Document Detail


Cardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: role of ER stress.
MedLine Citation:
PMID:  20937379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paraquat, a quaternary nitrogen herbicide, is a highly toxic pro-oxidant that causes multiorgan failure including that of the heart via generation of reactive oxygen species, although the underlying mechanism has not been well elucidated. This study examined the influence of cardiac-specific overexpression of catalase, an antioxidant detoxifying H(2)O(2), on paraquat-induced myocardial geometric and functional alterations, with a focus on ER stress. FVB and catalase transgenic mice were administered paraquat for 48h. Myocardial geometry, contractile function, apoptosis, and ER stress were evaluated using echocardiography, edge detection, caspase-3 activity, and immunoblotting. Our results revealed that paraquat treatment significantly enlarged left ventricular (LV) end diastolic and systolic diameters; increased LV mass and resting myocyte length; reduced fractional shortening, cardiomyocyte peak shortening, and maximal velocity of shortening/relengthening; and prolonged relengthening duration in the FVB group. Whereas the catalase transgene itself did not alter myocardial geometry and function, it mitigated or significantly attenuated paraquat-elicited myocardial geometric and functional changes. Paraquat promoted overt apoptosis and ER stress as evidenced by increased caspase-3 activity, apoptosis, and ER stress markers including Bax, Bcl-2, GADD153, calregulin, and phosphorylated JNK, IRE1α, and eIF2α; all were ablated by the catalase transgene. Paraquat-induced cardiomyocyte dysfunction was mitigated by the ER stress inhibitor tauroursodeoxycholic acid. Moreover, the JNK inhibitor SP600125 reversed paraquat-induced ER stress as evidenced by enhanced GADD153 and IRE1α phosphorylation. Taken together, these data revealed that catalase may rescue paraquat-induced myocardial geometric and functional alteration possibly by alleviating JNK-mediated ER stress.
Authors:
Wei Ge; We Ge; Yingmei Zhang; Xuefeng Han; Jun Ren
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-27
Journal Detail:
Title:  Free radical biology & medicine     Volume:  49     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-08-18     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2068-77     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthracenes / pharmacology
Apoptosis / drug effects
Calreticulin / metabolism
Caspase 3 / metabolism
Catalase / biosynthesis,  genetics*
DNA-Binding Proteins / metabolism
Echocardiography
Endoplasmic Reticulum / physiology*
Endoribonucleases / metabolism
Enzyme Assays
Herbicides / toxicity*
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Male
Mice
Mice, Transgenic
Myocardial Contraction / drug effects*
Myocardium / enzymology*
Myocytes, Cardiac / drug effects*,  enzymology
Paraquat / toxicity*
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism
Taurochenodeoxycholic Acid / pharmacology
Transcription Factor CHOP / metabolism
Transcription Factors / metabolism
Up-Regulation / drug effects
Grant Support
ID/Acronym/Agency:
1R01 AA013412/AA/NIAAA NIH HHS; 5P20 RR016474/RR/NCRR NIH HHS; P20 RR016474/RR/NCRR NIH HHS; P20 RR016474-08/RR/NCRR NIH HHS; R01 AA013412/AA/NIAAA NIH HHS; R01 AA013412-04/AA/NIAAA NIH HHS; R01 AA013412-05/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Anthracenes; 0/Calreticulin; 0/DNA-Binding Proteins; 0/Ddit3 protein, mouse; 0/Elf2 protein, mouse; 0/Herbicides; 0/Transcription Factors; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 147336-12-7/Transcription Factor CHOP; 516-35-8/Taurochenodeoxycholic Acid; 60EUX8MN5X/tauroursodeoxycholic acid; EC 1.11.1.6/Catalase; EC 2.7.11.1/Ern1 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.1.-/Endoribonucleases; EC 3.4.22.-/Caspase 3; PLG39H7695/Paraquat
Comments/Corrections
Erratum In:
Free Radic Biol Med. 2011 Jan 1;50(1):217
Note: Ge, We [corrected to Ge, Wei]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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