| Senescent phenotype can be reversed by reduction of caveolin status. | |
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MedLine Citation:
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PMID: 12730243 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hyporesponsiveness to growth factors is one of the fundamental characteristics of senescent cells. We previously reported that the up-regulation of caveolin attenuates the growth factor response and the subsequent downstream signal cascades in senescent human diploid fibroblasts. Therefore, in the present experiment, we investigated the modulation of caveolin status in senescent cells to determine the effect of caveolin on mitogenic signaling efficiency and cell cycling. We reduced the level of caveolin-1 in senescent human diploid fibroblasts using its antisense oligonucleotides and small interfering RNA, and this resulted in the restoration of normal growth factor responses such as the increased phosphorylation of Erk, the nuclear translocation of p-Erk, and the subsequent activation of p-Elk upon epidermal growth factor stimulation. Moreover, DNA synthesis and the re-entry of senescent cells into cell cycle were resumed upon epidermal growth factor stimulation concomitantly with decreases in p53 and p21. Taken together, we conclude that the loss of mitogenic signaling in senescent cells is strongly related to their elevated levels of caveolin-1 and that the functional recovery of senescent cells at least in the terms of growth factor responsiveness and cell cycle entry might be achieved simply by lowering the caveolin level. |
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Authors:
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Kyung A Cho; Sung Jin Ryu; Jeong Soo Park; Ik Soon Jang; Jeong Soo Ahn; Kyung Tae Kim; Sang Chul Park |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-05-01 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Jul |
Date Detail:
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Created Date: 2003-07-21 Completed Date: 2003-08-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 27789-95 Citation Subset: IM |
Affiliation:
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The Aging and Apoptosis Research Center, Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Caveolin 1 Caveolins / metabolism* Cell Aging* Cell Cycle Cell Division Cells, Cultured DNA / biosynthesis, metabolism Down-Regulation Epidermal Growth Factor / metabolism Fibroblasts / metabolism Humans Immunohistochemistry Microscopy, Electron Microscopy, Fluorescence Mitogen-Activated Protein Kinases / metabolism Oligonucleotides, Antisense / metabolism Phenotype Proto-Oncogene Proteins p21(ras) / metabolism RNA, Small Interfering / metabolism Signal Transduction Subcellular Fractions / metabolism Time Factors Transfection Tumor Suppressor Protein p53 / metabolism Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/CAV1 protein, human; 0/Caveolin 1; 0/Caveolins; 0/Oligonucleotides, Antisense; 0/RNA, Small Interfering; 0/Tumor Suppressor Protein p53; 62229-50-9/Epidermal Growth Factor; 9007-49-2/DNA; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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