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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 (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 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 Bruene, B. Search for Related Content PubMed PubMed Citation Articles by Shatrov, V. A Articles by Bruene, B. Social Bookmarking                   What's this? Submitted September 5, 2002 Accepted February 3, 2003 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 Bruene* Cell Biology, University of Kaiserslautern, Kaiserslautern, Germany * Corresponding author; email: bruene{at}rhrk.uni-kl.de. Oxidized low density lipoprotein (oxLDL) and macrophages play a central role in atherosclerosis. Here we obtained evidence that oxLDL induced HIF-1 protein accumulation in human macrophages (Mono-Mac-6) under normoxia. HIF-1 accumulation was attenuated by pre-treatment with the antioxidant N-acetyl-L-cysteine (NAC), the NO donor S-nitrosoglutathione (GSNO), and 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. Taken together, 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 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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