Iron loading inhibits ferroportin1 expression in PC12 cells.
Ferroportin1 (FP1 or MTP1/IREG1), the product of the SLC40A1 gene, is a main iron export protein in mammals. Its mRNA contains an iron response element (IRE) in its 5' untranslated region, but the way this gene is regulated by iron is still unclear. The existence of FP1 in the brain has been recently confirmed. To better understand the role of this important transmembrane iron exporter in brain iron homeostasis, we investigated the effects of iron and nitric oxide (NO) on FP1 expression and that of a FP1 antibody on iron release in nerve growth factor-treated rat PC12 cells. We found that FP1 expression was down-regulated by iron loading but stimulated by iron chelation and treatment with a NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In addition, a significant decrease in iron release was found in cells treated with a FP1 antibody. Our findings imply that regulation of FP1 by iron in the cells is at the transcriptional level, rather than by an IRE/IRP-mediated pathway. Based on our results and published data, it is suggested that the transcriptional and translational (IRP/IRE pathway) mechanisms of FP1 expression might both operate in a tissue-specific manner and that FP1 might have a role in iron export from PC12 cells.
Chen
Yanmin
Y
Laboratory of Iron Metabolism, Department of Applied Biology and Chemical Technology and National Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, PR China.
Chen
Yanming
Y
Qian
Zhong-Ming
ZM
Du
Junrong
J
Duan
Xianglin
X
Chang
Yangzhong
Y
Wang
Qin
Q
Wang
Chenyuan
C
Ma
Yan Mei
YM
Xu
Youjia
Y
Li
Lianzhi
L
Ke
Ya
Y
D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016716:PC12 Cells; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D000098742:Ferroportin
D027682:Cation Transport Proteins; D002614:Chelating Agents; D005290:Ferric Compounds; D020030:Nitric Oxide Donors; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D000098742:Ferroportin; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007501:Iron; D003676:Deferoxamine; C013531:ferric ammonium citrate