Towards a modern definition of vitamin E—evidence for a quinone hypothesis

Shrader, William D.; Amagata, Akiko; Barnes, Adam; Hinman, A. Scott; Jankowski, Orion D.; Lee, Edgar; Kheifets, Viktoria; Komatsuzaki, Ryo; Mollard, Paul; Murase, Katsuyuki; Rioux, Patrice; Wesson, Kieron E.; Miller, Guy

doi:10.1016/j.bmcl.2011.10.117

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…Previously, we reported that quinone metabolites of vitamin E have potent rescue activity in a glutathione (GSH) depletion cell survival assay which exhibited features of ferroptotic cell death [ 10 – 14 ]. To test the hypothesis that the quinone and/or hydroquinone metabolites of alpha-tocopherol ( αT ) are responsible for its previously reported anti-ferroptotic activity [ 6 , 15 – 19 ], we evaluated the activity of alpha-tocopherol quinone ( αTQ ) and hydroquinone ( αTHQ ) in a ferroptotic cell death assay using immortalized mouse striatal cells (ST Hdh Q7/Q7 , hereafter referred to as Q7) [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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“…In the central nervous system, the up-regulation of NQO1 and HO-1 expressions could protect neurons against oxidative stress as well as a wide range of other endogenous toxins (Yuan et al, 2010). NQO1 was participated in anti-oxidation mediated by vitamin E, maintained redox state of intracellular vitamin E, and thus played an antioxidant effect (Shrader et al, 2012). The results of animal experiments were found that the incidence of cerebral hemorrhage and the severity of neuronal damage in NQO1 knockout mice were significantly higher than that of wild-type mice (Xu et al, 2014;Cheng et al, 2013).…”

Section: Discussionmentioning

confidence: 97%

Effects of N-butylphthalide on the activation of Keap1/Nrf-2 signal pathway in rats after carbon monoxide poisoning

Cheng

et al. 2015

Environmental Toxicology and Pharmacology

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“…It is likely that exposing the plant to a high light stress or any other treatment resulting in an increased oxidation of α-TC might lead to stronger changes in α-TQ levels. The formation of α-TQ, in fact, is relevant as a response to photooxidative and low-temperature stress where oxidation of α-TC forms α-tocopheroxyl radical which decomposes to a more stable α-TQ but is also dependent on α-TC availability [ 44 ] Arabidopsis vte4 mutants which accumulate γ-TC instead of α-TC in their leaves do not show any trace of α-TQ [ 45 ]. In our experiments, however, we did not detect a significant increase in α-TQ in leaves overexpressing VTE4 and p-crtB , meaning that, in control conditions, the direct conversion of α-TC (highly present in VTE4 -overexpressing leaves) to α-TQ, is limited.…”

Section: Resultsmentioning

confidence: 99%

Nutritional Enrichment of Plant Leaves by Combining Genes Promoting Tocopherol Biosynthesis and Storage

et al. 2023

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The enrichment of plant tissues in tocochromanols (tocopherols and tocotrienols) is an important biotechnological goal due to their vitamin E and antioxidant properties. Improvements based on stimulating tocochromanol biosynthesis have repeatedly been achieved, however, enhancing sequestering and storage in plant plastids remains virtually unexplored. We previously showed that leaf chloroplasts can be converted into artificial chromoplasts with a proliferation of plastoglobules by overexpression of the bacterial crtB gene. Here we combined coexpression of crtB with genes involved in tocopherol biosynthesis to investigate the potential of artificial leaf chromoplasts for vitamin E accumulation in Nicotiana benthamiana leaves. We show that this combination improves tocopherol levels compared to controls without crtB and confirm that VTE1, VTE5, VTE6 and tyrA genes are useful to increase the total tocopherol levels, while VTE4 further leads to enrichment in α-tocopherol (the tocochromanol showing highest vitamin E activity). Additionally, we show that treatments that further promote plastoglobule formation (e.g., exposure to intense light or dark-induced senescence) result in even higher improvements in the tocopherol content of the leaves. An added advantage of our strategy is that it also results in increased levels of other related plastidial isoprenoids such as carotenoids (provitamin A) and phylloquinones (vitamin K1).

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Towards a modern definition of vitamin E—evidence for a quinone hypothesis

Cited by 11 publications

References 36 publications

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

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

Effects of N-butylphthalide on the activation of Keap1/Nrf-2 signal pathway in rats after carbon monoxide poisoning

Nutritional Enrichment of Plant Leaves by Combining Genes Promoting Tocopherol Biosynthesis and Storage

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