Cystine/glutamate transporter, system x, is involved in nitric oxide production in mouse peritoneal macrophages.

The amino acid transport system x is important for maintaining intracellular glutathione levels and extracellular redox balance. The main component of system x, xCT, is strongly induced by various stimuli, including oxidative stress and bacterial lipopolysaccharides (LPS) in macrophages. In the present study, we investigated the production of nitric oxide by LPS-stimulated mouse peritoneal macrophages isolated from both xCT-deficient and wild-type mice.

The ferroptosis inducer erastin irreversibly inhibits system x- and synergizes with cisplatin to increase cisplatin's cytotoxicity in cancer cells.

System x was recently described as the most upstream node in a novel form of regulated necrotic cell death, called ferroptosis. In this context, the small molecule erastin was reported to target and inhibit system x, leading to cysteine starvation, glutathione depletion and consequently ferroptotic cell death. Although the inhibitory effect of erastin towards system x is well-documented, nothing is known about its mechanism of action.

Decreased reproductive performance in xCT-knockout male mice.

Sulphoxidation occurs in protamines that are enriched in cysteine and supplies chromatin for packaging. The extracellular fluid contains higher levels of oxidised cysteine (cystine), and some cells utilise system x, a cystine transporter in which xCT is the main protein component, to fulfil the need for cysteine. We hypothesised that system x might ensure the supply of cysteine needed for spermatogenesis.