Document Detail


Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells.
MedLine Citation:
PMID:  20849813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prolyl hydroxylases (PHDs) are dioxygenases that use oxygen as a co-substrate to hydroxylate proline residues. Three PHD isoforms (PHD1, PHD2 and PHD3) have been identified in mammalian cells. PHD3 expression is upregulated in some cardiac diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury and congestive heart failure, all of which are associated with apoptosis. However, the role of PHDs in cardiomyocyte apoptosis remains unknown. Here, we have found that exposure of embryonic rat heart-derived H9c2 cells to doxorubicin (DOX) induced cell apoptosis as evaluated by caspase-3/7 activity, mitochondrial membrane potential (Δψm) and cell viability, and that this apoptosis was linked to PHD3 upregulation. PHD inhibition or PHD3 silencing substantially ameliorated DOX-induced apoptosis, but PHD1 or PHD2 knockdown did not significantly influence apoptosis. Furthermore, immunoprecipitation experiments showed that PHD3 upregulation reduced the formation of the Bax-Bcl-2 complex, inhibiting the anti-apoptotic effect of Bcl-2. Thus, PHD3 upregulation may be partially responsible for DOX-induced cardiomyocyte apoptosis via its interaction with Bcl-2. Inhibition of PHD3 is likely to be cardioprotective against apoptosis in some heart disorders.
Authors:
Ying Liu; Zhaoxia Huo; Biao Yan; Xiaoping Lin; Zhao-Nian Zhou; Xingqun Liang; Weidong Zhu; Dandan Liang; Li Li; Yi Liu; Hong Zhao; Yunfu Sun; Yi-Han Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-16
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  401     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  231-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, 200120 Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Cell Line
Doxorubicin / pharmacology
Humans
Myocytes, Cardiac / drug effects,  metabolism,  physiology*
Procollagen-Proline Dioxygenase / metabolism*
Protein Structure, Tertiary
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
Rats
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 23214-92-8/Doxorubicin; EC 1.14.11.2/Procollagen-Proline Dioxygenase; EC 1.14.11.7/proline, 2-oxoglutarate 3-dioxygenase

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