| First Author | Nicholson B | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 19 | Pages | 15881-5 |
| PubMed ID | 11278602 | Mgi Jnum | J:69414 |
| Mgi Id | MGI:1934545 | Doi | 10.1074/jbc.M010030200 |
| Citation | Nicholson B, et al. (2001) Sustained nitric oxide production in macrophages requires the arginine transporter CAT2. J Biol Chem 276(19):15881-5 |
| abstractText | The aberrant production of nitric oxide (NO) contributes to the pathogenesis of diseases as diverse as cancer and arthritis. Sustained NO production via the inducible enzyme, nitric-oxide synthase 2 (NOS2), requires extracellular arginine uptake. Three closely related cationic amino acid transporter genes (Cat1-3) encode the transporters that mediate most arginine uptake in mammalian cells. Because CAT2 is induced coordinately with NOS2 in numerous cell types, we investigated a possible role for CAT2-mediated arginine transport in regulating NO production. The complexity of arginine transport systems and their biochemically similar transport properties called for a genetic approach to determine the role of CAT2. CAT2-deficient mice were generated and found to be healthy and fertile in contrast to Cat1(-/-) animals. Analysis of cytokine-activated macrophages from Cat2(-/-) mice revealed a 92% reduction in NO production and a 95% reduction in l-Arg uptake. The reduction in NO production was not due to differences in NOS2 protein expression, NOS2 activity, or intracellular l-arginine content. In conclusion, our results show that sustained abundant NO synthesis by macrophages requires arginine transport via the CAT2 transporter. |
