Transcripts of ceruloplasmin but not hepcidin, both major iron metabolism genes, exhibit a decreasing pattern along the portocentral axis of mouse liver.
OBJECTIVE
During iron overload of dietary origin, iron accumulates predominantly in periportal hepatocytes. A gradient in the basal and normal transcriptional control of genes involved in iron metabolism along the portocentral axis of liver lobules could explain this feature. Therefore, we aimed at characterizing, by quantitative RT-PCR, the expression of iron metabolism genes in adult C57BL/6 mouse hepatocytes regarding lobular localisation, with special emphasis to cell ploidy, considering its possible relationship with lobular zonation.


METHODS
We used two methods to analyse separately periportal and perivenous liver cells: 1) a selective liver zonal destruction by digitonin prior to a classical collagenase dissociation, and 2) laser capture microdissection. We also developed a method to separate viable 4N and 8N polyploid hepatocytes by flow cytometer.


RESULTS
Transcripts of ceruloplasmin, involved in iron efflux, were overexpressed in periportal areas and the result was confirmed by in situ hybridization study. By contrast, hepcidin 1, hemojuvelin, ferroportin, transferrin receptor 2, hfe and L-ferritin mRNAs were not differentially expressed according to either lobular zonation or polyploidisation level.


CONCLUSIONS
At variance with glutamine or urea metabolism, iron metabolism is not featured by a metabolic zonation lying only on a basal transcriptional control. The preferential periportal expression of ceruloplasmin raises the issue of its special role in iron overload disorders involving a defect in cellular iron export.
Troadec
Marie-Bérengère
MB
INSERM U522, University of Rennes 1, IFR 140, 35033 Rennes, France. marie-berengere.troadec@univ-rennes1.fr
Fautrel
Alain
A
Drénou
Bernard
B
Leroyer
Patricia
P
Camberlein
Emilie
E
Turlin
Bruno
B
Guillouzo
André
A
Brissot
Pierre
P
Loréal
Olivier
O
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D002570:Ceruloplasmin / Q000235:genetics*; D064451:Hepcidins; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011003:Ploidies; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D007501:Iron; D002570:Ceruloplasmin