title: Abnormal iron deposition in renal cells in the rat with chronic angiotensin II administration.
abstract: Acute experimental iron loading causes iron to accumulate in the renal tissue. The accumulation of iron may play a role in enhancing oxidant-induced tubular injury by producing increased amounts of reactive oxygen species. From findings in cells from heme oxygenase-1 (HO-1)-deficient mice, HO-1 is postulated to prevent abnormal intracellular iron accumulation. Recently, it has been reported that HO-1 is induced in the renal tubular epithelial cells, in which iron is deposited after iron loading, and that this HO-1 induction may be involved in ameliorating iron-induced renal toxicity. We previously showed that chronic administration of angiotensin II to rats induces HO-1 expression in the tubular epithelial cells. These observations led us to investigate whether there is a link between iron deposition and HO-1 induction in renal tubular cells in rats undergoing angiotensin II infusion. In the present study, rats were given angiotensin II for continuously 7 days. Prussian blue staining revealed the distinct deposits of iron in the proximal tubular epithelial cells after angiotensin II administration. Electron microscopy demonstrated that iron particles were present in the lysosomes of these cells. Histologic and immunohistochemical analyses showed that stainable iron and immunoreactive ferritin and HO-1 were colocalized in the tubular epithelial cells. Treatment of angiotensin II-infused rats with an iron chelator, deferoxamine, blocked the abnormal iron deposition in kidneys and also the induced expression of HO-1 and ferritin expression. Furthermore, deferoxamine treatment suppressed the angiotensin II-induced increase in the urinary excretion of protein and N-acetyl-beta-D-glucosaminidase, a marker of tubular injury; however, deferoxamine did not affect the angiotensin II-induced decrease in glomerular filtration rate. These results suggest that angiotensin II causes renal injury, in part, by inducing the deposition of iron in the kidney.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. nobuishizka-tky@umin.ac.jp
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
authors.forename: Toru
authors.initials: T
authors.lastname: Aizawa
authors.forename: Ieharu
authors.initials: I
authors.lastname: Yamazaki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Usui
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Shiow-Shih
authors.initials: SS
authors.lastname: Tang
authors.forename: Julie R
authors.initials: JR
authors.lastname: Ingelfinger
authors.forename: Minoru
authors.initials: M
authors.lastname: Ohno
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000804:Angiotensin II / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D005293:Ferritins / Q000096:biosynthesis; D006339:Heart Rate / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency; D051547:Heme Oxygenase-1; D006439:Hemodynamics / Q000187:drug effects; D007501:Iron / Q000097:blood / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011507:Proteinuria; D051381:Rats; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D000804:Angiotensin II; D005293:Ferritins; D003404:Creatinine; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D000118:Acetylglucosaminidase