| Apolipoprotein B100 secretion by cultured ARPE-19 cells is modulated by alteration of cholesterol levels. | |
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MedLine Citation:
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PMID: 20598021 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholesteryl ester rich apolipoprotein B100 (apoB100) lipoproteins accumulate in Bruch's membrane before the development of age-related macular degeneration. It is not known if these lipoproteins come from the circulation or local ocular tissue. Emerging, but incomplete evidence suggests that the retinal pigmented epithelium (RPE) can secrete lipoproteins. The purpose of this investigation was to determine (i) whether human RPE cells synthesize and secrete apoB100, and (ii) whether this secretion is driven by cellular cholesterol, and if so, (iii) whether statins inhibit this response. The established, human derived ARPE-19 cells challenged with 0-0.8 mM oleic acid accumulated cellular cholesterol, but not triglycerides. Oleic acid increased the amount of apoB100 protein recovered from the medium by both western blot analysis and (35) S-radiolabeled immunoprecipitation while negative stain electron microscopy showed lipoprotein-like particles. Of nine statins evaluated, lipophilic statins induced HMG-CoA reductase mRNA expression the most. The lipophilic Cerivastatin (5 μM) reduced cellular cholesterol by 39% and abrogated apoB100 secretion by 3-fold. In contrast, the hydrophilic statin Pravastatin had minimal effect on apoB100 secretion. These data suggest that ARPE-19 cells synthesize and secrete apoB100 lipoproteins, that this secretion is driven by cellular cholesterol, and that statins can inhibit apoB100 secretion by reducing cellular cholesterol. |
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Authors:
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Tinghuai Wu; Masashi Fujihara; Jane Tian; Miroslava Jovanovic; Celene Grayson; Marisol Cano; Peter Gehlbach; Philippe Margaron; James T Handa |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-27 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 114 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-24 Completed Date: 2010-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 1734-44 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry. |
Affiliation:
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Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antioxidants
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pharmacology Apolipoprotein B-100 / secretion* Cell Line Cell Survival / drug effects Cholesterol / metabolism* Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Oleic Acid / pharmacology Pyridines / pharmacology Triglycerides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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EY14005/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Apolipoprotein B-100; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyridines; 0/Triglycerides; 0/cerivastatin; 112-80-1/Oleic Acid; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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