Angiotensin II-Induced Regulation of the Expression and Localization of Iron Metabolism-Related Genes in the Rat Kidney

Abstract

Due to recent discoveries of novel genes involved in iron metabolism, our understanding of the molecular mechanisms underlying iron metabolism has dramatically increased. We have previously shown that the administration of angiotensin II alters iron homeostasis in the rat kidney, which may in turn aggravate angio-

Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells

“…HGECs were plated in 75-cm 2 type collagen-coated flasks (Becton Dickinson Labware, Lincoln Park, NJ, USA) after thawing, and cultured in 10% serum CSC complete medium (Cell Systems) without antibiotics. The cells were grown in a humidified atmosphere in 5% CO 2 and 95% air at 37 1C. The medium was changed every 2 days.…”

“…As shown in Figure 1a, co-treatment with 1 nM Ang II and 50 mM 30% Tf for 24 h resulted in a significant increase in intracellular iron concentration (control: 0. Time course for the protein expression of TfR, DMT1 and FPN1 in HGECs stimulated by Ang II As administration of Ang II to rats increased TfR, DMT1 and FPN1 mRNA levels in the kidney, 2 we examined the effect of 1 nM Ang II on iron metabolism-related protein levels in HGECs. As shown in Figure 2a, bands representing TfR, DMT1 and FPN1 proteins were recognized at 95 kDa, 65 kDa and 60 kDa, respectively.…”

“…Ang II is a critical peptide in blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, and it has been implicated in the pathophysiology of hypertension, congestive heart failure, diabetic nephropathy and vascular diseases, including atherosclerosis. 1 In addition, Ishizaka et al 2 reported that 7-day Ang II infusion with an osmotic minipump-induced mRNA expression of iron metabolism-related genes, including transferrin receptor (TfR), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1) and hepcidin, in the rat kidney.…”

“…24,25 Furthermore, O 2 À oxidizes and (4Fe-4S) clusters of dehydratases, such as aconitases and fumarase A and B, and this oxidation process facilitates iron release in the ferrous form, and then the liberated ferrous iron participates in the Fenton reaction. 25 Similarly, ferritin 26 and Tf 27 release ferrous iron by O 2 À . It has been established that Ang II-induced oxidative stress depends on the generation of O 2 À by activation of NADP(H) oxidases through the Ang II type 1 (AT 1 ) receptor.…”

“…It has been established that Ang II-induced oxidative stress depends on the generation of O 2 À by activation of NADP(H) oxidases through the Ang II type 1 (AT 1 ) receptor. 28,29 However, we hypothesized that Ang II induces not only O 2 À production but also iron incorporation into cells and facilitates ferrous iron formation. These in turn interact with each other to promote cell dysfunctions through the iron-mediated ROS generation system.…”