title: Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages.
abstract: Amino acid transport in mouse peritoneal macrophages is mediated by several membrane carriers with different substrate specificity and sensitivity to environmental stimuli. We reported previously that transport activities of cystine and arginine in the macrophages were induced markedly by low concentrations of bacterial lipopolysaccharide (LPS). It is known that a variety of macrophage functions are affected by ambient oxygen tension. In this study, we have investigated the effects of oxygen on the induction of amino acid transport activity by LPS and found that the induction of cystine, but not arginine, transport activity was dependent on the ambient oxygen tension. When the macrophages were cultured with 2% O(2) in the presence of 1 ng/ml LPS, induction of cystine transport activity was reduced by approximately 70% compared with cells cultured under normoxic conditions. In macrophages, transport of cystine is mediated by a Na(+)-independent anionic amino acid transporter named system x(c)(-). System x(c)(-) is composed of two protein components, xCT and 4F2hc, and the expression of xCT was closely correlated with system x(c)(-) activity. A putative NF-kappaB binding site was found in the 5'-flanking region of the xCT gene, but the enhanced expression of xCT by LPS and oxygen was not mediated by NF-kappaB binding. An increase in intracellular GSH in macrophages paralleled induction of xCT, but not gamma-glutamylcysteine synthetase. These results suggest the importance of system x(c)(-) in antioxidant defense in macrophages exposed to LPS and oxidative stress.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575 Japan. hideyo-s@md.tsukuba.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Kuriyama-Matsumura
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: G E
authors.initials: GE
authors.lastname: Mann
authors.forename: S
authors.initials: S
authors.lastname: Bannai
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000975:Antioxidants; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D003553:Cystine / Q000378:metabolism* / Q000493:pharmacokinetics; D004151:Dipeptides / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D004151:Dipeptides; D008070:Lipopolysaccharides; D008298:Maleates; D016328:NF-kappa B; D012333:RNA, Messenger; D003553:Cystine; D005721:Glutamate-Cysteine Ligase; C014476:diethyl maleate; D005978:Glutathione; C017341:gamma-glutamylcysteine; D010100:Oxygen