Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.
Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.
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发表时间：
2000-12
影响因子：
6.5
通讯作者：
Y. Uchida;M. Hara;H. Nishio;E. Sidransky;S. Inoue;Fujio Otsuka;Akemi Suzuki;P. Elias;W. Holleran;S. Hamanaka
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作者：
Y. Uchida;M. Hara;H. Nishio;E. Sidransky;S. Inoue;Fujio Otsuka;Akemi Suzuki;P. Elias;W. Holleran;S. Hamanaka
表皮神经酰胺 (Cer) 包含七个物种的异质家族，其中包括两种独特的 omega-羟基化 Cer，它们是负责表皮渗透屏障的角质层 (SC) 细胞间层膜的关键成分。尽管葡萄糖神经酰胺 (GlcCer) 和磷酸鞘脂鞘磷脂 (SM) 都是 SC Cer 的潜在前体，但根据已报道的表皮 GlcCer 和 SC Cer 的化学结构，假设 SC Cer 的所有主要亚组分均由层状体来源的 GlcCer 产生。然而，我们和其他人已经证明，SM 衍生的 Cer 是正常屏障稳态所必需的。此外，两个 SM 池，一个来自质膜，另一个来自层状体衍生内容物，可能可用于 Cer 生产。为了阐明 SM 作为大量或特定 SC Cer 的潜在前体的作用，我们比较了表皮 SM 中的 Cer 部分、通过鞘磷脂酶处理从表皮 SM 生成的 Cer、SC 中的 Cer 以及在戈谢 SC 中持续存在的 Cer，其中 GlcCer 由于缺乏 β-葡萄糖脑苷脂酶而无法生成 Cer。使用气相色谱-质谱、快原子轰击-质谱和核磁共振进行 Cer 表征，表皮 SM 包含三个主要亚组分，具有独特的酰胺连接（N-酰基）脂肪酸（FA）组成：即长链 FA（SM-1；C（22；-26））、短链 FA（SM-2；主要是 C（16））和短链 α-羟基 FA （SM-3；C(16；-18)）。相比之下，仅存在微量的 omega-羟基 FA。对于每个 SM 亚级分，鞘氨醇碱为鞘氨醇或二氢鞘氨醇，但未检测到植物鞘氨醇。这些 SM 与相应的鞘磷脂酶产生的表皮 Cer 和 SC Cer 的比较表明，SM-1 和 SM-3 的 Cer 部分分别相当于 Cer 2 (NS) 和 Cer 5 (AS)。此外，Cer 2 和 Cer 5 均出现在 Gaucher SC 中，而其他 Cer 亚组分则未出现。这些结果表明，两个表皮SM，即SM-1和SM-3，是哺乳动物SC中两个相应Cer，即Cer 2和Cer 5的重要前体，但其他Cer种类，包括omega-羟基Cer种类，并非源自SM。
Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique omega-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of beta-glucocerebrosidase. Using gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C(22;-26)), short-chain FA (SM-2; primarily C(16)), and short-chain alpha-hydroxy FA (SM-3; C(16;-18)). In contrast, only trace quantities of omega-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the omega-hydroxy Cer species, do not derive from SM.