Cystine/glutamate transporter, system xc−, is involved in nitric oxide production in mouse peritoneal macrophages

Publication date: 1 August 2018Source: Nitric Oxide, Volume 78Author(s): Sho Kobayashi, Shinji Hamashima, Takujiro Homma, Mami Sato, Ryosuke Kusumi, Shiro Bannai, Junichi Fujii, Hideyo SatoAbstractThe amino acid transport system xc− is important for maintaining intracellular glutathione levels and extracellular redox balance. The main component of system xc−, 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. After culturing macrophages in the presence of LPS for 24–48 h, nitrite levels in the medium of xCT-deficient macrophages were significantly decreased compared to that of wild-type cells. However, the transport activity of arginine, a precursor of nitric oxide, and the expression of nitric oxide synthase 2 in xCT-deficient macrophages were similar to those of wild-type cells. When wild-type macrophages were cultured in the medium that contained no cystine, nitric oxide production was decreased to the level similar to that of the xCT-deficient macrophages. When xCT-deficient macrophages were cultured with 2-mercaptoethanol, intracellular cysteine levels were increased and nitrite accumulation in the medium was significantly increased. On the other hand, when these cells were cultured with buthionine sulfoximine, an inhibit...

Source: Nitric Oxide - July 11, 2018 Category: Chemistry Source Type: research