4-Hydroxy-2-Nonenal Promotes Cardiomyocyte Necroptosis via Stabilizing Receptor-Interacting Serine/Threonine-Protein Kinase 1

• DOI: 10.3389/fcell.2021.721795
• Publication Date: 2021-10-01T14:32:34Z
• Authors: Xiaoxuan Zhai; Wenjun Wang; Shukun Sun; Yu Han; Jiaxin Li; Shengchuan Cao; Ruochuan Li; Tonghui Xu; Qiuhuan Yuan; Jiali Wang; Shujian Wei; Yuguo Chen
• Keywords: Cytoprotection

Background: Necroptosis is a vital regulator of myocardial ischemia/reperfusion (MI/R) injury. Meanwhile, 4-hydroxy-2-nonenal (4-HNE) abundantly increased during MI/R However, whether 4-HNE induces cardiomyocyte necroptosis remains unknown. Methods: To observe the relationship between and MI/R, C57BL/6 mice aldehyde dehydrogenase 2-transgenic (ALDH2-Tg) were both exposed to left anterior descending artery ligation surgery establish injury models. For further study, isolated mouse hearts H9c2 cells treated with elucidate underlying mechanisms. Results: upregulated in I/R-injured hearts. Cardiomyocyte was significantly decreased from ALDH2-Tg as compared that wild-type mice. In vitro studies showed enhanced by perfusion time- concentration-dependent manner. Knockdown receptor-interacting serine/threonine-protein kinase 1 (RIP1) using small interfering RNA (siRNA) prevented 4-HNE-induced necroptosis, manifesting RIP1 played key role upregulation cell 4-HNE. Further found reduced protein degradation preventing K48-polyubiquitination RIP1. Conclusion: contributes regulating ubiquitin-mediated proteasome