Martina Feger, Abul Fajol, Aleksandra Lebedeva, Adrian Meissner, Diana Michael, Jakob Völkl, Ioana Alesutan, Erwin Schleicher, Christoph Reichetzeder, Berthold Hocher, Syed M. Qadri, Florian Lang
- Background/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR andBackground/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 mu M CORM-2. Results: CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)(2)D-3 plasma levels, renal Cyp27b1 gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased Fgf23 transcript levels. Conclusion: CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)(2)D-3 synthesis.…
MetadatenVerfasserangaben: | Martina Feger, Abul Fajol, Aleksandra Lebedeva, Adrian Meissner, Diana Michael, Jakob Völkl, Ioana Alesutan, Erwin Schleicher, Christoph ReichetzederORCiDGND, Berthold HocherORCiDGND, Syed M. Qadri, Florian Lang |
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DOI: | https://doi.org/10.1159/000355730 |
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ISSN: | 1420-4096 |
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ISSN: | 1423-0143 |
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Titel des übergeordneten Werks (Englisch): | Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie |
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Verlag: | Karger |
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Verlagsort: | Basel |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Jahr der Erstveröffentlichung: | 2013 |
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Erscheinungsjahr: | 2013 |
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Datum der Freischaltung: | 26.03.2017 |
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Freies Schlagwort / Tag: | 1,25-Dihydroxyvitamin D-3; CORM-2; Calcium; FGF23; Klotho; Phosphate |
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Band: | 37 |
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Ausgabe: | 4-5 |
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Seitenanzahl: | 10 |
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Erste Seite: | 496 |
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Letzte Seite: | 505 |
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Fördernde Institution: | DFG; Open Access Publishing Fund of Tuebingen University |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access |
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