New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages
Dietary supplementation with L-arginine was shown to improve immune responses in various inflammatory models. However, the molecular mechanisms underlying L-arginine effects on immune cells remain unrecognized. Herein, we tested the hypothesis that a limitation of L-arginine could lead to the uncoup...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/2011/321979 |
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| author | Michaela Pekarova Antonin Lojek Hana Martiskova Ondrej Vasicek Lucia Bino A. Klinke D. Lau Radek Kuchta Jaroslav Kadlec Radimir Vrba Lukas Kubala |
| author_facet | Michaela Pekarova Antonin Lojek Hana Martiskova Ondrej Vasicek Lucia Bino A. Klinke D. Lau Radek Kuchta Jaroslav Kadlec Radimir Vrba Lukas Kubala |
| author_sort | Michaela Pekarova |
| collection | DOAJ |
| description | Dietary supplementation with L-arginine was shown to improve immune responses in various inflammatory models. However, the molecular mechanisms underlying L-arginine effects on immune cells remain unrecognized. Herein, we tested the hypothesis that a limitation of L-arginine could lead to the uncoupled state of murine macrophage inducible nitric oxide synthase and, therefore, increase inducible nitric-oxide-synthase-derived superoxide anion formation. Importantly, we demonstrated that L-arginine dose- and time dependently potentiated superoxide anion production in bacterial endotoxin-stimulated macrophages, although it did not influence NADPH oxidase expression and activity. Detailed analysis of macrophage activation showed the time dependence between LPS-induced iNOS expression and increased O2∙- formation. Moreover, downregulation of macrophage iNOS expression, as well as the inhibition of iNOS activity by NOS inhibitors, unveiled an important role of this enzyme in controlling O2∙- and peroxynitrite formation during macrophage stimulation. In conclusion, our data demonstrated that simultaneous induction of NADPH oxidase, together with the iNOS enzyme, can result in the uncoupled state of iNOS resulting in the production of functionally important levels of O2∙- soon after macrophage activation with LPS. Moreover, we demonstrated, for the first time that increased concentrations of L-arginine further potentiate iNOS-dependent O2∙- formation in inflammatory macrophages. |
| format | Article |
| id | doaj-art-f888049bde0d46e49ada73681f66cd22 |
| institution | OA Journals |
| issn | 1537-744X |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-f888049bde0d46e49ada73681f66cd222025-08-20T02:22:34ZengWileyThe Scientific World Journal1537-744X2011-01-01112443245710.1100/2011/321979321979New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 MacrophagesMichaela Pekarova0Antonin Lojek1Hana Martiskova2Ondrej Vasicek3Lucia Bino4A. Klinke5D. Lau6Radek Kuchta7Jaroslav Kadlec8Radimir Vrba9Lukas Kubala10Institute of Biophysics, The Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics, The Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics, The Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics, The Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics, The Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech RepublicDepartment of Cardiology, Hamburg University Heart Center, Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Cardiology, Hamburg University Heart Center, Martinistrasse 52, 20246 Hamburg, GermanyFaculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3058/10, 616 00 Brno, Czech RepublicFaculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3058/10, 616 00 Brno, Czech RepublicFaculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3058/10, 616 00 Brno, Czech RepublicInstitute of Biophysics, The Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech RepublicDietary supplementation with L-arginine was shown to improve immune responses in various inflammatory models. However, the molecular mechanisms underlying L-arginine effects on immune cells remain unrecognized. Herein, we tested the hypothesis that a limitation of L-arginine could lead to the uncoupled state of murine macrophage inducible nitric oxide synthase and, therefore, increase inducible nitric-oxide-synthase-derived superoxide anion formation. Importantly, we demonstrated that L-arginine dose- and time dependently potentiated superoxide anion production in bacterial endotoxin-stimulated macrophages, although it did not influence NADPH oxidase expression and activity. Detailed analysis of macrophage activation showed the time dependence between LPS-induced iNOS expression and increased O2∙- formation. Moreover, downregulation of macrophage iNOS expression, as well as the inhibition of iNOS activity by NOS inhibitors, unveiled an important role of this enzyme in controlling O2∙- and peroxynitrite formation during macrophage stimulation. In conclusion, our data demonstrated that simultaneous induction of NADPH oxidase, together with the iNOS enzyme, can result in the uncoupled state of iNOS resulting in the production of functionally important levels of O2∙- soon after macrophage activation with LPS. Moreover, we demonstrated, for the first time that increased concentrations of L-arginine further potentiate iNOS-dependent O2∙- formation in inflammatory macrophages.http://dx.doi.org/10.1100/2011/321979 |
| spellingShingle | Michaela Pekarova Antonin Lojek Hana Martiskova Ondrej Vasicek Lucia Bino A. Klinke D. Lau Radek Kuchta Jaroslav Kadlec Radimir Vrba Lukas Kubala New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages The Scientific World Journal |
| title | New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages |
| title_full | New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages |
| title_fullStr | New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages |
| title_full_unstemmed | New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages |
| title_short | New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages |
| title_sort | new role for l arginine in regulation of inducible nitric oxide synthase derived superoxide anion production in raw 264 7 macrophages |
| url | http://dx.doi.org/10.1100/2011/321979 |
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