TY  - JOUR
A1  - Feger, Martina
A1  - Fajol, Abul
A1  - Lebedeva, Aleksandra
A1  - Meissner, Adrian
A1  - Michael, Diana
A1  - Völkl, Jakob
A1  - Alesutan, Ioana
A1  - Schleicher, Erwin
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
A1  - Qadri, Syed M.
A1  - Lang, Florian
T1  - Effect of Carbon Monoxide Donor CORM-2 on Vitamin D-3 Metabolism
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - 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 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.
KW  - CORM-2
KW  - 1,25-Dihydroxyvitamin D-3
KW  - Klotho
KW  - FGF23
KW  - Phosphate
KW  - Calcium
Y1  - 2013
U6  - https://doi.org/10.1159/000355730
SN  - 1420-4096
SN  - 1423-0143
VL  - 37
IS  - 4-5
SP  - 496
EP  - 505
PB  - Karger
CY  - Basel
ER  -