| Unoprostone isopropyl rescues retinal progenitor cells from apoptosis in vitro. | |
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MedLine Citation:
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PMID: 15764090 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Unoprostone isopropyl is an ocular hypotensive that was originally produced as a prostaglandin F2alpha analogue and is eventually recognized as a synthetic docosanoid. The compound is recently suggested to have potent neuroprotective ability in the retina. The purpose of this study is to test whether and how the biologically active metabolites of unoprostone isopropyl rescue retinal neuro-glial progenitor cells from apoptosis. METHODS: R28 cells were deprived of serum for 24 hr with or without varying concentrations of unoprostone metabolite M1 or M2 or vehicle in the presence or absence of specific inhibitors against several types of signal transduction proteins. Immunocytochemistry against activated caspase-3 with Hoechst nuclear staining was performed. RESULTS: Up to 15%of R28 cells became pyknotic and activated caspase-3 immunoreactive after 24-hr serum withdrawal. M1, but not M2, significantly reduced apoptotic cells in a dose-dependent fashion with a maximal effect at 100 microM (p < .0001). LY294002, the phosphatidylinositol 3-OH kinase (PI3K) inhibitor, and KT5823, the protein kinase G (PKG) inhibitor, reversed the antiapoptotic effect of M1. CONCLUSIONS: The unoprostone metabolite M1 protects retinal neuro-glial progenitor R28 cells from apoptosis induced by serum deprivation via the PI3K and PKG pathways. |
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Authors:
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Hirokazu Mukuno; Makoto Nakamura; Akiyasu Kanamori; Azusa Nagai; Akira Negi; Gail Seigel |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Current eye research Volume: 29 ISSN: 0271-3683 ISO Abbreviation: Curr. Eye Res. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2005-03-14 Completed Date: 2005-03-24 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8104312 Medline TA: Curr Eye Res Country: England |
Other Details:
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Languages: eng Pagination: 457-64 Citation Subset: IM |
Affiliation:
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Department of Organ Therapeutics, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-Ku, Kobe, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors,
metabolism Animals Apoptosis / drug effects* Carbazoles / pharmacology Caspase 3 Caspases / metabolism Chromones / pharmacology Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors, metabolism Cytoprotection / drug effects Dinoprost / analogs & derivatives*, pharmacology* Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Fluorescent Antibody Technique, Indirect Indoles / pharmacology Morpholines / pharmacology Rats Retina / cytology*, enzymology Stem Cells / cytology*, enzymology |
| Chemical | |
Reg. No./Substance:
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0/Carbazoles; 0/Chromones; 0/Enzyme Inhibitors; 0/Indoles; 0/Morpholines; 126643-37-6/KT 5823; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 551-11-1/Dinoprost; 69553-75-9/isopropyl unoprostone; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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