The Effect of Redox-Related Species of Nitrogen Monoxide on Transferrin and Iron Uptake and Cellular Proliferation of Erythroleukemia (K562) Cells

The iron-responsive lement-binding protein (IRE-BP) modulates both ferritin mRNA translation and transferrin receptor (TfR) mRNA stability by binding to specific mRNA sequences called iron-responsive elements (IRES). The regulation of IREBP in situ auld possibly occur either through its Fe-S cluster and/or via free cysteine sulphydryl groups such as cysteine 437 (Philpott et al, J Biol Chem 268A7655.1993; and Hirling et al, EMBO J 13:453, 1994). Recently, nitrogen monoxide (NO) has been shown to have markedly different biologic effects depending on its redox state (Lipton et al. Nature 364626, 1993). Considering this fact, it is conceivable that the NO group, as either the nitrosonium ion (NO') or nitric oxide (NO), may regulate IRE-BP activity by S-nitrosylation of key sulphydryl groups or via ligation of NO to the FeS cluster, respectively. This hypothesis has been examined using the NO+ generator, sodium nitroprusside (SNP); the N O generator, S-nitroso-N-acetylpenicillamine (SNAP); and