Document Detail


Over-expression of heat shock protein 27 attenuates doxorubicin-induced cardiac dysfunction in mice.
MedLine Citation:
PMID:  17481944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Oxidative stress and myocyte apoptosis are thought to play an important role in the pathogenesis, progression and prognosis of heart failure (HF). Heat shock protein 27 (Hsp27) has been found to confer resistance to oxidative stress in cultured cells; however, the role of Hsp27 in in-vivo hearts remains to be determined.
AIM: To investigate the effects of Hsp27 over-expression on doxorubicin-induced HF.
METHODS AND RESULTS: Transgenic mice (TG) with cardiac specific over-expression of Hsp27 and their wild type littermates (WT) were challenged with doxorubicin (25 mg/kg, IP) to induce HF. At day 5, TG mice had significantly improved cardiac function and viability and decreased loss of heart weight following doxorubicin exposure compared with WT. In another parallel experiment, doxorubicin-induced increased levels of reactive oxygen species, protein carbonylation, apoptosis and morphologic changes were detected in the mitochondria in WT hearts, whereas these effects were markedly attenuated in TG hearts. In addition, upregulation of heat shock protein 70 and heme oxygenase-1 was present in the TG hearts after doxorubicin stimulation in comparison to WT hearts.
CONCLUSION: These findings indicate that Hsp27 may play a key role in resistance to doxorubicin-induced cardiac dysfunction.
Authors:
Li Liu; Xiaojin Zhang; Bo Qian; Xiaoyan Min; Xiang Gao; Chuanfu Li; Yunlin Cheng; Jun Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-04
Journal Detail:
Title:  European journal of heart failure     Volume:  9     ISSN:  1388-9842     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-13     Completed Date:  2007-11-27     Revised Date:  2011-06-08    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  762-9     Citation Subset:  IM    
Affiliation:
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / adverse effects
Apoptosis / physiology
Blotting, Western
Disease Models, Animal
Doxorubicin / adverse effects
HSP27 Heat-Shock Proteins
Heart Failure / chemically induced,  metabolism,  physiopathology*
Heat-Shock Proteins / metabolism*
Immunohistochemistry
In Situ Nick-End Labeling
Mice
Mice, Transgenic
Mitochondria, Heart / metabolism*
Myocytes, Cardiac / ultrastructure
Organ Size / drug effects
Oxidative Stress / drug effects
Reactive Oxygen Species / analysis
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Hspb2 protein, mouse; 0/Reactive Oxygen Species; 23214-92-8/Doxorubicin

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