| Modulation of cholesterol homeostasis by antiproliferative drugs in human pterygium fibroblasts. | |
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MedLine Citation:
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PMID: 17652712 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The authors have previously shown that the growth of cultured fibroblasts obtained from primary pterygia was associated with an increase in cholesterol esterification, suggesting that alterations of cholesterol homeostasis may be involved in the development and progression of this disorder. This investigation was conducted to determine whether antiproliferative agents such as pioglitazone (PIO) and everolimus (EVE) may inhibit proteins involved in the cholesterol ester cycle and the proliferation of pterygium fibroblasts (PF). METHODS: Quiescent normal conjunctival fibroblasts and PFs were treated with or without inhibitors of cell proliferation (PIO and EVE) or with inhibitors of cholesterol esterification-progesterone (Pg) and Sandoz compound (SaH)-and then were stimulated to growth by 10% fetal calf serum (FCS). Cell proliferation was assessed by counting cells. Trypan blue uptake was used to determine cell viability. mRNA and protein levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. RESULTS: PIO and EVE significantly abolished the increase in cholesterol esters, acyl-coenzyme A cholesterol acyltransferase (ACAT1), and multidrug resistance protein (MDR1) mRNA observed in growing cells. Each inhibitor upregulated ATP-binding cassette-A1 (ABCA1), neutral cholesterol ester hydrolase (NCEH) mRNA, and caveolin-1 expression in a manner similar to that of specific inhibitors of cholesterol esterification such as Pg and SaH. CONCLUSIONS: Intracellular modifications of cholesterol homeostasis may be relevant to pterygium development. Moreover, antiproliferative agents such as PIO and EVE may represent a potential topical medication in the prevention and inhibition of pterygium growth at an early stage, probably by modulation of cholesterol ester metabolism. |
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Authors:
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Enrico Peiretti; Sandra Dessì; Claudia Mulas; Claudia Abete; Claudia Norfo; Marirosa Putzolu; Maurizio Fossarello |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 48 ISSN: 0146-0404 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-07-26 Completed Date: 2007-09-26 Revised Date: 2009-07-23 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 3450-8 Citation Subset: IM |
Affiliation:
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Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Amides / pharmacology Caveolin 1 / metabolism Cell Division / drug effects, physiology Cells, Cultured Cholesterol / metabolism* Cholesterol Esters / metabolism Enzyme Inhibitors / pharmacology Female Fibroblasts / drug effects*, metabolism, pathology Homeostasis / drug effects, physiology Humans Hypoglycemic Agents / pharmacology* Immunosuppressive Agents / pharmacology Male Middle Aged Organosilicon Compounds / pharmacology P-Glycoprotein / genetics, metabolism Progesterone / pharmacology Pterygium / metabolism, pathology, prevention & control* RNA, Messenger / metabolism Sirolimus / analogs & derivatives, pharmacology Sterol O-Acyltransferase / genetics, metabolism Thiazolidinediones / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Caveolin 1; 0/Cholesterol Esters; 0/Enzyme Inhibitors; 0/Hypoglycemic Agents; 0/Immunosuppressive Agents; 0/Organosilicon Compounds; 0/P-Glycoprotein; 0/RNA, Messenger; 0/Thiazolidinediones; 111025-46-8/pioglitazone; 159351-69-6/everolimus; 53123-88-9/Sirolimus; 57-83-0/Progesterone; 57-88-5/Cholesterol; 78934-83-5/SAN 58035; EC 2.3.1.26/Sterol O-Acyltransferase; EC 2.3.1.26/sterol O-acyltransferase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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