Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rossmann, C; Rauh, A; Hammer, A; Windischhofer, W; Zirkl, S; Sattler, W; Malle, E.
Hypochlorite-modified high-density lipoprotein promotes induction of HO-1 in endothelial cells via activation of p42/44 MAPK and zinc finger transcription factor Egr-1.
Arch Biochem Biophys. 2011; 509(1):16-25
Doi: 10.1016/j.abb.2011.02.016
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- Führende Autor*innen der Med Uni Graz
- Malle Ernst
- Rossmann Christine Renate
- Co-Autor*innen der Med Uni Graz
- Hammer Astrid
- Windischhofer Werner
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- Abstract:
- Modification/chlorination of high-density lipoprotein (HDL) by hypochlorous acid (HOCl), formed by the myeloperoxidase-H₂O₂-chloride system of activated phagocytes, converts an anti-atherogenic lipoprotein into a pro-inflammatory lipoprotein particle. Chlorinated HDL is present in human lesion material, binds to and is internalized by endothelial cells and impairs expression and activity of endothelial nitric oxide synthase. The present study aimed at clarifying whether exposure of endothelial cells to pro-inflammatory HOCl-HDL impacts on expression of heme oxygenase-1, a potential rescue pathway against endothelial dysfunction. Our findings revealed that HDL modified by HOCl, added as reagent or generated enzymatically, induced phosphorylation of p42/44 mitogen-activated protein kinase, expression of transcription factor early growth response-1 (Egr-1) and enhanced expression of heme oxygenase-1 in human endothelial cells. Upregulation of heme oxygenase-1 could be blocked by an inhibitor upstream of p42/44 mitogen-activated protein kinase and/or knockdown of Egr-1 by RNA-interference. Electrophoretic mobility shift assays demonstrated HOCl-HDL-mediated induction of the Egr-1 DNA binding activity. Immunocytochemical and immunoblotting experiments demonstrated HOCl-HDL-induced translocation of Egr-1 to the nucleus. The present study demonstrates a novel compensatory pathway against adverse effects of HOCl-HDL, providing cytoprotection in a number of pathological conditions including cardiovascular disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line -
- Early Growth Response Protein 1 - analysis
- Electrophoretic Mobility Shift Assay -
- Endothelial Cells - cytology
- Gene Expression Regulation -
- Heme Oxygenase-1 - genetics
- Humans -
- Hypochlorous Acid - immunology
- Immunochemistry -
- Lipoproteins, HDL - immunology
- Mitogen-Activated Protein Kinase 1 - genetics
- Mitogen-Activated Protein Kinase 3 - genetics
- Protein Transport -
- Zinc Fingers -
- p38 Mitogen-Activated Protein Kinases - genetics
- Find related publications in this database (Keywords)
- Chlorinated HDL
- Hypochlorous acid
- Inflammation
- Myeloperoxidase
- MPO-H2O2-chloride system
- Nrf2