Inhibition of DNMT-1 alleviates ferroptosis through NCOA4 mediated ferritinophagy during diabetes myocardial ischemia/reperfusion injury
| Autor: | Li, Wenyuan, Li, Wei, Wang, Yao, Leng, Yan, Xia, Zhongyuan |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
QH573-671 business.industry Immunology Cell Ischemia Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell Biology Pharmacology medicine.disease GPX4 Article Blot Myocardial infarction Cellular and Molecular Neuroscience medicine.anatomical_structure Nuclear receptor Diabetes mellitus Coactivator Medicine Cytology business Ion channel signalling Reperfusion injury RC254-282 |
| Zdroj: | Cell Death Discovery Cell Death Discovery, Vol 7, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/s41420-021-00656-0 |
| Popis: | The purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2’-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated. |
| Databáze: | OpenAIRE |
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