribute to the unfavorable prognosis of acute liver failure (ALF). Ferroptosis is a crucial form of cell death involved in ALF. In this study, we aimed to determine the impact of Mediator complex subunit 1 (Med1) on ferroptosis and its potential hepatoprotective effects in ALF. Results Med1 expression is diminished in the liver of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice, as well as in hepatocytes damaged by H 2 O 2 or TNF-α/D-GalN in vitro. Med1 overexpression mitigates liver injury and decreases the mortality rate of ALF mice by ferroptosis inhibition. The mechanism by which Med1 inhibits erastin-induced ferroptosis in hepatocytes involves the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, Med1 overexpression suppresses the transcription of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver of mice with LPS/D-GalN-induced ALF. Conclusion Overall, our research findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2. These findings substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF. Graphical Abstract |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s13578-024-01234-4 |
| DOI: | 10.1186/s13578-024-01234-4.pdf |
| DOI: | 10.1186/s13578-024-01234-4/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s13578-024-01234-4 https://link.springer.com/content/pdf/10.1186/s13578-024-01234-4.pdf https://link.springer.com/article/10.1186/s13578-024-01234-4/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.6916CE80 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13578-024-01234-4 |
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