期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 40, 期 4, 页码 451-454出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2005.12.011
关键词
proteolysis; protein folding; heat shock protein; alpha B-crystallin
资金
- NHLBI NIH HHS [R01 HL072166, R01 HL-72166] Funding Source: Medline
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 (Fisp), alpha B-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. (c) 2006 Elsevier Ltd. All rights reserved.
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