What question did this study set out to answer?

To determine how electrophilic nitro-fatty acid regioisomers modify specific Keap1 cysteine residues to trigger Nrf2-mediated antioxidant gene expression.

February 26, 2011Journal of Biological ChemistryOpen Access

Electrophilic Nitro-fatty Acids Activate NRF2 by a KEAP1 Cysteine 151-independent Mechanism

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To determine how electrophilic nitro-fatty acid regioisomers modify specific Keap1 cysteine residues to trigger Nrf2-mediated antioxidant gene expression.
Examined the post-translational modification profile of Keap1 cysteines treated with 9- and 10-nitro-octadec-9-enoic acid (OA-NO2) in cellular systems.
Tested antioxidant response element (ARE) activation and Keap1-Cul3 protein interactions using wild-type and Cys151-mutated Keap1 constructs.
9-nitro-octadec-9-enoic acid served as a more potent ARE inducer than 10-nitro-octadec-9-enoic acid, with Cys273 and Cys288 together responsible for ~50% of total Keap1 nitroalkylation in cellular conditions.
Cys151 was among the least reactive residues, and mutating Cys151 did not affect overall Keap1 nitroalkylation or ARE induction.
OA-NO2 enhanced physical binding between Keap1 and Cul3 rather than disrupting the complex, identifying it as a non-canonical, Cys151-independent Nrf2 activator.

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Implication

Mechanistic study reveals nitro-fatty acids activate Nrf2 via non-Cys151 Keap1 modifications in cell models, indicating a distinct pathway for electrophile-mediated gene expression.

Cite This Study

Kansanen et al. (2011) studied this question.

synapsesocial.com/papers/6a778085d2fa2470761ee772 https://doi.org/10.1074/jbc.m110.190710

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Implication

Mechanistic study reveals nitro-fatty acids activate Nrf2 via non-Cys151 Keap1 modifications in cell models, indicating a distinct pathway for electrophile-mediated gene expression.

Electrophilic Nitro-fatty Acids Activate NRF2 by a KEAP1 Cysteine 151-independent Mechanism

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Discussion

Implication

Cite This Study

Electrophilic Nitro-fatty Acids Activate NRF2 by a KEAP1 Cysteine 151-independent Mechanism

Key Points

Discussion

Implication

Cite This Study

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