Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Department of Bone & Joint Disease, National Center for Geriatrics and Gerontology, Aichi, Japan.
Exp Dermatol. 2018 Aug;27(8):827-832. doi: 10.1111/exd.13497. Epub 2018 Feb 13.
Sphingomyelin synthase (SMS) is an enzyme that generates sphingomyelin (SM) from ceramide (CER) and phosphatidylcholine. SM in the epidermis is a precursor of CER, an important lipid for epidermal permeability barrier function. However, the physiological role of SMS in skin is unclear. To uncover the function of SMS in skin, we investigated sphingolipid metabolism enzyme activity in skin, SM content in the epidermis, CER content in the stratum corneum (SC) and transepidermal water loss (TEWL) as an indicator of barrier function in SMS2-knockout (KO) mice. The activities of sphingolipid metabolism enzymes in skin homogenates were measured using a fluorescently labelled substrate. Enzymatic reaction products were detected by high-performance liquid chromatography (HPLC). Lipids in the epidermis or SC were extracted and quantified by high-performance thin layer chromatography (HPTLC). TEWL was measured using a Tewameter TM300. In SMS2-KO mice, SMS activity in skin homogenates, epidermal SM content and SC CER content were significantly decreased relative to wild-type (WT) mice. The TEWL of SMS2-KO mice was significantly increased compared to WT mice. Our data indicate that SMS2 generates SM in the epidermis and contributes to epidermal permeability barrier function and will support understanding of SM-related metabolic disorders.
鞘氨醇合酶（SMS）是一种酶，可将神经酰胺（CER）和磷脂酰胆碱转化为神经鞘磷脂（SM）。表皮中的 SM 是 CER 的前体，CER 是表皮渗透屏障功能的重要脂质。然而，SMS 在皮肤中的生理作用尚不清楚。为了揭示 SMS 在皮肤中的功能，我们研究了皮肤中鞘脂代谢酶活性、表皮中 SM 含量、角质层（SC）中 CER 含量和作为屏障功能指标的经皮水分流失（TEWL）在 SMS2 敲除（KO）小鼠中的变化。使用荧光标记底物测量皮肤匀浆中鞘脂代谢酶的活性。通过高效液相色谱法（HPLC）检测酶促反应产物。通过高效薄层色谱法（HPTLC）提取和定量测定表皮或 SC 中的脂质。使用 Tewameter TM300 测量 TEWL。在 SMS2-KO 小鼠中，与野生型（WT）小鼠相比，皮肤匀浆中的 SMS 活性、表皮 SM 含量和 SC CER 含量显著降低。SMS2-KO 小鼠的 TEWL 明显高于 WT 小鼠。我们的数据表明，SMS2 在表皮中产生 SM，并有助于表皮渗透屏障功能，将有助于理解与 SM 相关的代谢紊乱。
