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.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Rossmann C,Rauh A,Hammer A,Windischhofer W,Zirkl S,Sattler W,Malle Edoi
10.1016/j.abb.2011.02.016subject
Has Abstractpub_date
2011-05-01 00:00:00pages
16-25issue
1eissn
0003-9861issn
1096-0384pii
S0003-9861(11)00080-4journal_volume
509pub_type
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journal_title:Archives of biochemistry and biophysics
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2010-06-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
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journal_title:Archives of biochemistry and biophysics
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pub_type: 杂志文章,随机对照试验
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journal_title:Archives of biochemistry and biophysics
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更新日期:1995-08-20 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:1993-05-01 00:00:00