Source:http://linkedlifedata.com/resource/pubmed/id/16959872
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2006-11-28
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| pubmed:abstractText |
Macrophages play a central role in the pathogenesis of atherosclerosis by accumulating cholesterol through increased uptake of oxidized low-density lipoproteins by scavenger receptor CD36, leading to foam cell formation. Here we demonstrate the ability of hexarelin, a GH-releasing peptide, to enhance the expression of ATP-binding cassette A1 and G1 transporters and cholesterol efflux in macrophages. These effects were associated with a transcriptional activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma in response to binding of hexarelin to CD36 and GH secretagogue-receptor 1a, the receptor for ghrelin. The hormone binding domain was not required to mediate PPARgamma activation by hexarelin, and phosphorylation of PPARgamma was increased in THP-1 macrophages treated with hexarelin, suggesting that the response to hexarelin may involve PPARgamma activation function-1 activity. However, the activation of PPARgamma by hexarelin did not lead to an increase in CD36 expression, as opposed to liver X receptor (LXR)alpha, suggesting a differential regulation of PPARgamma-targeted genes in response to hexarelin. Chromatin immunoprecipitation assays showed that, in contrast to a PPARgamma agonist, the occupancy of the CD36 promoter by PPARgamma was not increased in THP-1 macrophages treated with hexarelin, whereas the LXRalpha promoter was strongly occupied by PPARgamma in the same conditions. Treatment of apolipoprotein E-null mice maintained on a lipid-rich diet with hexarelin resulted in a significant reduction in atherosclerotic lesions, concomitant with an enhanced expression of PPARgamma and LXRalpha target genes in peritoneal macrophages. The response was strongly impaired in PPARgamma(+/-) macrophages, indicating that PPARgamma was required to mediate the effect of hexarelin. These findings provide a novel mechanism by which the beneficial regulation of PPARgamma and cholesterol metabolism in macrophages could be regulated by CD36 and ghrelin receptor downstream effects.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCG1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/ATP binding cassette transporter 1,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD36,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Ghrelin,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-aminobutyryl-2-methyltryptophy...,
http://linkedlifedata.com/resource/pubmed/chemical/hexarelin,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0888-8809
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
20
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3165-78
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16959872-ATP-Binding Cassette Transporters,
pubmed-meshheading:16959872-Animals,
pubmed-meshheading:16959872-Antigens, CD36,
pubmed-meshheading:16959872-Apolipoproteins E,
pubmed-meshheading:16959872-Atherosclerosis,
pubmed-meshheading:16959872-Cells, Cultured,
pubmed-meshheading:16959872-Cholesterol,
pubmed-meshheading:16959872-DNA-Binding Proteins,
pubmed-meshheading:16959872-Humans,
pubmed-meshheading:16959872-Lipoproteins,
pubmed-meshheading:16959872-Macrophages, Peritoneal,
pubmed-meshheading:16959872-Mice,
pubmed-meshheading:16959872-Mice, Knockout,
pubmed-meshheading:16959872-Oligopeptides,
pubmed-meshheading:16959872-Orphan Nuclear Receptors,
pubmed-meshheading:16959872-PPAR gamma,
pubmed-meshheading:16959872-Phosphorylation,
pubmed-meshheading:16959872-Promoter Regions, Genetic,
pubmed-meshheading:16959872-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:16959872-Receptors, G-Protein-Coupled,
pubmed-meshheading:16959872-Receptors, Ghrelin,
pubmed-meshheading:16959872-Transcription, Genetic,
pubmed-meshheading:16959872-Up-Regulation
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| pubmed:year |
2006
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| pubmed:articleTitle |
A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway.
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| pubmed:affiliation |
Faculty of Pharmacy, Pavillon Jean-Coutu, and Research Center, Ste-Justine Hospital, University of Montreal, Montréal, Québec, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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