Aberrant protein aggregation is essential for a mutant desmin to impair the proteolytic function of the ubiquitin-proteasome system in cardiomyocytes

Jinbao Liu, Mingxin Tang, Ruben Mestril, Xuejun Wang

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Aberrant protein aggregates in cardiomyocytes are frequently observed in many forms of cardiomyopathies and are often associated with impairment of proteolytic function of the ubiquitin-proteasome system (UPS). However, a causal relationship between mutant desmin (MT-des) induced aberrant protein aggregation and UPS impairment has not been established. The present study has tested the causal relationship. In cultured neonatal rat ventricular myocytes, modest overexpression of a human (cardio)myopathy-linked MT-des protein led to formation of desmin-positive aggregates and inhibited UPS proteolytic function in cardiomyocytes in a dose-dependent manner. Prevention or reduction of aberrant protein aggregation by co-expression of a heat shock protein (Hsp), αB-crystallin or inducible Hsp70, or by treatment of Congo red prevented and/or significantly attenuated the induction of UPS malfunction by MT-des. These findings prove for the first time that aberrant protein aggregation is not only sufficient but also required for MT-des to impair UPS proteolytic function in cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)451-454
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume40
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Heat shock protein
  • Protein folding
  • Proteolysis
  • αB-crystallin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Aberrant protein aggregation is essential for a mutant desmin to impair the proteolytic function of the ubiquitin-proteasome system in cardiomyocytes'. Together they form a unique fingerprint.

  • Cite this