Iron ions derived from the nitric oxide donor sodium nitroprusside inhibit mineralization.
Sodium nitroprusside (SNP) is a nitric oxide (NO) donor drug, which is therapeutically used as a vasodilating drug in heart transplantations. In our previous study it was found that SNP at a concentration of 100 microM inhibited mineralization in a cell culture system, indicating that the beneficial effects of this drug may also include inhibition of vascular calcification. The aim of this study was to investigate which bioactive compounds generated from SNP inhibit mineralization. ATDC5 cells were grown for 14 days and mineralization was induced by addition of 5 mM phosphate for 24 h. Mineralization was determined by staining precipitated calcium with an alizarin red stain. It was found that the NO donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine were not able to inhibit mineralization and NO scavengers could not antagonize the inhibiting effect of SNP on mineralization. The iron chelator deferoxamine (200 microM) antagonized the inhibiting effect on mineralization mediated by SNP and ammonium iron sulfate inhibited mineralization in a dose-dependent manner (10-100 microM). Furthermore, iron ions (30 microM) were detected to be released from SNP in the cell culture. These data show that the iron moiety of sodium nitroprusside, rather than nitric oxide inhibits mineralization.
Huitema
Leonie F A
LF
Department of Biochemistry and Cell Biology, Utrecht University, P.O. Box 80.176, NL-3508 TD Utrecht, The Netherlands. L.F.A.Huitema@vet.uu.nl
van Weeren
P René
PR
Barneveld
Ab
A
van de Lest
Chris H A
CH
Helms
J Bernd
JB
Vaandrager
Arie B
AB
D000818:Animals; D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D005292:Ferricyanides / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007501:Iron / Q000737:chemistry / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D008903:Minerals / Q000378:metabolism*; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology*; D009599:Nitroprusside / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D003497:Cyclic N-Oxides; D005290:Ferric Compounds; D005292:Ferricyanides; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D007093:Imidazoles; D008903:Minerals; D020030:Nitric Oxide Donors; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; C110881:S-nitro-N-acetylpenicillamine; D009599:Nitroprusside; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D008353:Mannitol; D026422:S-Nitrosoglutathione; D015764:Bepridil; C038178:ammonium ferrous sulfate; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D010396:Penicillamine; C049467:ammonium ferric sulfate; D002118:Calcium