Enhanced vulnerability to oxidative stress under Serine deprivation

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Here, we show that l-Ser depletion raises intracellular H2O2 levels and enhances vulnerability to oxidative stress in Phgdh-deficient mouse embryonic fibroblasts. These changes were associated with reduced total glutathione levels. Moreover, levels of the inflammatory markers thioredoxin-interacting protein and prostaglandin-endoperoxide synthase 2 were upregulated under l-Ser-depleted conditions; this was suppressed by the addition of N-acetyl-l-cysteine. Thus, intracellular l-Ser deficiency triggers an inflammatory response via increased oxidative stress, and de novo l-Ser synthesis suppresses oxidative stress damage and inflammation when the external l-Ser supply is restricted.

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