Document Detail


Nrf2-dependent and -independent responses to nitro-fatty acids in human endothelial cells: identification of heat shock response as the major pathway activated by nitro-oleic acid.
MedLine Citation:
PMID:  19808663     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Electrophilic fatty acid derivatives, including nitrolinoleic acid and nitro-oleic acid (OA-NO(2)), can mediate anti-inflammatory and pro-survival signaling reactions. The transcription factor Nrf2, activated by electrophilic fatty acids, suppresses redox-sensitive pro-inflammatory gene expression and protects against vascular endothelial oxidative injury. It was therefore postulated that activation of Nrf2 by OA-NO(2) accounts in part for its anti-inflammatory actions, motivating the characterization of Nrf2-dependent and -independent effects of OA-NO(2) on gene expression using genome-wide transcriptional profiling. Control and Nrf2-small interfering RNA-transfected human endothelial cells were treated with vehicle, oleic acid, or OA-NO(2), and differential gene expression profiles were determined. Although OA-NO(2) significantly induced the expression of Nrf2-dependent genes, including heme oxygenase-1 and glutamate-cysteine ligase modifier subunit, the majority of OA-NO(2)-regulated genes were regulated by Nrf2-independent pathways. Moreover, gene set enrichment analysis revealed that the heat shock response is the major pathway activated by OA-NO(2), with robust induction of a number of heat shock genes regulated by the heat shock transcription factor. Inasmuch as the heat shock response mediates anti-inflammatory and cytoprotective actions, this mechanism is proposed to contribute to the protective cell signaling functions of nitro-fatty acids and other electrophilic fatty acid derivatives.
Authors:
Emilia Kansanen; Henna-Kaisa Jyrkkänen; Oscar L Volger; Hanna Leinonen; Annukka M Kivelä; Sanna-Kaisa Häkkinen; Steven R Woodcock; Francisco J Schopfer; Anton J Horrevoets; Seppo Ylä-Herttuala; Bruce A Freeman; Anna-Liisa Levonen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2010-01-21     Revised Date:  2012-05-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  33233-41     Citation Subset:  IM    
Affiliation:
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, FIN-70211 Kuopio, Finland.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Line
Cells, Cultured
Cluster Analysis
Dose-Response Relationship, Drug
Endothelial Cells / cytology,  drug effects*,  metabolism
Gene Expression / drug effects
Gene Expression Profiling
Glutamate-Cysteine Ligase / genetics,  metabolism
Heme Oxygenase-1 / genetics,  metabolism
Hot Temperature
Humans
Linoleic Acids / pharmacology*
NAD(P)H Dehydrogenase (Quinone) / genetics,  metabolism
NF-E2-Related Factor 2 / genetics*,  metabolism
Nitro Compounds / pharmacology*
Oleic Acids / pharmacology*
Oligonucleotide Array Sequence Analysis
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Grant Support
ID/Acronym/Agency:
R01 HL58115/HL/NHLBI NIH HHS; R01 HL64937/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/10-nitro-9,12-octadecadienoic acid; 0/Linoleic Acids; 0/NF-E2-Related Factor 2; 0/NFE2L2 protein, human; 0/Nitro Compounds; 0/Oleic Acids; EC 1.14.99.3/HMOX1 protein, human; EC 1.14.99.3/Heme Oxygenase-1; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2/NQO1 protein, human; EC 6.3.2.2/Glutamate-Cysteine Ligase; EC 6.3.2.2/glutamate-cysteine ligase modifier subunit, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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