Linked Life Data

18463320

Source:http://linkedlifedata.com/resource/pubmed/id/18463320

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-7-21
pubmed:abstractText
We previously reported that apolipoprotein (Apo) E-deficient, ApoB48-containing (E(-)/B48) lipoproteins inhibited expression of lysosomal hydrolase and transformed mouse peritoneal macrophages (MPMs) into foam cells. The present study examined the effect of 2-aminopurine (2-AP), an inhibitor of eukaryotic initiation factor (eIF)-2alpha phosphorylation, on E(-)/B48 lipoprotein-induced changes in gene expression and foam cell formation. Our data demonstrated that E(-)/B48 lipoproteins enhanced phosphorylation of eIF-2alpha in macrophages. Incubation of MPMs with E(-)/B48 lipoproteins inhibited the translation efficiency of mRNAs encoding lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor, with a parallel reduction in the level of these proteins. Addition of 2-AP to the culture media alleviated the suppressive effect of E(-)/B48 lipoproteins on lysosomal hydrolase mRNA translation, increased macrophage degradation of E(-)/B48 lipoproteins, and inhibited foam cell formation. Transfection of MPMs with a nonphosphorylatable eIF-2alpha mutant also attenuated the suppressive effect of E(-)/B48 lipoproteins on expression of lysosomal acid lipase, associated with a reduced accumulation of cellular cholesterol esters. This is the first demonstration that ApoE-deficient lipoproteins inhibit lysosomal hydrolase synthesis and transform macrophages into foam cells through induction of eIF-2alpha phosphorylation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
326
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
395-405
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
2-Aminopurine inhibits lipid accumulation induced by apolipoprotein E-deficient lipoprotein in macrophages: potential role of eukaryotic initiation factor-2alpha phosphorylation in foam cell formation.
pubmed:affiliation
Department of Cardiovascular Biology, Meharry Medical College, Nashville, TN 37208, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural