Document Detail


Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization.
MedLine Citation:
PMID:  22342272     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration. Sterculic acid demonstrated to be 5-10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration.
Authors:
Jiahn-Dar Huang; Juan Amaral; Jung Wha Lee; Ignacio M Larrayoz; Ignacio R Rodriguez
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-02-08
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1821     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2013-02-04     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  637-46     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
Affiliation:
Mechanism of Retinal Diseases Section, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Choroidal Neovascularization / etiology,  pathology,  prevention & control*
Cyclopropanes / pharmacology*
Cytokines / genetics,  metabolism
Dose-Response Relationship, Drug
Drug Antagonism
Endoplasmic Reticulum Stress / drug effects,  genetics
Enzyme Inhibitors / pharmacology
Fatty Acids / pharmacology
Fatty Acids, Monounsaturated / pharmacology*
Gene Expression / drug effects
Heat-Shock Proteins / genetics,  metabolism
Humans
Immunoblotting
Inflammation / genetics,  metabolism,  prevention & control*
Inflammation Mediators / metabolism
Ketocholesterols / pharmacology*
Lasers / adverse effects
Male
Rats
Rats, Inbred BN
Retinal Pigment Epithelium / cytology,  drug effects,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor CHOP / genetics,  metabolism
Vascular Endothelial Growth Factor A / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
ZIA EY000307-17/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclopropanes; 0/Cytokines; 0/DDIT3 protein, human; 0/Enzyme Inhibitors; 0/Fatty Acids; 0/Fatty Acids, Monounsaturated; 0/Heat-Shock Proteins; 0/Inflammation Mediators; 0/Ketocholesterols; 0/Vascular Endothelial Growth Factor A; 0/molecular chaperone GRP78; 147336-12-7/Transcription Factor CHOP; MXV06G5ROK/sterculic acid; O7676FE78M/7-ketocholesterol
Comments/Corrections

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