| Mechanisms underlying maintenance of smooth muscle cell quiescence in rat aorta: role of the cyclin dependent kinases and their inhibitors. | |
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MedLine Citation:
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PMID: 11744034 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tanya D Izzard; Christine Taylor; Sonia D Birkett; Christopher L Jackson; Andrew C Newby |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cardiovascular research Volume: 53 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2002 Jan |
Date Detail:
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Created Date: 2001-12-17 Completed Date: 2002-05-30 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 242-52 Citation Subset: IM |
Affiliation:
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Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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