Angeli, Jose Pedro Friedmann and Schneider, Manuela and Proneth, Bettina and Tyurina, Yulia Y. and Tyurin, Vladimir A. and Hammond, Victoria J. and Herbach, Nadja and Aichler, Michaela and Walch, Axel and Eggenhofer, Elke and Basavarajappa, Devaraj and Radmark, Olof and Kobayashi, Sho and Seibt, Tobias and Beck, Heike and Neff, Frauke and Esposito, Irene and Wanke, Ruediger and Foerster, Heidi and Yefremova, Olena and Heinrichmeyer, Marc and Bornkamm, Georg W. and Geissler, Edward K. and Thomas, Stephen B. and Stockwell, Brent R. and O'Donnell, Valerie B. and Kagan, Valerian E. and Schick, Joel A. and Conrad, Marcus (2014) Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. NATURE CELL BIOLOGY, 16 (12). 1180-U120. ISSN 1465-7392, 1476-4679
Full text not available from this repository. (Request a copy)Abstract
Ferroptosis is a non-apoptotic form of cell death induced by small molecules in specific tumour types, and in engineered cells overexpressing oncogenic RAS. Yet, its relevance in non-transformed cells and tissues is unexplored and remains enigmatic. Here, we provide direct genetic evidence that the knockout of glutathione peroxidase 4 (Gpx4) causes cell death in a pathologically relevant form of ferroptosis. Using inducible Gpx4(-/-) mice, we elucidate an essential role for the glutathione/Gpx4 axis in preventing lipid-oxidation-induced acute renal failure and associated death. We furthermore systematically evaluated a library of small molecules for possible ferroptosis inhibitors, leading to the discovery of a potent spiroquinoxalinamine derivative called Liproxstatin-1, which is able to suppress ferroptosis in cells, in Gpx4(-/-) mice, and in a pre-clinical model of ischaemia/reperfusion-induced hepatic damage. In sum, we demonstrate that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL-DEATH; OXIDATIVE STRESS; CYTOCHROME-C; GLUTATHIONE; IRON; 5-LIPOXYGENASE; PHOSPHOLIPIDS; INFLAMMATION; CARDIOLIPIN; DISRUPTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Aug 2019 09:08 |
| Last Modified: | 07 Aug 2019 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9140 |
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