Cu loading alters expression of non-IRE regulated, but not IRE regulated, Fe dependent proteins in HepG2 cells.

This paper investigates the extent to which Cu loading influences Fe levels in HepG2 cells and the effect on proteins regulated by Fe status. Cu supplementation increased Cu content 3-fold, concomitant with a decrease in cellular Fe levels. Intracellular levels of both transferrin (Tf) and ceruloplasmin (Cp) protein rose in parallel with increased secretion into the culture media.

Regulation of the cysteine desulfurase Nfs1 and the scaffold protein IscU in macrophages stimulated with interferon-gamma and lipopolysaccharide.

Biogenesis of iron-sulfur (Fe-S) clusters in mammals involves a complex mitochondrial machinery that provides inorganic sulfide and iron for their assembly and insertion into apo-proteins. Mechanisms of Fe-S cluster assembly are just being unraveled, and regulation of the genes of this machinery remains unknown. In this study, we report that expression of two essential components of the Fe-S machinery, the cysteine desulfurase Nfs1 and its scaffold protein partner IscU, is down-regulated at both mRNA and protein levels when murine macrophages are physiologically stimulated with IFN-gamma and LPS.

RNA silencing of mitochondrial m-Nfs1 reduces Fe-S enzyme activity both in mitochondria and cytosol of mammalian cells.

In prokaryotes and yeast, the general mechanism of biogenesis of iron-sulfur (Fe-S) clusters involves activities of several proteins among which IscS and Nfs1p provide, through cysteine desulfuration, elemental sulfide for Fe-S core formation. Although these proteins have been well characterized, the role of their mammalian homolog in Fe-S cluster biogenesis has never been evaluated. We report here the first functional study that implicates the putative cysteine desulfurase m-Nfs1 in the biogenesis of both mitochondrial and cytosolic mammalian Fe-S proteins.

Interrelations between ceruloplasmin and Fe status during human pregnancy.

It is well established that Fe and ceruloplasmin interact in animals and in in vitro models. However, Fe-mediated regulation of ceruloplasmin has never been investigated in humans. In an observational study, 53 pregnant women aged 19-39 yr (29.

Iron and copper interactions in development and the effect on pregnancy outcome.

During pregnancy, nutrients are transferred from mother to fetus across the placenta. The mechanisms whereby this occurs, and the adaptations that occur in response to deficiency or overload of iron (Fe) and copper (Cu) are examined in this review. Fe deficiency during pregnancy is common and has serious consequences both in the short and the long term such as fetal growth retardation and cardiovascular problems in the adult offspring.

Placental ceruloplasmin homolog is regulated by iron and copper and is implicated in iron metabolism.

We previously reported an endogenous, membrane-bound Cu oxidase with homology to ceruloplasmin in BeWo cells, a placental choriocarcinoma cell line. In this previous study, ceruloplasmin immunoreactivity was localized to the perinuclear region and non-brush-border membranes. Here, we show that azide-sensitive oxidase activity is enriched in the same fractions, correlating subcellular localization of enzyme activity with ceruloplasmin immunoreactivity.