期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2022
卷号：71
期号：1
页码：48-54
DOI：10.3164/jcbn.21-143
语种：English
出版社：The Society for Free Radical Research Japan
摘要：Glutathione (GSH) is synthesized from three amino acids and the overall process is highly dependent on the availability of
l-cysteine (
l-Cys). GSH serves as an essential cofactor for glutathione peroxidase 4 (Gpx4), which reduces phospholipid hydroperoxides. The inactivation of Gpx4 or an insufficient supply of
l-Cys results in the accumulation of lipid hydroperoxides, eventually leading to iron-dependent cell death, ferroptosis. In this study, we investigated the anti-ferroptotic properties of
d-cysteine (
d-Cys) under conditions of dysfunction in cystine transporter, xCT.
l-Cys supplementation completely rescued ferroptosis that had been induced by the erastin-mediated inhibition of xCT in Hepa 1-6 cells. Upon
d-Cys supplementation, the erastin-treated cells remained completely viable for periods of up to 24 h but eventually died after 48 h.
d-Cys supplementation suppressed the production of lipid peroxides, thereby ferroptosis. The addition of
d-Cys sustained intracellular Cys and GSH levels to a certain extent. When Hepa 1-6 cells were treated with a combination of buthionine sulfoximine and erastin, the anti-ferroptotic effect of
d-Cys was diminished. These collective results indicate that, although
d-Cys is not the direct source of GSH,
d-Cys supplementation protects cells from ferroptosis in a manner that is dependent on GSH synthesis via stimulating the uptake of
l-Cys.
