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PMID: 8895103 Published · ppublish English Journal Article

Effects of fluoro-doxorubicin (ME2303) on microtubules: influence of different classes of microtubule-associated proteins.

Journal of protein chemistry ·Vol. 15 ·No. 6 ·1996-08-00 ·Pages 561-73

Fromes Y, Gounon P, Tapiero H, Fellous A

Abstract

Anthracyclines are among the most useful agents for the treatment of neoplastic disease, but their clinical use is limited by progressive cardiomyopathy. A few studies have suggested the role of microtubules for the understanding of this toxicity. By using kinetic and structural studies, we demonstrate the disorganizing action of fluoro-doxorubicin, a novel anthracycline, on the microtubule system. Microtubules have a rich and complex composition in relation to their numerous functions in cells. In the present study, we investigate the role of two major microtubule-associated protein (MAP) families, Tau and MAP2. Both MAP families are responsible for the properties of different classes of microtubules. We show the differential effect of fluoro-doxorubicin on these two classes of microtubules. Furthermore, we show that fluoro-doxorubicin is able to affect the capacity of purified tubulin to form normal microtubules. This study confirms that anthracyclines may interfer with the microtubule organization. We suggest that some classes of microtubules, with regard to their MAP composition, may be affected more specifically in cardiac myocytes.

MeSH Terms
Animals Brain/drug effects,metabolism Doxorubicin/analogs & derivatives,pharmacology Microscopy, Electron Microtubule-Associated Proteins/metabolism Microtubules/drug effects,ultrastructure Rats
Chemicals
Microtubule-Associated Proteins ME 2303 Doxorubicin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fromes Y
Institut de Génétique Moléculaire, Laboratorie de Pharmacologie Expérimentale 27, Paris, France.
Gounon P
Tapiero H
Fellous A
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Article Info
Journal
Journal of protein chemistry
Abbr.
J Protein Chem
ISSN
0277-8033
DOI
10.1007/BF01908538
Published
1996-08-00
Pages
561-73
Language
English
Region
United States
NLM ID
8217321
Subset
IM
External Links
PubMed source DOI: 10.1007/BF01908538
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