Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase.

Autor: Hinman A; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Holst CR; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Latham JC; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Bruegger JJ; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Ulas G; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., McCusker KP; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Amagata A; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Davis D; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Hoff KG; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Kahn-Kirby AH; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Kim V; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Kosaka Y; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Lee E; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Malone SA; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Mei JJ; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Richards SJ; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Rivera V; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Miller G; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Trimmer JK; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America., Shrader WD; BioElectron Technology Corporation, Inc., Mountain View, California, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Aug 15; Vol. 13 (8), pp. e0201369. Date of Electronic Publication: 2018 Aug 15 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0201369
Abstrakt: Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.
Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors are employees of, and/or hold equity in BioElectron Technology Corporation, Inc. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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