title: Effect of carbon monoxide donor CORM-2 on vitamin D3 metabolism.
abstract: OBJECTIVE
  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 D3 (1,25(OH)2D3) by renal 25-hydroxyvitamin D3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)2D3 regulates Ca(2+) and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)2D3 formation and klotho expression.
  
  
  METHODS
  Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)2D3 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 µM CORM-2.
  
  
  RESULTS
  CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)2D3 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.
  
  
  CONCLUSIONS
  CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)2D3 synthesis. © 2013 S. Karger AG, Basel.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Feger
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Lebedeva
authors.forename: Adrian
authors.initials: A
authors.lastname: Meissner
authors.forename: Diana
authors.initials: D
authors.lastname: Michael
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Erwin
authors.initials: E
authors.lastname: Schleicher
authors.forename: Christoph
authors.initials: C
authors.lastname: Reichetzeder
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage* / Q000097:blood; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000097:blood / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage*; D051381:Rats; D012428:Ruthenium
chemical_list: C000717428:Fgf23 protein, mouse; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D002762:Cholecalciferol; D000089703:Fibroblast Growth Factor-23; D002248:Carbon Monoxide; D012428:Ruthenium