title: Proteomic remodeling of proteasome in right heart failure.
abstract: The development of right heart failure (RHF) is characterized by alterations of right ventricle (RV) structure and function, but the mechanisms of RHF remain still unknown. Thus, understanding the RHF is essential for improved therapies. Therefore, identification by quantitative proteomics of targets specific to RHF may have therapeutic benefits to identify novel potential therapeutic targets. The objective of this study was to analyze the molecular mechanisms changing RV function in the diseased RHF and thus, to identify novel potential therapeutic targets. For this, we have performed differential proteomic analysis of whole RV proteins using two experimental rat models of RHF. Differential protein expression was observed for hundred twenty six RV proteins including proteins involved in structural constituent of cytoskeleton, motor activity, structural molecule activity, cytoskeleton protein binding and microtubule binding. Interestingly, further analysis of down-regulated proteins, reveals that both protein and gene expressions of proteasome subunits were drastically decreased in RHF, which was accompanied by an increase of ubiquitinated proteins. Interestingly, the proteasomal activities chymotrypsin and caspase-like were decreased whereas trypsin-like activity was maintained. In conclusion, this study revealed the involvement of ubiquitin-proteasome system (UPS) in RHF. Three deregulated mechanisms were discovered: (1) decreased gene and protein expressions of proteasome subunits, (2) decreased specific activity of proteasome; and (3) a specific accumulation of ubiquitinated proteins. This modulation of UPS of RV may provide a novel therapeutic avenue for restoration of cardiac function in the diseased RHF.
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France; INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France. Electronic address: delphine.fessart@yahoo.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Fessart
authors.affiliation: Université Victor Segalen-Bordeaux 2, Centre National de la Recherche Scientifique, Institute of Neurodegenerative Diseases, 33076 Bordeaux, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Martin-Negrier
authors.affiliation: Université de Bordeaux, Centre Génomique Fonctionnelle de Bordeaux, Plateforme Protéome, F-33000 Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Claverol
authors.affiliation: Université Victor Segalen-Bordeaux 2, Centre National de la Recherche Scientifique, Institute of Neurodegenerative Diseases, 33076 Bordeaux, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Thiolat
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France; INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.
authors.forename: Huguette
authors.initials: H
authors.lastname: Crevel
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Toussaint
authors.affiliation: Université de Bordeaux, Centre Génomique Fonctionnelle de Bordeaux, Plateforme Protéome, F-33000 Bordeaux, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneu
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France; INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France; INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France; INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France. Electronic address: frederic.delom@yahoo.fr.
authors.forename: Frederic
authors.initials: F
authors.lastname: Delom
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D054875:Ubiquitination; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D020543:Proteome; D016686:Monocrotaline; D046988:Proteasome Endopeptidase Complex
keywords: Proteasomal activities; Proteasome; Quantitative proteomic; Right heart failure; Ubiquitin