Received for publication February 10, 2006.
Revised February 10, 2006.
Accepted for publication February 13, 2006.

No NO for HO-1 from SNP (Relates to Article by Kim, et al. FastForward 26 January 2006)

Abstract

Nitric oxide (NO) and NO donors where 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. 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 by Kim et al., 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.

Key words: Guanylyl cyclase, Nitric oxide, Adenylyl cyclases, cAMP, cGMP, Protein Kinase A, MAP Kinase, Heme metabolism, Oxidative stress/antioxidants