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Titre du document / Document title

Tumor necrosis factor-α-induced iron sequestration and oxidative stress in human endothelial cells

Auteur(s) / Author(s)

NANAMI Masayoshi (1) ; OOKAWARA Tomomi (2) ; OTAKI Yoshinaga (1) ; ITO Katsukiyo (1) ; MORIGUCHI Rintarou (1) ; MIYAGAWA Koji (1) ; HASUIKE Yukiko (1) ; IZUMI Masaaki (1) ; EGUCHI Hironobu (2) ; SUZUKI Keiichiro (2) ; NAKANISHI Takeshi (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Hyogo, JAPON
(2) Department of Biochemistry, Hyogo College of Medicine, Hyogo, JAPON

Résumé / Abstract

Objective-Tumor necrosis factor (TNF)-α-induced endothelial injury, which is associated with atherosclerosis, is mediated by intracellular reactive oxygen species. Iron is essential for the amplification of oxidative stress. We tested whether TNF-a accelerated iron accumulation in vascular endothelium, favoring synthesis of hydroxyl radical. Methods and Results-Diverse iron transporters, including iron import proteins (transferrin receptor [TfR] and divalent metal transporter 1 [DMT1]) and an iron export protein (ferroportin 1 [FP1]) coexist in human umbilical endothelial cells (HUVECs). TNF-α caused upregulation of TfR and DMT1 and downregulation of FP1, which were demonstrated in mRNA as well as protein levels. These changes in iron transporters were accompanied by accumulation of iron that was both transferrin-dependent and transferrin-independent. Modifications of these mRNAs were regulated post-transcriptionally, and were coordinated with activation of binding activity of iron regulatory protein 1 to the iron responsive element on transporter mRNAs. Using a salicylate trap method, we observed that only simultaneous exposure of endothelial cells to iron and TNF-a accelerated hydroxyl radical production. Conclusions-TNF-a could cause intracellular iron sequestration, which may participate importantly in the pathophysiology of atherosclerosis and cardiovascular disease.

Revue / Journal Title

Arteriosclerosis, thrombosis, and vascular biology    ISSN  1079-5642   CODEN ATVBFA 

Source / Source

2005, vol. 25, no12, pp. 2495-2501 [7 page(s) (article)] (37 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott Williams & Wilkins, Philadelphia, PA, ETATS-UNIS  (1995) (Revue)

Mots-clés anglais / English Keywords

Vascular disease

;

Inflammation

;

Free radical

;

Endothelium

;

Cytokine

;

Endothelial cell

;

Human

;

Oxidative stress

;

Iron

;

Tumor necrosis factor α

;

Atherosclerosis

;

Cardiovascular disease

;

Mots-clés français / French Keywords

Vaisseau sanguin pathologie

;

Inflammation

;

Radical libre

;

Endothélium

;

Cytokine

;

Cellule endothéliale

;

Homme

;

Stress oxydatif

;

Fer

;

Facteur nécrose tumorale α

;

Athérosclérose

;

Appareil circulatoire pathologie

;

Mots-clés espagnols / Spanish Keywords

Vaso sanguíneo patología

;

Inflamación

;

Radical libre

;

Endotelio

;

Citoquina

;

Célula endotelial

;

Hombre

;

Estrés oxidativo

;

Hierro

;

Factor necrosis tumoral α

;

Ateroesclerosis

;

Aparato circulatorio patología

;

Mots-clés d'auteur / Author Keywords

cytokines

;

endothelium

;

free radicals

;

inflammation

;

iron

;

Localisation / Location

INIST-CNRS, Cote INIST : 19104, 35400013446720.0090

Nº notice refdoc (ud4) : 17328512



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