Linked Life Data

19625608

Source:http://linkedlifedata.com/resource/pubmed/id/19625608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-10-2
pubmed:abstractText
Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The induction of HO-1 protein was preceded by a prominent increase in HO-1 mRNA and total and nuclear factor-erythroid 2-related factor 2 (Nrf2). In addition, HOCl induced a significant rise in HO-1 promoter activity that was blocked by mutating the antioxidant response element (ARE) in the promoter or by overexpressing a dominant-negative mutant of Nrf2. The HOCl-mediated induction of Nrf2 or HO-1 was blocked by the glutathione donor N-acetyl-l-cysteine but was unaffected by ascorbic or uric acid. Finally, treatment of endothelial cells with HOCl stimulated mitochondrial dysfunction, caspase-3 activation, and cell death that was potentiated by the HO inhibitor, tin protoporphyrin-IX, or by the knockdown of HO-1, and reversed by the exogenous administration of biliverdin, bilirubin, or CO. These results demonstrate that HOCl induces HO-1 gene transcription via the activation of the Nrf2/ARE pathway to counteract HOCl-mediated mitochondrial dysfunction and cell death. The ability of HOCl to activate HO-1 gene expression may represent a critical adaptive response to maintain endothelial cell viability at sites of vascular inflammation and atherosclerosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine, http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Carbon Monoxide, http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1, http://linkedlifedata.com/resource/pubmed/chemical/Hypochlorous Acid, http://linkedlifedata.com/resource/pubmed/chemical/Metalloporphyrins, http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2, http://linkedlifedata.com/resource/pubmed/chemical/NFE2L2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/Protoporphyrins, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/tin protoporphyrin IX
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C907-15
pubmed:dateRevised
2011-11-4
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival.
pubmed:affiliation
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri 65212, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural