Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site

Autor: Francis Bayard, Jean-François Arnal, Kazuhito Rokutan, Kazumi Kondo, Irma Gabriela Gonzalez-Herrera, Anne-Catherine Prats, Shigetada Teshima-Kondo, Leonel Prado-Lourenco
Přispěvatelé: Blanquart, Nicole, Department of Stress Science, Institute of Health Biosciences-Tokushima University, MilleGen, Prologue Biotech, Hormones, facteurs de croissance et physiopathologie vasculaire, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Genetically modified mouse
Biology
Fibroblast growth factor
Biochemistry
Substrate Specificity
Mice
Translational regulation
Genetics
Protein biosynthesis
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
MESH: Up-Regulation
Animals
Luciferase
MESH: Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
RNA
Messenger
Molecular Biology
MESH: Mice
Aorta
MESH: Organ Specificity
MESH: RNA
Messenger
Messenger RNA
Binding Sites
MESH: Fibroblast Growth Factor 2
fungi
Translation (biology)
MESH: Aorta
Molecular biology
Up-Regulation
MESH: Glucose
Internal ribosome entry site
Glucose
MESH: Binding Sites
Organ Specificity
Hyperglycemia
Protein Biosynthesis
MESH: Protein Biosynthesis
Fibroblast Growth Factor 2
MESH: Substrate Specificity
MESH: Hyperglycemia
Ribosomes
MESH: Ribosomes
Biotechnology
Zdroj: FASEB Journal
FASEB Journal, 2004, 18 (13), pp.1583-5. ⟨10.1096/fj.03-1118fje⟩
ISSN: 0892-6638
1530-6860
Popis: 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.
Databáze: OpenAIRE
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