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Chang, C.-H., et al

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Inside the cell, cystine is reduced to cysteine and then cysteine is used by the enzymes c-glutamyl cysteine synthetase and glutathione synthetase for the synthesis of GSH ( - ) ( - is regulated by the nrf2-keap1 pathway (nrf2, nuclear factor E2-related factor-Kelch-like ECH-associated protein 1) ( - ) by increasing the level of glutamate or an exogenous stimulant, such as sulfasalazine, can deplete intracellular GSH, reduce Gpx4 substrate availability and disrupt the axis ( Figure 1 While inhibition of system Xc -mediated cystine uptake is sufficient for erastin-induced ferroptosis, it may not be necessary to execute ferroptosis given that RSL3-induced ferroptosis shares similar patterns with erastin-induced ferroptosis, which does not inhibit cystine uptake

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