title: Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells.
abstract: Angiotensin II (Ang II)-induced endothelial injury, which is associated with atherosclerosis, is believed to be mediated by intracellular reactive oxygen species (ROS) through stimulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX). Iron is essential for the amplification of oxidative stress. In this study, we investigated whether Ang II altered iron metabolism and whether the Ang II-induced endothelial injury is attributable to changes in iron metabolism of human glomerular endothelial cells (HGECs). When 90% iron-saturated human transferrin (90% Tf) was applied to HGECs without Ang II, the labile ferrous iron level was same as the effect of control in spite of a significant increase in the total cellular iron concentration. Treatment with Ang II and 30% Tf or 90% Tf significantly (P<0.01) increased the intracellular iron concentration, as well as labile ferrous iron and protein oxidation levels, compared with the effect of separate administration of each compound. Ang II treatment facilitated the protein expression of the Tf receptor, divalent metal transporter 1, and ferroportin 1 in a dose- and time-dependent manner. It was also found that simultaneous exposure of HGECs to Ang II and 90% Tf accelerated hydroxyl radical production, as shown by using an electron paramagnetic resonance spectrometer. These results suggest that Ang II not only induces production of ROS by NOX activation but also iron incorporation followed by an increase in labile iron in HGECs. Both of these events may participate in the progression of oxidative stress because of endothelial cell dysfunction through ferrous iron-mediated ROS generation.
authors.affiliation: Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Tajima
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Yuya
authors.initials: Y
authors.lastname: Horinouchi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shono
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000032:analysis; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017665:Hydroxyl Radical / Q000032:analysis; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D011990:Receptors, Transferrin / Q000032:analysis; D014168:Transferrin / Q000378:metabolism*; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D000804:Angiotensin II; D027682:Cation Transport Proteins; D017665:Hydroxyl Radical; D007501:Iron; D011990:Receptors, Transferrin; D014168:Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2