Document Detail


Mechanisms underlying maintenance of smooth muscle cell quiescence in rat aorta: role of the cyclin dependent kinases and their inhibitors.
MedLine Citation:
PMID:  11744034     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: We sought to understand why smooth muscle cell proliferation is effectively repressed in intact rat aortic tissue.
METHODS: Quiescent isolated rat aortic smooth muscle cells and segments of intact rat aorta were stimulated with 10% serum and the time course of expression and activity of proteins involved in cell cycle control were determined.
RESULTS: After serum stimulation, smooth muscle cells in intact aortic tissue exhibit no proliferation, whereas isolated cells entered S phase 14-16 h later. Activation of ERKs 1 and 2, and induction of cyclin D1 occurred both in isolated cells and aortic tissue. Regulation of Cdk4, cyclin E and Cdk2 protein levels was also not different. Levels of the cyclin-dependent kinase inhibitors (CKIs), p16 and p27, were initially high in quiescent isolated cells and tissue; levels were downregulated by serum in isolated cells but not in aortic tissue. Cyclin D1/Cdk4, and cyclin E/Cdk2 kinases were active before S phase entry in isolated cells, but remained inactive in aortic tissue.
CONCLUSIONS: Cell cycle entry is prevented in aortic tissue, and this is associated with an inability to downregulate p16 and p27 CKIs, and therefore to activate cyclin D1 and cyclin E associated kinase activities.
Authors:
Tanya D Izzard; Christine Taylor; Sonia D Birkett; Christopher L Jackson; Andrew C Newby
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  53     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-05-30     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  242-52     Citation Subset:  IM    
Affiliation:
Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta
Blotting, Western
CDC2-CDC28 Kinases*
Cell Division
Cells, Cultured
Cyclin D1 / metabolism
Cyclin E / metabolism
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinases / antagonists & inhibitors,  metabolism*
Enzyme Activation
Immunohistochemistry / methods
Male
Microfilament Proteins / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Muscle Proteins*
Muscle, Smooth, Vascular / cytology,  metabolism*
Organ Culture Techniques
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins*
Rats
Rats, Wistar
Thymidine / metabolism
Chemical
Reg. No./Substance:
0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Microfilament Proteins; 0/Muscle Proteins; 0/Proto-Oncogene Proteins; 0/Tagln protein, mouse; 136601-57-5/Cyclin D1; 50-89-5/Thymidine; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cdk2 protein, rat; EC 2.7.11.22/Cdk4 protein, rat; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1

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


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