| Autor: |
Xiao-Hui Ma, Jiang-Han-Zi Liu, Chun-Yu Liu, Wan-Yang Sun, Wen-Jun Duan, Guan Wang, Hiroshi Kurihara, Rong-Rong He, Yi-Fang Li, Yang Chen, Hongcai Shang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2059-3635 |
| DOI: |
10.1038/s41392-022-01090-z |
| Popis: |
Abstract Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a “burning point” to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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