Document Detail


Cardiac-specific overexpression of E3 ligase Nrdp1 increases ischemia and reperfusion-induced cardiac injury.
MedLine Citation:
PMID:  21312039     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiomyocyte death is a major event of myocardial infarction. Previously, we and others have shown that E3 ligase-mediated protein turnover plays a critical role in cardiac injury. In this study, we sought to determine the role of a newly identified E3 ligase, neuregulin receptor degradation protein-1 (Nrdp1), on cardiac ischemia/reperfusion (I/R) injury. I/R injury markedly upregulated Nrdp1 expression in heart tissue. To elucidate the role of Nrdp1 in I/R-induced cardiac injury, neonatal cardiomyocytes were infected with adenoviral constructs expressing wild-type, dominant-negative Nrdp1 genes. Increased Nrdp1 expression enhanced I/R-induced cardiomyocyte apoptosis and inflammation as compared with the green fluorescent protein (GFP) control; these effects were attenuated by overexpression of a dominant-negative Nrdp1 (C34S/H36Q). Furthermore, cardiac-specific Nrdp1 overexpression in vivo in mouse significantly increased infarct size, the number of TUNEL-positive nuclei and inflammatory cells, as well as mortality, as compared with wild-type mice after I/R injury. The mechanisms underlying these effects were associated with the downregulation of an Nrdp1 substrate, ErbB3, accompanied by suppression of its downstream targets AKT, ERK1/2, and activation of p38 and JNK1/2. Together, these results provide evidence for an important role for Nrdp1 in regulating I/R-induced cardiac injury. Nrdp1 may constitute a new therapeutic target for ameliorating the I/R-induced cardiac injury.
Authors:
Yuan Zhang; Yong Zeng; Min Wang; Cui Tian; Xu Ma; Houzao Chen; Quan Fang; Lixin Jia; Jie Du; Huihua Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-11
Journal Detail:
Title:  Basic research in cardiology     Volume:  -     ISSN:  1435-1803     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pathology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
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