Document Detail


Endoreduplication of human smooth muscle cells induced by 2-methoxyestradiol: a role for cyclin-dependent kinase 2.
MedLine Citation:
PMID:  17056669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endoreduplication has been suggested to contribute to the development of hypertrophy of smooth muscle cells (SMCs) in hypertension. However, endoreduplication in vascular SMCs and the underlying molecular mechanisms are not clear. Treatment of human SMCs with 10 microM 2-methoxyestradiol (2-ME) for 24 h induces accumulation of cells with > or =4N DNA content, and some polyploid/aneuploid cells actively synthesize their DNA, suggesting the occurrence of endoreduplication. In addition, 2-ME treatment upregulates the expression of cyclin-dependent kinase 2 (Cdk2). The present study was designed to characterize endoreduplication of human SMCs and explore the potential roles of Cdk2 in endoreduplication induced by 2-ME. Treatment with 2-ME (10 microM) for 2-4 days not only caused increases in >4N cells and their reentry into S phase but also induced overduplication of chromosomes. Furthermore, 2-ME increased the kinase activity of Cdk2 and its interaction with cyclin E. Inducible overexpression of dominant-negative Cdk2 in human SMCs inhibited both DNA synthesis of >4N cells and the accumulation of >4N cells induced by 2-ME. We conclude that 2-ME induces endoreduplication of human SMCs and Cdk2 plays an important role in endoreduplication in response to 2-ME.
Authors:
Yu Gui; Hao Yin; Jia-Yin He; Song-Hua Yang; Michael P Walsh; Xi-Long Zheng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-20
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  292     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-06     Completed Date:  2007-04-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1313-20     Citation Subset:  IM    
Affiliation:
Smooth Muscle Research Group, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Univ of Calgary, Calgary, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aneuploidy
Aorta
Cell Division / drug effects
Cyclin-Dependent Kinase 2 / genetics*
DNA Replication / drug effects
Estradiol / analogs & derivatives*,  pharmacology
Gene Expression Regulation, Enzymologic
Humans
Hypertension / pathology
Muscle, Smooth, Vascular / cytology*,  drug effects,  enzymology
Chemical
Reg. No./Substance:
362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; EC 2.7.11.22/Cyclin-Dependent Kinase 2

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


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