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 language | English (US) |
---|---|
Pages (from-to) | 451-454 |
Number of pages | 4 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 40 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2006 |
Externally published | Yes |
Keywords
- Heat shock protein
- Protein folding
- Proteolysis
- αB-crystallin
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine