Nitrosative and oxidative modulation of iron regulatory proteins

Abstract.

Cytokine-driven nitric oxide (NO) synthase II provides cells with effectors for reactions at redox-sensitive site(s) of proteins. Iron regulatory proteins (IRP1 and IRP2), two post-transcriptional regulators of gene expression, are particularly sensitive to NO synthesis and to oxidative stress. IRP1 possesses a redox-active Fe-S cluster and can also exhibit aconitase activity. IRP2 has no Fe-S cluster but exhibits several redox-sensitive cysteine residues. Under proper redox conditions, both IRPs bind to iron-responsive elements in the untranslated region of mRNAs encoding proteins involved in iron metabolism and energy production. This review describes and compares the effects of NO, peroxynitrite, and reactive oxygen species on these two chemosensitive proteins.