Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-5-1
pubmed:abstractText
The accumulation of apolipoprotein B100 lipoproteins in Bruch membrane is an early event thought to promote age-related macular degeneration (AMD). Immunohistochemistry using an anti-oxidized low density lipoprotein antibody on 10 AMD specimens showed staining in Bruch membrane including basal deposits, a marker of AMD. To determine whether retinal pigmented epithelial cells develop a pathologic phenotype after interaction with lipoproteins, ARPE-19 cells were exposed to low density lipoproteins (LDL) or oxidized LDLs (oxLDL). Analysis using the Affymetrix U133 Plus 2.0 (Affymetrix, Inc., Santa Clara, CA, USA) gene chip showed physiological and pathological transcriptional responses after LDL and oxLDL treatment, respectively. LDL induced a down-regulation of cholesterol biosynthesis genes while oxLDL induced transcriptional alterations in genes related to lipid metabolism, oxidative stress, inflammation and apoptosis. Electrospray mass spectrometry showed that oxLDL, but not LDL induced large cellular increases of sphingomyelin, ceramides, and cholesteryl esters. With TUNEL labeling, oxLDL caused 14.6% apoptosis compared to <1% after LDL. Addition of an inhibitor of sphingomyelin synthase inhibited this apoptosis by 41%. These data support the hypothesis that oxidized lipoproteins are one trigger for initiating early events in the pathogenesis of AMD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1187-97
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Oxidized low density lipoproteins induce a pathologic response by retinal pigmented epithelial cells.
pubmed:affiliation
Wilmer Eye Institute, Johns Hopkins Medical Institutes, Baltimore, Maryland 21287, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural