| Cardiac-specific overexpression of E3 ligase Nrdp1 increases ischemia and reperfusion-induced cardiac injury. | |
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MedLine Citation:
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PMID: 21312039 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-2-11 |
Journal Detail:
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Title: Basic research in cardiology Volume: - ISSN: 1435-1803 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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