Os. Chen et al., DIETARY IRON INTAKE MODULATES THE ACTIVITY OF IRON REGULATORY PROTEINS AND THE ABUNDANCE OF FERRITIN AND MITOCHONDRIAL ACONITASE IN RAT-LIVER, The Journal of nutrition, 127(2), 1997, pp. 238-248
Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding
proteins that coordinate cellular iron homeostasis in mammals, We inve
stigated the effect of dietary iron intake on rat liver IRP activity i
n relation to the abundance of two targets of IRP action, ferritin and
mitochondrial aconitase (m-aconitase), Rats were fed diets containing
2, 11, 20, 37 (control), 72 or 107 mg iron/kg diet for 3 wk, RNA bind
ing activity of IRP1 and IRP2 was enhanced one- to twofold in rats fed
11 or 2 mg iron/kg diet compared with control rats, IRP RNA binding a
ctivity was inversely correlated to blood hemoglobin levels (r = -0.78
7; P < 0.0001), Compared with control rats, liver ferritin levels were
depressed in rats fed 20 mg iron/kg diet and were undetectable in rat
s ingesting diets with II or 2 mg iron/kg diet, Ferritin concentration
s were biphasically related to IRP RNA binding activity with the regul
ation of IRP occurring before the onset of ferritin accumulation. Iron
deficiency caused up to a 50% decline in m-aconitase abundance, IRP R
NA binding activity and m-aconitase abundance were inversely correlate
d (r = -0.751; P < 0.0001), Our results indicate that (1) liver IRP ac
tivity is responsive to a range of dietary iron levels, (2)there appea
rs to be a differential effect of IRPs on ferritin and m-aconitase abu
ndance, and (3) activation of IRPs may contribute to the alterations i
n energy metabolism in iron deficiency through an impairment of m-acon
itase synthesis.