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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-09-2711. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2711v1 101/12/4847    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shatrov, V. A. Articles by Brüne, B. Search for Related Content PubMed PubMed Citation Articles by Shatrov, V. A. Articles by Brüne, B. Related Collections Gene Expression Brief Reports Hemostasis, Thrombosis, and Vascular Biology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 4847-4849 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1 (HIF-1) accumulation via redox-dependent mechanisms Vladimir A. Shatrov, Vadim V. Sumbayev, Jie Zhou, and Bernhard Brüne From the Faculty of Biology, Department of Cell Biology, University of Kaiserslautern, Germany. Oxidized low-density lipoprotein (oxLDL) and macrophages play a central role in atherosclerosis. Here, we obtained evidence that oxLDL induced hypoxia-inducible factor-1 (HIF-1) protein accumulation in human macrophages (Mono-Mac-6) under normoxia. HIF-1 accumulation was attenuated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC), the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors such as diphenyleniodonium (DPI) or 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), thus implicating the contribution of oxLDL-generated reactive oxygen species (ROS). Whereas oxLDL did not modulate HIF-1 mRNA levels, experiments with cycloheximide pointed to a translational mechanism in oxLDL action. HIF-1–dependent luciferase reporter gene analysis underscored HIF-1 transactivation. Our results indicate that oxLDL induced HIF-1 accumulation and HIF-1–dependent reporter gene activation in human macrophages via a redox-mediated pathway. This finding may suggest a role of HIF-1 in atherosclerosis and oxLDL-induced pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. V. Oskolkova, T. Afonyushkin, A. Leitner, E. von Schlieffen, P. S. Gargalovic, A. J. Lusis, B. R. Binder, and V. N. Bochkov ATF4-dependent transcription is a key mechanism in VEGF up-regulation by oxidized phospholipids: critical role of oxidized sn-2 residues in activation of unfolded protein response Blood, July 15, 2008; 112(2): 330 - 339. [Abstract] [Full Text] [PDF] M. Mayr, A. Sidibe, and A. Zampetaki The Paradox of Hypoxic and Oxidative Stress in Atherosclerosis J. Am. Coll. Cardiol., April 1, 2008; 51(13): 1266 - 1267. [Full Text] [PDF] T. Oda, K. Hirota, K. Nishi, S. Takabuchi, S. Oda, H. Yamada, T. Arai, K. Fukuda, T. Kita, T. Adachi, et al. Activation of hypoxia-inducible factor 1 during macrophage differentiation Am J Physiol Cell Physiol, July 1, 2006; 291(1): C104 - C113. [Abstract] [Full Text] [PDF] H. J. Knowles, D. R. Mole, P. J. Ratcliffe, and A. L. Harris Normoxic Stabilization of Hypoxia-Inducible Factor-1{alpha} by Modulation of the Labile Iron Pool in Differentiating U937 Macrophages: Effect of Natural Resistance-Associated Macrophage Protein 1. Cancer Res., March 1, 2006; 66(5): 2600 - 2607. [Abstract] [Full Text] [PDF] M. Slevin, A. B. Elasbali, M. Miguel Turu, J. Krupinski, L. Badimon, and J. Gaffney Identification of Differential Protein Expression Associated with Development of Unstable Human Carotid Plaques Am. J. Pathol., March 1, 2006; 168(3): 1004 - 1021. [Abstract] [Full Text] [PDF] C. Murdoch, M. Muthana, and C. E. Lewis Hypoxia Regulates Macrophage Functions in Inflammation J. Immunol., November 15, 2005; 175(10): 6257 - 6263. [Abstract] [Full Text] [PDF] J. W. Zmijewski, D. R. Moellering, C. L. Goffe, A. Landar, A. Ramachandran, and V. M. Darley-Usmar Oxidized LDL induces mitochondrially associated reactive oxygen/nitrogen species formation in endothelial cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H852 - H861. [Abstract] [Full Text] [PDF] G. Chachami, G. Simos, A. Hatziefthimiou, S. Bonanou, P.-A. Molyvdas, and E. Paraskeva Cobalt Induces Hypoxia-Inducible Factor-1{alpha} Expression in Airway Smooth Muscle Cells by a Reactive Oxygen Species- and PI3K-Dependent Mechanism Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 544 - 551. [Abstract] [Full Text] [PDF]

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