Document Detail

Doxorubicin and C-13 deoxydoxorubicin effects on ryanodine receptor gene expression.
MedLine Citation:
PMID:  11855807     Owner:  NLM     Status:  MEDLINE    
Chronic anthracycline administration to rabbits causes impairment of cardiac contractility and decreased gene expression of the calcium-induced calcium release channel of sarcoplasmic reticulum (SR), the ryanodine receptor (RYR2). The C-13 hydroxy metabolite (doxorubicinol), formed in the heart, has been hypothesized to contribute to anthracycline cardiotoxicity. C-13 deoxydoxorubicin is an analog unable to form the C-13 hydroxy metabolite. Therefore, doxorubicin, C-13 deoxydoxorubicin, or saline was administered to rabbits (1 mg/kg iv twice weekly for 8 weeks). Left ventricular fractional shortening (LVFS) was decreased by chronic treatment with doxorubicin (28 +/- 2%; P < 0.05), but not C-13 deoxydoxorubicin (33 +/- 2%) compared to age-matched pair-fed controls. Doxorubicin, but not C-13 deoxydoxorubicin, caused a significant reduction (P < 0.02) in the ratio of RYR2/Ca-Mg ATPase (SERCA2) mRNA levels (0.57 +/- 0.1 vs 1.22 +/- 0.2, respectively) in the left ventricle. This suggests that doxorubicinol may contribute to the downregulation of cardiac RYR2 expression in chronic doxorubicin cardiotoxicity.
Herve A Gambliel; Briant E Burke; Barry J Cusack; Gerald M Walsh; Yumei L Zhang; Philip S Mushlin; Richard D Olson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  291     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-02-21     Completed Date:  2002-04-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  433-8     Citation Subset:  IM    
Department of Research and Development, Department of Veteran's Affairs Medical Center, Boise, Idaho 83702, USA.
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MeSH Terms
Antibiotics, Antineoplastic / chemistry,  pharmacology*
Calcium-Transporting ATPases / genetics,  metabolism
Doxorubicin / analogs & derivatives,  chemistry,  pharmacology*
Myocardial Contraction
RNA, Messenger / biosynthesis
Ryanodine Receptor Calcium Release Channel / genetics,  metabolism*
Sarcoplasmic Reticulum / metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Ventricular Dysfunction, Left / chemically induced,  genetics,  metabolism*,  physiopathology
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/C-13 deoxydoxorubicin; 0/RNA, Messenger; 0/Ryanodine Receptor Calcium Release Channel; 23214-92-8/Doxorubicin; EC ATPases; EC Reticulum Calcium-Transporting ATPases

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