Ceruloplasmin expression and its role in iron transport in C6 cells.
Ceruloplasmin (CP) is essential for brain iron homeostasis. However, little is known about the effect of iron on CP expression in the brain. Also, the role of CP in brain iron transport has not been well determined. In this study, we investigated the effects of iron on CP expression and the role of CP in iron transport in the C6 rat glioma cells. Our data showed that treatment of the cells with iron (cell iron overload) or iron chelators (cell iron deficiency) did not induce a significant change in the expression of CP mRNA. However, western blotting analysis demonstrated that cell iron overload induced a significant decrease in CP protein content in the cells and that treatment with iron chelators led to a significant increase in CP protein level in the cells. These findings suggest a translational regulation of CP expression by iron in the cells. We also examined the effects of CP on iron transport in the cells. We found that glycosylphosphatidylinositol-anchored CP did not have any impact on iron uptake by normal iron or iron-deficient cells nor on iron release from normal iron or iron-sufficient cells. However, low concentrations of soluble CP (2-8 microg/ml) increased iron uptake by iron-deficient C6 glioma cells, while the same concentrations of CP had no effect on iron uptake by normal iron cells and iron release from normal iron and iron-sufficient cells. The possible reason for the difference between our results in vitro and those obtained from in vivo studies was discussed.
Chang
Yan Zhong
YZ
Laboratory of Brain Iron Metabolism, Department of Applied Biology & Chemical Technology, and National Key Laboratory of Chinese Medicine and Molecular Pharmacology (Shenzhen), Hong Kong Polytechnic University, Kowloon, Hong Kong, PR China.
Qian
Zhong Ming
ZM
Du
Jin Rong
JR
Zhu
Li
L
Xu
Youjia
Y
Li
Lian-Zhi
LZ
Wang
Chen-Yuen
CY
Wang
Qin
Q
Ge
Xiao Hu
XH
Ho
Kwok Ping
KP
Niu
Lijin
L
Ke
Ya
Y
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002570:Ceruloplasmin / Q000096:biosynthesis* / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011990:Receptors, Transferrin / Q000096:biosynthesis
D007502:Iron Chelating Agents; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D007501:Iron; D002570:Ceruloplasmin