Skip to Main content Skip to Navigation
Journal articles

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.
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00903386
Contributor : Delphine Fessart <>
Submitted on : Tuesday, November 12, 2013 - 10:16:24 AM
Last modification on : Thursday, January 11, 2018 - 6:25:41 AM
Long-term archiving on: : Thursday, February 13, 2014 - 4:25:13 AM

Files

Identifiers

Collections

Citation

Delphine Fessart, Marie-Laure Martin-Negrier, Stéphane Claverol, Marie-Laure Thiolat, Huguette Crevel, et al.. Proteomic remodeling of proteasome in right heart failure.. Journal of Molecular and Cellular Cardiology, Elsevier, 2014, 66, pp.41-52. ⟨10.1016/j.yjmcc.2013.10.015⟩. ⟨inserm-00903386⟩

Share

Metrics

Record views

503

Files downloads

953