| Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells. | |
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MedLine Citation:
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PMID: 19162005 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proliferation of vascular endothelial cells (EC) and smooth muscle cells (SMC) is a critical event in angiogenesis and atherosclerosis. We previously showed that the C5b-9 assembly during complement activation induces cell cycle in human aortic EC (AEC) and SMC. C5b-9 can induce the expression of Response Gene to Complement (RGC)-32 and over expression of this gene leads to cell cycle activation. Therefore, the present study was carried out to test the requirement of endogenous RGC-32 for the cell cycle activation induced by C5b-9 by knocking-down its expression using siRNA. We identified two RGC-32 siRNAs that can markedly reduce the expression of RGC-32 mRNA in AEC. RGC-32 silencing in these cells abolished DNA synthesis induced by C5b-9 and serum growth factors, indicating the requirement of RGC-32 activity for S-phase entry. RGC-32 siRNA knockdown also significantly reduced the C5b-9 induced CDC2 activation and Akt phosphorylation. CDC2 does not play a role in G1/S transition in HeLa cells stably overexpressing RGC-32. RGC-32 was found to physically associate with Akt and was phosphorylated by Akt in vitro. Mutation of RGC-32 protein at Ser 45 and Ser 47 prevented Akt mediated phosphorylation. In addition, RGC-32 was found to regulate the release of growth factors from AEC. All these data together suggest that cell cycle induction by C5b-9 in AEC is RGC-32 dependent and this is in part through regulation of Akt and growth factor release. |
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Authors:
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Matthew Fosbrink; Cornelia Cudrici; Cosmin A Tegla; Kateryna Soloviova; Takahiro Ito; Sonia Vlaicu; Violeta Rus; Florin Niculescu; Horea Rus |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2009-01-07 |
Journal Detail:
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Title: Experimental and molecular pathology Volume: 86 ISSN: 1096-0945 ISO Abbreviation: Exp. Mol. Pathol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-02 Completed Date: 2009-04-15 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 0370711 Medline TA: Exp Mol Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 87-94 Citation Subset: IM |
Affiliation:
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Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Angiogenesis Inducing Agents / metabolism CDC2 Protein Kinase / metabolism Cell Cycle / drug effects* Cell Cycle Proteins / genetics, metabolism* Complement Membrane Attack Complex / pharmacology* Cyclin-Dependent Kinase Inhibitor p27 / metabolism Endothelial Cells / cytology*, drug effects*, enzymology Enzyme Activation / drug effects Hela Cells Humans Membrane Proteins / metabolism Muscle Proteins / genetics, metabolism* Nerve Tissue Proteins / genetics, metabolism* Nuclear Proteins / metabolism Phosphorylation / drug effects Protein Binding / drug effects Proto-Oncogene Proteins c-akt / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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ES 07263/ES/NIEHS NIH HHS; R01 NS042011-05/NS/NINDS NIH HHS; R01 NS42011/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inducing Agents; 0/CDC6 protein, human; 0/Cell Cycle Proteins; 0/Complement Membrane Attack Complex; 0/Membrane Proteins; 0/Muscle Proteins; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/PIGF protein, human; 0/RGC32 protein, human; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.22/CDC2 Protein Kinase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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