Berring Erin E, Borrenpohl Kimberly, Fliesler Steven J, Serfis Alexa Barnoski
Department of Chemistry, Saint Louis University, Monsanto Hall 125, 3501 Laclede Avenue, St. Louis, MO 63103-2010, USA.
Chem Phys Lipids. 2005 Jul;136(1):1-12. doi: 10.1016/j.chemphyslip.2005.03.004.
Eukaryotic cells require sterols to achieve normal structure and function of their plasma membranes, and deviations from normal sterol composition can perturb these features and compromise cellular and organism viability. The Smith-Lemli-Opitz syndrome (SLOS) is a hereditary metabolic disease involving cholesterol (CHOL) deficiency and abnormal accumulation of the CHOL precursor, 7-dehydrocholesterol (7DHC). In this study, the interactions of CHOL and the related sterols desmosterol (DES) and 7DHC with l-alpha-dipalmitoylphosphatidylcholine (DPPC) monolayers were compared. Pressure-area isotherms and fluorescence microscopy were used to study DPPC monolayers containing 0, 10, 20, or 30 mol% sterol. Similar behavior was noted for CHOL- and DES-containing DPPC monolayers with both techniques. However, while 7DHC gave isotherms similar to those obtained with the other sterols, microscopy indicated limited domain formation with DPPC, indicating that 7DHC packs somewhat differently in DPPC membranes compared to CHOL and DES. These results are discussed in relation to SLOS pathobiology.
真核细胞需要甾醇来实现其质膜的正常结构和功能,甾醇组成偏离正常会扰乱这些特征并损害细胞和生物体的生存能力。史密斯-利姆利-奥皮茨综合征(SLOS)是一种遗传性代谢疾病,涉及胆固醇(CHOL)缺乏和CHOL前体7-脱氢胆固醇(7DHC)的异常积累。在本研究中,比较了CHOL以及相关甾醇去氢胆甾醇(DES)和7DHC与l-α-二棕榈酰磷脂酰胆碱(DPPC)单层的相互作用。使用压力-面积等温线和荧光显微镜研究含有0、10、20或30 mol%甾醇的DPPC单层。两种技术对含CHOL和DES的DPPC单层都观察到了相似的行为。然而,虽然7DHC给出的等温线与其他甾醇相似,但显微镜检查表明其与DPPC形成的结构域有限,这表明与CHOL和DES相比,7DHC在DPPC膜中的堆积方式有所不同。结合SLOS病理生物学对这些结果进行了讨论。