Sustained Nitric Oxide Production in Macrophages Requires the Arginine Transporter CAT2
| Autor: | Carol L. MacLeod, Jeanine Kleeman, Benjamin Nicholson, Cathyryne K. Manner |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Lipopolysaccharides
Transcription Genetic Arginine Molecular Sequence Data Nitric Oxide Synthase Type II Nitric Oxide Biochemistry Nitric oxide Mice chemistry.chemical_compound Tumor Cells Cultured Extracellular Animals Amino Acid Sequence Amino acid transporter Molecular Biology Mice Knockout Arginine transport Base Sequence ATP synthase biology Macrophages Mammary Neoplasms Experimental Membrane Proteins Transporter Cell Biology Gene Expression Regulation chemistry biology.protein Amino Acid Transport Systems Basic Cytokines Female Nitric Oxide Synthase Carrier Proteins Intracellular |
| Zdroj: | Journal of Biological Chemistry. 276:15881-15885 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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