RT Journal Article
SR Electronic
T1 No Nitric Oxide for HO-1 from Sodium Nitroprusside
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1507
OP 1509
DO 10.1124/mol.106.023416
VO 69
IS 5
A1 Henning Schröder
YR 2006
UL http://molpharm.aspetjournals.org/content/69/5/1507.abstract
AB Nitric oxide (NO) and NO donors were among the first reported inducers of the tissue-protective protein heme oxygenase-1 (HO-1) with a potential for eventual use in humans. Besides other clinically established NO releasing drugs, sodium nitroprusside (SNP) has frequently been employed as an experimental tool to explore effects of NO on HO-1 and other biological targets. In this issue of Molecular Pharmacology, Kim et al. (p. 1633) demonstrate that the effects of SNP on expression of HO-1 are mainly due to free iron released from SNP in aqueous solution, whereas NO plays a negligible role, if any, as the mediator of response to SNP. Downstream effects of iron, after being dissociated from SNP, include increases in intracellular cAMP that are causally linked to subsequent phosphorylation of specific MAPK targets and enhanced HO-1 protein levels. Based on the data reported by Kim et al. (2006), the use of SNP as an experimental tool to mimic intracellular effects of NO should be avoided in the future. This work not only helps revise concepts in NO and HO-1 research but also may direct future efforts to the role of iron and reactive oxygen species in the regulation of adenylyl cyclase.