Fiche publication
Date publication
janvier 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel
,
Pr FAVRET Fabrice
Tous les auteurs :
Enache I, Charles AL, Bouitbir J, Favret F, Zoll J, Metzger D, Oswald-Mammosser M, Geny B, Charloux A
Lien Pubmed
Résumé
We assessed the time courses of mitochondrial biogenesis factors and respiration in the right ventricle (RV), gastrocnemius (GAS), and left ventricle (LV) in a model of pulmonary-hypertensive rats. Monocrotaline (MT) rats and controls were studied 2 and 4 weeks after injection. Compensated and decompensated heart failure stages were defined according to obvious congestion signs. mRNA expression and protein level of peroxisome proliferator activated receptor gamma co-activator 1alpha (PGC-1alpha), citrate synthase (CS) mRNA and activity, and mitochondrial respiration were investigated. In addition, mRNA expression of sirtuin1, nuclear respiratory factor 1, and mitochondrial transcription factor A were studied. As early as 2 weeks, the expression of the studied genes was decreased in the MT GAS. At 4 weeks, the MT GAS and MT RV showed decreased mRNA levels whatever the stage of disease, but PGC-1alpha protein and CS activity were significantly reduced only at the decompensated stage. The functional result was a significant fall in mitochondrial respiration at the decompensated stage in the RV and GAS. The mRNA expression and mitochondrial respiration were not significantly modified in the MT LV. MT rats demonstrated an early decrease in expression of genes involved in mitochondrial biogenesis in a skeletal muscle, whereas reduced protein expression, and the resulting mitochondrial respiratory dysfunction appeared only in rats with overt heart failure, in the GAS and RV. Dissociations between mRNA and protein levels at the compensated stage deserve to be further studied.
Référence
Mol Cell Biochem. 2013 Jan;373(1-2):161-70
