文章基本信息

标题：Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments
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作者：Wenchao Zheng ; Natalia Mast ; Aicha Saadane 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2015
卷号：56
期号：1
页码：81-97
DOI：10.1194/jlr.M053439
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholesterol content in the retina and had no significant effect on retinal expression of the major cholesterol- and vision-related genes; the sterol-regulatory element binding protein pathway of transcriptional regulation does not seem to be operative in the retina under the experimental conditions used. Evidence is obtained that posttranslational mechanisms play a role in the control of retinal cholesterol. Retinal genes were only upregulated by oral administrations of TO901317 activating liver X receptors. Three of the upregulated genes could be of particular importance ( apoD , Idol , and Rpe65 ) and have not yet been considered in the context of cholesterol homeostasis in the retina. Collectively, the data obtained identify specific features of retinal cholesterol maintenance and suggest additional therapies for age-related macular degeneration, a blinding disease characterized by cholesterol and lipid accumulations in chorioretinal tissues.
关键词：cytochrome P450 ; transcriptional regulation ; posttranslational regulation ; 3-hydroxy-3-methyl-glutaryl-CoA reductase ; liver X receptor ; sterol-regulatory element binding protein ; RPE65 ; age-related macular degeneration