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In contrast, at the pathological levels induced by OS, the highly electrophilic nature of 4-HNE can result in the formation of stable covalent Michael and Schiff base adducts to nucleophilic functional groups of proteins, such as the side chains of cysteine, lysine and histidine

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This pathway is independent of GPX4 and GSH and can still function when GPX4 is inactivated or GSH is depleted (25)

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