Comparison of non-heme liver iron and iron metabolism protein levels in superoxide dismutase 1 knock-out mice versus superoxide dismutase 1 wild-type mice
Eisenstein, Richard S.
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Iron is an important micronutrient that is necessary for multiple cellular functions. However, iron levels must be tightly regulated in order to prevent iron-deficiency and iron-toxicity. There are many proteins involved in iron metabolism. This study focuses on iron-regulatory proteins 1 and 2 (IRP1/2), ferritin, and transferrin receptor protein (TfR). IRPs are key iron sensors that bind to iron response elements (IREs) located on mRNA when the IRP Fe-S clusters are removed, regulating translation or stability of mRNA. Ferritin is the storage form of iron. Ferritin levels must increase in iron-sufficient or overloaded conditions to store the excess iron in a safe form. TfR takes up iron and moves it into a free iron pool for utilization by the body. TfR levels must increase in iron-deficient conditions to mobilize iron to necessary tissues. When IRP binds to a ferritin IRE, ferritin mRNA translation is inhibited causing ferritin protein levels to decrease. However, when IRP binds to TfR IRE, TfR mRNA is stabilized causing TfR protein levels to increase. Reactive oxygen species (ROS) such as the superoxide anion have been known to destabilize the Fe-S cluster in IRP, possibly leading to IRP degradation in high concentrations of ROS. Superoxide dismutase 1 (SOD1) reacts with the superoxide anion to yield safer complexes (hydrogen peroxide and water). I hypothesized that SOD1 knock-out (KO) mice would have increased non-heme liver iron and ferritin levels as well as decreased TfR and IRP1/2 levels due to the increased levels of superoxide anions removing the Fe-S clusters, decreasing IRP/IRE TfR and ferritin mRNA binding. My data supported my hypothesis. I used a non-heme liver assay, hematocrit measurements, and western blots to measure the levels of non-heme liver iron and protein levels in KO and WT male mice (C57BU61 background) at ages 8 weeks, 2.5-3 months, 4 months, 6 months, and 12 months.