H3K9 trimethylation dictates neuronal ferroptosis through repressing Tfr1
| العنوان: | H3K9 trimethylation dictates neuronal ferroptosis through repressing Tfr1 |
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| المؤلفون: | Ting Lan, Liye Hu, Tingting Sun, Xuechun Wang, Zhongnan Xiao, Danmin Shen, Weihua Wu, Zhaoli Luo, Chao Wei, Xiaotong Wang, Meng Liu, Yi Guo, Liyong Wang, Yamei Wang, Yabin Lu, Yan Yu, Fei Yang, Chenguang Zhang, Qian Li |
| المصدر: | Journal of Cerebral Blood Flow & Metabolism. :0271678X2311656 |
| بيانات النشر: | SAGE Publications, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Neurology, Neurology (clinical), Cardiology and Cardiovascular Medicine |
| الوصف: | Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high morbidity and mortality worldwide. We have previously shown that ferroptosis contributes to neuronal loss in ICH mice. The overload of iron and dysfunction of glutathione peroxidase 4 (GPx4) promote neuronal ferroptosis post-ICH. However, how epigenetic regulatory mechanisms affect the ferroptotic neurons in ICH remains unclear. In the current study, hemin was used to induce ferroptosis in N2A and SK-N-SH neuronal cells to mimic ICH. The results showed that hemin-induced ferroptosis was accompanied by an increment of global level of trimethylation in histone 3 lysine 9 (H3K9me3) and its methyltransferase Suv39h1. Transcriptional target analyses indicated that H3K9me3 was enriched at the promoter region and gene body of transferrin receptor gene 1 ( Tfr1) and repressed its expression upon hemin stimulation. Inhibition of H3K9me3 with inhibitor or siRNA against Suv39h1 aggravated hemin- and RSL3-induced ferroptosis by upregulating Tfr1 expression. Furthermore, Suv39h1-H3K9me3 mediated repression of Tfr1 contributes to the progression of ICH in mice. These data suggest a protective role of H3K9me3 in ferroptosis post ICH. The knowledge gained from this study will improve the understanding of epigenetic regulation in neuronal ferroptosis and shed light on future clinical research after ICH. |
| تدمد: | 1559-7016 0271-678X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::58ed51c8e6a916cac3c3819560251840Test https://doi.org/10.1177/0271678x231165653Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........58ed51c8e6a916cac3c3819560251840 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15597016 0271678X |
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