Effects of Ceramide and Dihydroceramide Stereochemistry at C-3 on the Phase Behavior and Permeability of Skin Lipid Membranes
Effects of Ceramide and Dihydroceramide Stereochemistry at C-3 on the Phase Behavior and Permeability of Skin Lipid Membranes
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DOI：
10.1021/acs.langmuir.7b03448
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发表时间：
2018-01-09
期刊：
影响因子：
3.9
通讯作者：
Vavrova, Katerina
中科院分区：
文献类型：
--
作者：
Kovacik, Andrej;Pullmannova, Petra;Vavrova, Katerina
神经酰胺（Cer）是皮肤渗透屏障的关键成分。鞘氨醇为基础的CerNS和二氢鞘氨醇为基础的CerNdS（二氢分子）有两个手性中心；然而，正确的立体化学在皮肤屏障Cer中的重要性尚不清楚。我们研究了CerNS和CerNdS的C-3结构在模型皮肤脂质膜组织和通透性中的作用。合成了具有24-C酰基链的非天然l -三o- cerns和l -三o- cernds，并与它们的天然d -红异构体一起被纳入由角质层主要脂质（Cer、游离脂肪酸、胆固醇和硫酸胆固醇）组成的膜中。利用x射线粉末衍射和红外光谱对膜的微观结构进行了研究，并对氘化游离脂肪酸进行了表征。CerNS和CerNdS中C-3构型的反转提高了相变温度，对层状相没有显著影响，但也降低了模型膜中正交填料的比例，减少了脂质混合。与天然CerNS/NdS异构体的膜相比，膜组织的这些变化导致膜通透性从不变到5倍高（取决于通透性标记，即失水、电阻抗、茶碱通量和吲哚美辛通量）。因此，皮肤Cer和二氢Cer的生理d -红细胞立体化学似乎对其正确的屏障功能至关重要。
Ceramides (Cer) are key components of the skin permeability barrier. Sphingosine-based CerNS and dihydrosphingosine-based CerNdS (dihydroCer) have two chiral centers; however, the importance of the correct stereochemistry in the skin barrier Cer is unknown. We investigated the role of the configuration at C-3 of CerNS and CerNdS in the organization and permeability of model skin lipid membranes. Unnatural L-threo-CerNS and L-threo-CerNdS with 24-C acyl chains were synthesized and, along with their natural D-erythro-isomers, incorporated into membranes composed of major stratum corneum lipids (Cer, free fatty acids, cholesterol, and cholesteryl sulfate). The membrane microstructure was investigated by X-ray powder diffraction and infrared spectroscopy, including deuterated free fatty acids. Inversion of the C-3 configuration in CerNS and CerNdS increased phase transition temperatures, had no significant effects on lamellar phases, but also decreased the proportion of orthorhombic packing and decreased lipid mixing in the model membranes. These changes in membrane organization resulted in membrane permeabilities that ranged from unchanged to 5-fold higher (depending on the permeability markers, namely, water loss, electrical impedance, flux of theophylline, and flux of indomethacin) compared to membranes with natural CerNS/NdS isomers. Thus, the physiological D-erythro stereochemistry of skin Cer and dihydroCer appears to be essential for their correct barrier function.