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Hypochlorous acid stimulates heme oxygenase‐1 gene expression in vascular endothelium
Author(s) -
Wei Yong,
Liu Xiaoming,
Peyton Kelly J.,
Wang Hong,
Durante William
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.964.7
Subject(s) - hypochlorous acid , heme oxygenase , umbilical vein , heme , chemistry , endothelium , myeloperoxidase , gene expression , biochemistry , endothelial stem cell , messenger rna , microbiology and biotechnology , enzyme , gene , biology , immunology , inflammation , in vitro , endocrinology
Hypochlorous acid (HOCl) is the major product of the enzyme myeloperoxidase which is active in human atherosclerotic lesions and often closely associated with endothelial cells. HOCl is a potent antimicrobial oxidant that plays an important role in host defense; however, it may also contribute to tissue injury. In the present study, we examined whether HOCl regulates the expression of the cytoprotective protein heme oxygenase‐1 (HO‐1) in human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with HOCl (3–300μM) stimulated a concentration‐ and time‐dependent increase in HO‐1 protein. A significant rise in HO‐1 protein was first detected after 4 hours and levels progressively increased over 24 hours of HOCl exposure. HOCl‐mediated increases in HO‐1 protein were preceded by significant elevations in HO‐1 mRNA that peaked 4 to 8 hours after HOCl treatment. The induction of HO‐1 by HOCl was dependent on de novo RNA synthesis since it was blocked by the transcriptional inhibitor, actinomycin D (2ìg/ml). In addition, HO‐1 expression was inhibited by the antioxidant N‐acetyl‐L‐cysteine (10mM). In conclusion, this study demonstrates that HOCl stimulates HO‐1 gene expression in vascular endothelium via a transcriptional‐ and redox‐sensitive pathway. The ability of HOCl to induce HO‐1 may represent a critical adaptive response to preserve cell viability at sites of atherosclerosis. Supported by NIH.