Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells
We examined the effect of immunosuppressant cyclosporin A (CsA) on the synthesis of tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide synthase (NOS), during treatment with lipopolysaccharide (LPS) in mouse brain microvascular endothelial cells. Addition of LPS to the endothelial cells...
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| Format: | Article |
| Language: | English |
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De Gruyter
2002-08-01
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| Series: | Pteridines |
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| Online Access: | https://doi.org/10.1515/pteridines.2002.13.3.89 |
| _version_ | 1818731863431184384 |
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| author | Ishii Masakazu Shimizu Shunichi Shiota Kazuhiro Yamamoto Shinichiro Kiuchi Yuji Yamamoto Toshinori |
| author_facet | Ishii Masakazu Shimizu Shunichi Shiota Kazuhiro Yamamoto Shinichiro Kiuchi Yuji Yamamoto Toshinori |
| author_sort | Ishii Masakazu |
| collection | DOAJ |
| description | We examined the effect of immunosuppressant cyclosporin A (CsA) on the synthesis of tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide synthase (NOS), during treatment with lipopolysaccharide (LPS) in mouse brain microvascular endothelial cells. Addition of LPS to the endothelial cells increased the BH4 content and the mRNA level of GTP-cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH4 synthesis, and the LPSínduced increases in both the BH4 content and expression of GTPCH mRNA were further stimulated by the cotreatment with CsA. 2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, blocked the increase in BH4 content induced by CsA during the LPS treatment. Moreover. CsA stimulated the expression of inducible NOS (iNOS) mRNA during the LPS treatment. These findings suggest that CsA stimulates LPS-induced BH4 synthesis through the induction of GTPCH, and iNOS expression. CsA may increase NO production during LPS treatment in brain microvascular endothelial cells. |
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| format | Article |
| id | doaj.art-835a0e296b534b7d80e46ba4c18497d7 |
| institution | Directory Open Access Journal |
| issn | 0933-4807 2195-4720 |
| language | English |
| last_indexed | 2024-12-17T23:24:26Z |
| publishDate | 2002-08-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Pteridines |
| spelling | doaj.art-835a0e296b534b7d80e46ba4c18497d72022-12-21T21:28:48ZengDe GruyterPteridines0933-48072195-47202002-08-01133899310.1515/pteridines.2002.13.3.89Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial CellsIshii Masakazu0Shimizu Shunichi1Shiota Kazuhiro2Yamamoto Shinichiro3Kiuchi Yuji4Yamamoto Toshinori5Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, JapanWe examined the effect of immunosuppressant cyclosporin A (CsA) on the synthesis of tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide synthase (NOS), during treatment with lipopolysaccharide (LPS) in mouse brain microvascular endothelial cells. Addition of LPS to the endothelial cells increased the BH4 content and the mRNA level of GTP-cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH4 synthesis, and the LPSínduced increases in both the BH4 content and expression of GTPCH mRNA were further stimulated by the cotreatment with CsA. 2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, blocked the increase in BH4 content induced by CsA during the LPS treatment. Moreover. CsA stimulated the expression of inducible NOS (iNOS) mRNA during the LPS treatment. These findings suggest that CsA stimulates LPS-induced BH4 synthesis through the induction of GTPCH, and iNOS expression. CsA may increase NO production during LPS treatment in brain microvascular endothelial cells.https://doi.org/10.1515/pteridines.2002.13.3.89cyclosporin atetrahydrobiopteringtp-cyclohydrolase ilipopolysaccharidemouse brain microvascular endothelial cells |
| spellingShingle | Ishii Masakazu Shimizu Shunichi Shiota Kazuhiro Yamamoto Shinichiro Kiuchi Yuji Yamamoto Toshinori Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells Pteridines cyclosporin a tetrahydrobiopterin gtp-cyclohydrolase i lipopolysaccharide mouse brain microvascular endothelial cells |
| title | Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells |
| title_full | Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells |
| title_fullStr | Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells |
| title_full_unstemmed | Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells |
| title_short | Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells |
| title_sort | stimulation of tetrahydrobiopterin synthesis by cyclosporin a during lipopolysaccharide treatment in vascular endothelial cells |
| topic | cyclosporin a tetrahydrobiopterin gtp-cyclohydrolase i lipopolysaccharide mouse brain microvascular endothelial cells |
| url | https://doi.org/10.1515/pteridines.2002.13.3.89 |
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