Angiotensin II inhibits uptake of transferrin-bound iron but not non-transferrin-bound iron by cultured astrocytes.
The existence of all components of the renin-angiotensin system (RAS) and the iron metabolism system, and the recent findings on the functions of angiotensin II (ANGII) in peripheral iron metabolism imply that ANGII might play a role in iron homeostasis by regulating expression of iron transport proteins in the brain. Here, we investigated effects of ANGII on uptake and release of iron as well as expression of cell iron transport proteins in cultured astrocytes. We demonstrated that ANGII could significantly inhibit transferrin-bound iron (Tf-Fe) uptake and iron release as well as the expression of transferrin receptor 1 (TfR1) and the iron exporter ferroportin 1 (Fpn1) in cultured astrocytes. This indicated that the inhibitory role of ANGII on Tf-Fe uptake and iron release is mediated by its negative effect on the expression of TfR1 and Fpn1. We also provided evidence that ANGII had no effect on divalent metal transporter 1 (DMT1) expression as well as non-transferrin-bound iron (NTBI) uptake in the cells. Our findings showed that ANGII has a role to affect expression of iron transport proteins in astrocytes in vitro and also suggested that ANGII might have a physiological function in brain iron homeostasis.
Laboratory of Neuropharmacology and Department of Neurosurgery, South-west Hospital, The Third Military Medical University, Chongqing 400038, China.
Suna
S
Huang
Laboratory of Neuropharmacology and Department of Neurosurgery, South-west Hospital, The Third Military Medical University, Chongqing 400038, China.
Fang
F
Du
Laboratory of Neuropharmacology and Department of Neurosurgery, South-west Hospital, The Third Military Medical University, Chongqing 400038, China.
Lan
L
Li
Department of Neurology, Xin Qiao Hospital, The Third Military Medical University, Chongqing 400038, China.
Yong
Y
Liu
Laboratory of Neuropharmacology and Department of Neurosurgery, South-west Hospital, The Third Military Medical University, Chongqing 400038, China.
Yuhong
Y
Liu
Laboratory of Neuropharmacology and Department of Neurosurgery, South-west Hospital, The Third Military Medical University, Chongqing 400038, China.
Chao
C
Zhang
Laboratory of Neuropharmacology and Department of Neurosurgery, South-west Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: zhongming.qian@yahoo.com.
Zhong Ming
ZM
Qian
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D002478:Cells, Cultured; D007501:Iron / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000378:metabolism*; D000098742:Ferroportin
D027682:Cation Transport Proteins; D014168:Transferrin; D000098742:Ferroportin; D000804:Angiotensin II; D007501:Iron
Angiotensin II (ANGII); Astrocytes; Brain iron metabolism; Divalent metal transporter 1 (DMT1); Ferroportin 1 (Fpn1); Non-transferrin-bound iron (NTBI); Transferrin receptor 1 (TfR1); Transferrin-bound iron (Tf-Fe)