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. Expression of the placental Cu oxidase is inversely proportional to Fe status and directly proportional to Cu status at enzyme and protein levels. To identify a role for the Cu oxidase, cells were exposed to (59)Fe-transferrin for 18 h in an environment of 20% O(2) or 5% O(2). At 5% O(2), Cu-deficient cells retain significantly more (59)Fe than control cells. This excess in (59)Fe accumulation is caused by a significant decrease in (59)Fe release. These results indicate that downregulation of the placental Cu oxidase in BeWo cells impairs Fe release. This effect is only apparent in an environment of limited O(2).
Danzeisen
Ruth
R
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, United Kingdom.
Fosset
Cedric
C
Chariana
Zehane
Z
Page
Kenneth
K
David
Samuel
S
McArdle
Harry J
HJ
D000818:Animals; D002458:Cell Fractionation; D002570:Ceruloplasmin / Q000031:analogs & derivatives / Q000378:metabolism*; D002822:Choriocarcinoma; D003300:Copper / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010655:Phenylenediamines / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D006571:Heterocyclic Compounds; D007502:Iron Chelating Agents; D010655:Phenylenediamines; D003300:Copper; C059143:diamsar chelate; D007501:Iron; D010088:Oxidoreductases; C024748:copper oxidase; D002570:Ceruloplasmin; D003676:Deferoxamine; D010100:Oxygen; D012521:Sarcosine