Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain

被引:40
作者
Arthur, Julian R. [1 ]
Heinecke, Karie A. [1 ]
Seyfried, Thomas N. [1 ]
机构
[1] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA
基金
美国国家卫生研究院;
关键词
cholesterol/trafficking; ganglioside; lipid raft; phospholipid/phosphatidylcholine; phospholipid/phosphatidylethanolamine; sphingolipid; storage disease; CYCLODEXTRIN OVERCOMES; BETA-GALACTOSIDASE; CHOLERA-TOXIN; ER STRESS; ACCUMULATION; TRANSPORT; CHROMATOGRAPHY; FIBROBLASTS; ACTIVATION; RESISTANT;
D O I
10.1194/jlr.M012633
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Filipin is an antibiotic polyene widely used as a histochemical marker for cholesterol. We previously reported cholesterol/filipin-positive staining in brain of beta-galactosidase (beta-gal) knockout (-/-) mice (GM1 gangliosidosis). The content and distribution of cholesterol and gangliosides was analyzed in plasma membrane (PM) and microsomal (MS) fractions from whole-brain tissue of 15 week-old control (beta-gal+/-) and GM1 gangliosidosis (beta-gal-/-) mice. Total ganglioside content (mu g sialic acid/mg protein) was 3-fold and 7-fold greater in the PM and MS fractions, respectively, in beta gal-/- mice than in beta gal+/- mice. GM1 content was 30-fold and 50-fold greater in the PM and MS fractions, respectively. In contrast, unesterified cholesterol content (mu g/mg protein) was similar in the PM and the MS fractions of the beta gal-/- and beta gal+/- mice. Filipin is known to bind to various sterol derivatives and phospholipids on thin-layer chromatograms. Biochemical evidence is presented showing that filipin also binds to GM1 with an affinity similar to that for cholesterol, with a corresponding fluorescent reaction. Our data suggest that the GM1 storage seen in the beta-gal-/- mouse contributes to the filipin ultraviolet fluorescence observed in GM1 gangliosidosis brain. The data indicate that in addition to cholesterol, filipin can also be useful for detecting GM1.-Arthur, J. R., K. A. Heinecke, and T. N. Seyfried. Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain. J. Lipid Res. 2011. 52: 1345-1351.
引用
收藏
页码:1345 / 1351
页数:7
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