A drastic superoxide-dependent oxidative stress is prerequisite for the down-regulation of IRP1: Insights from studies on SOD1-deficient mice and macrophages treated with paraquat.

ABSTRACT: Iron regulatory protein 1 (IRP1) is a cytosolic bifunctional [4Fe-4S] protein which exhibits aconitase activity or binds iron responsive elements (IREs) in untranslated regions of specific mRNA encoding proteins involved in cellular iron metabolism. Superoxide radical (O2.-) converts IRP1 from a [4Fe-4S] aconitase to a [3Fe-4S] "null" form possessing neither aconitase nor trans-regulatory activity. Genetic ablation of superoxide dismutase 1 (SOD1), an antioxidant enzyme that acts to reduce O2.- concentration, revealed a new O2.--dependent regulation of IRP1 leading to the reduction of IRP1 protein level and in consequence to the diminution of IRP1 enzymatic and IRE-binding activities. Here, we attempted to establish whether developmental changes in SOD1 activity occurring in the mouse live

SUBMITTER: Milczarek A 

PROVIDER: S-EPMC5438123 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature