Source:http://linkedlifedata.com/resource/pubmed/id/15289445
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
2004-10-6
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pubmed:abstractText |
Fibroblast growth factor 2 (FGF-2) is normally synthesized at low levels but is elevated in various pathophysiological conditions including diabetes-associated vascular diseases. FGF-2 expression is regulated translationally through an internal ribosome entry site (IRES) located in its mRNA, which allows a nonclassical cap-independent translation. We addressed the pathophysiological regulation of the IRES in vivo by using a streptozotocin-induced hyperglycemic model known to suppress markedly overall translation. Evaluation of FGF-2 IRES-dependent translation was performed with transgenic mice expressing dual luciferase bicistronic mRNA containing the FGF-2 IRES. FGF-2 IRES-dependent reporter activity increased 240% of control in the diabetic aorta although the reporter mRNA levels significantly decreased. Expression of endogenous FGF-2 protein in the aorta closely correlated with the IRES activity but not with FGF-2 mRNA levels. Moreover, the biosynthesis of endogenous FGF-2 protein was stimulated in an IRES-dependent manner by high glucose that significantly suppressed global protein synthesis in aortic smooth muscle cells from the transgenic mice. These results suggest that IRES-dependent translational regulation could play a pathological role in FGF-2 expression in vivo, especially in the cardiovascular consequences of diabetes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1530-6860
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1583-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15289445-Animals,
pubmed-meshheading:15289445-Aorta,
pubmed-meshheading:15289445-Binding Sites,
pubmed-meshheading:15289445-Fibroblast Growth Factor 2,
pubmed-meshheading:15289445-Glucose,
pubmed-meshheading:15289445-Hyperglycemia,
pubmed-meshheading:15289445-Mice,
pubmed-meshheading:15289445-Organ Specificity,
pubmed-meshheading:15289445-Protein Biosynthesis,
pubmed-meshheading:15289445-RNA, Messenger,
pubmed-meshheading:15289445-Ribosomes,
pubmed-meshheading:15289445-Substrate Specificity,
pubmed-meshheading:15289445-Up-Regulation
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pubmed:year |
2004
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pubmed:articleTitle |
Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site.
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pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale U589, Hormones, Facteurs de Croissance et Physiopathologie Vasculaire, Institut Louis Bugnard IFR31, Hôpital Rangueil, Toulouse, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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