Stahlberg Sören, Školová Barbora, Madhu Perunthiruthy K, Vogel Alexander, Vávrová Kateřina, Huster Daniel
†Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.
‡Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
Langmuir. 2015 May 5;31(17):4906-15. doi: 10.1021/acs.langmuir.5b00751. Epub 2015 Apr 22.
We investigated equimolar mixtures of ceramides with lignoceric acid and cholesterol as models for the human stratum corneum by differential scanning calorimetry and (2)H solid-state NMR spectroscopy. Our reference system consisted of lignoceroyl sphingosine (Cer[NS24]), which represents one of the ceramides in the human stratum corneum. Furthermore, the effect of ceramide acyl chain truncation to 16 carbons as in Cer[NS16] and the loss of the C4 trans double bond as in dihydroceramide Cer[NDS24] were studied. Fully relaxed (2)H NMR spectra were acquired for each deuterated component of each mixture separately, allowing the quantitative determination of the individual lipid phases. At skin temperature, the reference system containing Cer[NS24] is characterized by large portions of each component of the mixture in a crystalline phase, which largely restricts the permeability of the skin lipid barrier. The loss of the C4 trans double bond in Cer[NDS24] leads to the replacement of more than 25% of the crystalline phase by an isotropic phase of the dihydroceramide that shows the importance of dihydroceramide desaturation in the formation of the skin lipid barrier. The truncated Cer[NS16] is mostly found in the gel phase at skin temperature, which may explain its negative effect on the transepidermal water loss in atopic dermatitis patients. These significant alterations in the phase behavior of all lipids are further reflected at elevated temperatures. The molecular insights of our study may help us to understand the importance of the structural parameters of ceramides in healthy and compromised skin barriers.
我们通过差示扫描量热法和（2）H 固体核磁共振光谱法，研究了神经酰胺与二十四烷酸和胆固醇的等摩尔混合物，以此作为人类角质层的模型。我们的参考体系由二十四烷酰鞘氨醇（Cer[NS24]）组成，它代表了人类角质层中的一种神经酰胺。此外，还研究了神经酰胺酰基链截短至 16 个碳（如 Cer[NS16]）以及失去 C4 反式双键（如二氢神经酰胺 Cer[NDS24]）的影响。分别对每种混合物的每个氘代成分获取完全弛豫的（2）H 核磁共振光谱，从而能够定量测定各个脂质相。在皮肤温度下，含有 Cer[NS24]的参考体系的特征是混合物的每种成分在结晶相中所占比例很大，这在很大程度上限制了皮肤脂质屏障的通透性。Cer[NDS24]中 C4 反式双键的缺失导致超过 25%的结晶相被二氢神经酰胺的各向同性相所取代，这表明二氢神经酰胺去饱和在皮肤脂质屏障形成中的重要性。截短的 Cer[NS16]在皮肤温度下大多处于凝胶相，这可能解释了它对特应性皮炎患者经皮水分流失的负面影响。所有脂质相行为的这些显著变化在温度升高时进一步体现出来。我们研究的分子见解可能有助于我们理解神经酰胺结构参数在健康和受损皮肤屏障中的重要性。
