Document Detail


Adriamycin depresses in vivo and in vitro phosphatidylethanolamine N-methylation in rat heart sarcolemma.
MedLine Citation:
PMID:  9406167     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adriamycin, an effective anticancer chemotherapeutic agent, causes an insidious and delayed cardiotoxicity. Different subcellular abnormalities including calcium transport changes in the sarcolemma (SL) as well as downregulation of the adrenergic system have been shown to be associated with the development of this cardiomyopathy. Since both of these activities are influenced by phospholipid methylation, effects of adriamycin on the three catalytic sites of SL phosphatidylethanolamine N-methyltransferase were examined. Rats were administered with a cumulative dose of adriamycin (15 mg/kg) over 2 weeks and examined after 3 weeks. Vehicle injected animals served as controls. Dyspnea, high mortality rate, ascites and decrease in aortic and left ventricular systolic pressure, as well as increase in left ventricular end diastolic pressure were seen in the adriamycin group. Myocardial cell damage typical of adriamycin cardiomyopathy, i.e. sarcotubular swelling, vacuolization and myofibrillar drop-out, was also apparent. Total methyl group incorporation into SL phosphatidylethanolamine using radiolabeled S-adenosyl-L-methionine as the donor was significantly depressed in the 3 week group at catalytic sites II and III. Decreased production of methylated intermediates, phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine as well as phosphatidylcholine (PC) was seen. Depression of phosphatidylethanolamine N-methylation was also noticed when SL, isolated from untreated hearts, was exposed in vitro to different concentrations (10, 100 and 1000 microM) of adriamycin. Inhibition of phosphatidylethanolamine N-methylation appears to be mediated by adriamycin-induced increase in the oxidative stress and may contribute in the pathogenesis of subcellular changes associated with this cardiomyopathy.
Authors:
N Iliskovic; V Panagia; J Slezák; D Kumar; T Li; P K Singal
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  176     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-01-23     Completed Date:  1998-01-23     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  235-40     Citation Subset:  IM    
Affiliation:
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Antineoplastic Agents / pharmacology*
Cardiomyopathies / chemically induced,  metabolism*,  physiopathology
Doxorubicin / pharmacology*
Hemodynamics / drug effects,  physiology
Male
Methylation / drug effects
Myocardium / metabolism
Phosphatidylethanolamines / chemistry,  metabolism*
Rats
Rats, Sprague-Dawley
Sarcolemma / chemistry,  drug effects*
Stroke Volume / drug effects
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Phosphatidylethanolamines; 23214-92-8/Doxorubicin

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


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