| Mitogen-activated protein kinase inhibitor, PD98059, inhibits rat retinal pigment epithelial cell replication by cell cycle arrest. | |
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MedLine Citation:
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PMID: 12543189 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To investigate the effect of PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, on the replication of rat cultured retinal pigment epithelial (RPE) cells. METHODS: Growth-phase rat RPE cells were exposed to various concentrations of PD98059 in serum-free F12 medium containing 0.1% dimethyl sulfoxide. Cell proliferation was assessed by cell counts using a hemocytometer. Cell viability was tested by CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay at 24 hours after PD98059 application. Hoechst 33552 and propidium iodide staining were used to assess nuclear morphology. Immunostaining with Ki67 antibody was used for cell cycle analysis because the staining patterns produced on cells are characteristic depending on their position within the cell cycle. RESULTS: PD98059 inhibited cellular proliferation of cultured rat RPE cells in a dose-dependent manner but did not induce cell death. Twenty-four hours after the application of PD98059, cultured RPE cells were not immunopositive for Ki67, indicating that their cell cycle was arrested in the G0/G1 phase. CONCLUSION: These results demonstrated that MAPK inhibition arrested cell cycle progression of rat cultured RPE cells at the G0/G1 phase. The pharmacological induction of cell cycle arrest could be a new approach to inhibit cellular proliferation in such conditions as proliferative vitreoretinopathy. |
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Authors:
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Katsuhiro Yamaguchi; Hiroshi Tomita; Eriko Sugano; Toru Nakazawa; Makoto Tamai |
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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: Japanese journal of ophthalmology Volume: 46 ISSN: 0021-5155 ISO Abbreviation: Jpn. J. Ophthalmol. Publication Date: 2002 Nov-Dec |
Date Detail:
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Created Date: 2003-01-24 Completed Date: 2003-03-27 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0044652 Medline TA: Jpn J Ophthalmol Country: United States |
Other Details:
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Languages: eng Pagination: 634-9 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzimidazoles / diagnostic use Cell Count Cell Division / drug effects Cells, Cultured DNA Replication / drug effects* Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology* Flavonoids / pharmacology* Fluorescent Dyes / diagnostic use Ki-67 Antigen / metabolism Microscopy, Fluorescence Mitogen-Activated Protein Kinases / antagonists & inhibitors* Pigment Epithelium of Eye / cytology*, metabolism Propidium / diagnostic use Rats Rats, Long-Evans |
| Chemical | |
Reg. No./Substance:
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0/Benzimidazoles; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Fluorescent Dyes; 0/Ki-67 Antigen; 0/PD 98059; 23491-52-3/HOE 33342; 36015-30-2/Propidium; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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