| Doxorubicin and C-13 deoxydoxorubicin effects on ryanodine receptor gene expression. | |
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MedLine Citation:
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PMID: 11855807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 291 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2002 Mar |
Date Detail:
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Created Date: 2002-02-21 Completed Date: 2002-04-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 433-8 Citation Subset: IM |
Affiliation:
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Department of Research and Development, Department of Veteran's Affairs Medical Center, Boise, Idaho 83702, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / chemistry, pharmacology* Calcium-Transporting ATPases / genetics, metabolism Down-Regulation Doxorubicin / analogs & derivatives, chemistry, pharmacology* Male Myocardial Contraction RNA, Messenger / biosynthesis Rabbits Ryanodine Receptor Calcium Release Channel / genetics, metabolism* Sarcoplasmic Reticulum / metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases Ventricular Dysfunction, Left / chemically induced, genetics, metabolism*, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/C-13 deoxydoxorubicin; 0/RNA, Messenger; 0/Ryanodine Receptor Calcium Release Channel; 23214-92-8/Doxorubicin; EC 3.6.1.8/Calcium-Transporting ATPases; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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