Linked Life Data

15544924

Source:http://linkedlifedata.com/resource/pubmed/id/15544924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-11-16
pubmed:abstractText
Cholesterol-independent, pleiotropic actions of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert anti-inflammatory and antioxidant action by as yet unidentified mechanisms. This study explores the role of heme oxygenase 1 (HO-1) as a target and mediator of statins. In cultured endothelial cells derived from human umbilical vein, simvastatin and lovastatin increased HO-1 mRNA levels in a concentration- and time-dependent fashion. HO-1 induction by statins remained unaffected by mevalonate and N-nitro-l-arginine methyl ester, precluding the involvement of isoprenoid- and NO-dependent pathways. HO-1 mRNA induction was abrogated in the presence of actinomycin D and cycloheximide. In cells transfected with a reporter gene construct containing the proximal 4 kB of the HO-1 gene promoter 5'-flanking region, significant upregulation of promoter activity was detected, indicating that regulatory elements binding to this region were involved in transcriptional HO-1 induction by statins. Increased transcriptional expression of HO-1 was associated with elevated HO-1 protein levels and reduction of free radical formation. Our results show that the antioxidant defense protein HO-1 is a target site of statins in endothelial cells. Statins lead to HO-1 promoter activation, transcript and protein accumulation. This novel pathway may contribute to and explain the pleiotropic antioxidant, anti-inflammatory, and antiatherogenic actions of statins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2064-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells.
pubmed:affiliation
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, 06099 Halle (Saale), Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't