| Autor: |
Tian-Xiang Wang, Kun-Long Duan, Zi-Xuan Huang, Zi-An Xue, Jun-Yun Liang, Yongjun Dang, Ao Zhang, Yue Xiong, Chunyong Ding, Kun-Liang Guan, Hai-Xin Yuan |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Life science alliance. 6(1) |
| ISSN: |
2575-1077 |
| Popis: |
Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone fromSalvia miltiorrhiza(Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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