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SHR Neuro Krebs Kardio Lipid

Marsche, G; Semlitsch, M; Hammer, A; Frank, S; Weigle, B; Demling, N; Schmidt, K; Windischhofer, W; Waeg, G; Sattler, W; Malle, E.
Hypochlorite-modified albumin colocalizes with RAGE in the artery wall and promotes MCP-1 expression via the RAGE-Erk1/2 MAP-kinase pathway.
FASEB J. 2007; 21(4): 1145-1152. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Frank Saša
Hammer Astrid
Malle Ernst
Marsche Gunther
Sattler Wolfgang
Semlitsch Michaela
Windischhofer Werner
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Number of Figures: 4
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Abstract:
Signal transduction via the endothelial receptor for advanced glycation end products (RAGE) plays a key role in vascular inflammation. Recent observations have shown that the myeloperoxidase-H2O2-chloride system of activated phagocytes is highly up-regulated under inflammatory conditions where hypochlorous acid (HOCl) is formed as the major oxidant. Albumin, an in vivo carrier for myeloperoxidase is highly vulnerable to oxidation and a major representative of circulating advanced oxidized proteins during inflammatory diseases. Immunohistochemical studies performed in the present study revealed marked colocalization of HOCl-modified epitopes with RAGE and albumin in sections of human atheroma, mainly at the endothelial lining. We show that albumin modified with physiologically relevant concentrations of HOCl, added as reagent or generated by the myeloperoxidase-H2O2-chloride system, is a high affinity ligand for RAGE. Albumin, modified by HOCl in the absence of free amino acids/carbohydrates/lipids to exclude formation of AGE-like structures, induced a rapid, RAGE-dependent activation of extracellular signal-regulated kinase 1/2 and up-regulation of the proinflammatory mediator monocyte chemoattractant protein-1. Cellular activation could be blocked either by a specific polyclonal anti-RAGE IgG and/or a specific mitogen-activated protein-kinase kinase inhibitor. The present study demonstrates that HOCl-modified albumin acts as a ligand for RAGE and promotes RAGE-mediated inflammatory complications.
Find related publications in this database (using NLM MeSH Indexing)
Albumins - chemistry
Arteries - metabolism
Cell Line - metabolism
Chemokine CCL2 - biosynthesis
Gene Expression Regulation - biosynthesis
Humans - biosynthesis
Hypochlorous Acid - pharmacology
Inflammation - pharmacology
MAP Kinase Signaling System - pharmacology
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Peroxidase - metabolism
Receptors, Immunologic - metabolism
Signal Transduction - metabolism

Find related publications in this database (Keywords)
AOPP
hypochlorous acid
inflammation
myeloperoxidase
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