Department of Biology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.
J Lipid Res. 2011 Jul;52(7):1345-51. doi: 10.1194/jlr.M012633. Epub 2011 Apr 20.
Filipin is an antibiotic polyene widely used as a histochemical marker for cholesterol. We previously reported cholesterol/filipin-positive staining in brain of β-galactosidase (β-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 (β-gal(+/-)) and GM1 gangliosidosis (β-gal(-/-)) mice. Total ganglioside content (μg sialic acid/mg protein) was 3-fold and 7-fold greater in the PM and MS fractions, respectively, in βgal(-/-) mice than in βgal(+/-) mice. GM1 content was 30-fold and 50-fold greater in the PM and MS fractions, respectively. In contrast, unesterified cholesterol content (μg/mg protein) was similar in the PM and the MS fractions of the βgal(-/-) and βgal(+/-) 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 β-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.
菲律宾菌素是一种广泛用于胆固醇组织化学标记的抗生素多烯。我们之前曾报道过β-半乳糖苷酶(β-gal)敲除(-/-)(GM1 神经节苷脂贮积症)小鼠脑中有胆固醇/菲律宾菌素阳性染色。我们分析了来自 15 周龄对照(β-gal(+/-))和 GM1 神经节苷脂贮积症(β-gal(-/-))小鼠全脑组织的质膜(PM)和微粒体(MS)级分中的胆固醇和神经节苷脂的含量和分布。β-gal(-/-)小鼠的 PM 和 MS 级分中总神经节苷脂含量(μg 唾液酸/ mg 蛋白)分别比β-gal(+/-)小鼠高 3 倍和 7 倍。GM1 含量在 PM 和 MS 级分中分别高 30 倍和 50 倍。相比之下,β-gal(-/-)和β-gal(+/-)小鼠的 PM 和 MS 级分中未酯化胆固醇含量(μg/mg 蛋白)相似。菲律宾菌素已知在薄层色谱上与各种固醇衍生物和磷脂结合。本文提供了生化证据表明,菲律宾菌素与 GM1 的结合亲和力与胆固醇相似,具有相应的荧光反应。我们的数据表明,β-gal(-/-)小鼠中观察到的 GM1 贮积导致了 GM1 神经节苷脂贮积症脑内观察到的菲律宾菌素紫外荧光。这些数据表明,除了胆固醇之外,菲律宾菌素还可用于检测 GM1。