Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients with atopic dermatitis
Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients with atopic dermatitis
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DOI：
10.1194/jlr.m200225-jlr200
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发表时间：
2003-01-01
影响因子：
6.5
通讯作者：
Imokawa, G
中科院分区：
文献类型：
--
作者：
Okamoto, R;Arikawa, J;Imokawa, G
为了阐明神经鞘磷脂(SM)脱酰酶与特应性皮炎(AD)神经酰胺缺乏的功能相关性，我们开发了一种新的高度敏感的方法，并测定了积累在角质层中的代谢中间体鞘氨醇(SPC)。从角质层提取的细胞间脂中的SPC与[C-14]乙酸酐反应生成[C-14-C-2]SM，并用TLC对其进行了分析。AD患者皮损和非皮损角质层中SPC含量均显著高于健康对照组。在健康对照组、AD患者皮损和非皮损皮肤中SPC的升高和角质层神经酰胺水平的降低之间存在着相互作用的关系。与角质层中存在的其他鞘磷脂比较表明，SPC与葡萄糖鞘氨醇呈显著正相关，葡萄糖鞘氨醇是另一种由葡萄糖神经酰胺通过另一种新的表皮酶--葡萄糖神经酰胺脱酰酶衍生而来的溶鞘磷脂。相比之下，SPC和鞘氨醇之间没有相关性，鞘氨醇是神经酰胺在神经酰胺酶作用下产生的降解产物。这些发现强烈表明SM脱酰酶在体内的功能与AD患者皮肤中发现的神经酰胺缺乏有关。
To clarify the functional relevance of sphingomyelin (SM) deacylase to the ceramide deficiency seen in atopic dermatitis (AD), we developed a new highly sensitive method and measured the metabolic intermediate sphingo-sylphosphorylcholine (SPC) that accumulates in the stratum corneum. SPC in intercellular lipids extracted from stratum corneum was reacted with [C-14]acetic anhydride to yield [C-14-C-2]SM, which was then analyzed by TLC. In both the lesional and non-lesional stratum corneum obtained from patients with AD, there was a significant increase in the content of SPC over that of healthy control subjects. There was a reciprocal relationship between increases in SPC and decreases in ceramide levels of stratum corneum obtained from healthy controls, and from lesional and non-lesional skin from patients with AD. Comparison with other sphingolipids present in the stratum corneum demonstrated that there is a significant positive correlation between SPC and glucosylsphingosine, another lysosphingolipid derived from glucosylceramide by another novel epidermal enzyme, termed glucosylceramide deacylase. In contrast, there was no correlation between SPC and sphingosine, a degradative product generated from ceramide by ceramidase. These findings strongly suggest the physiological relevance of SM deacylase function in vivo to the ceramide deficiency found in the skin of patients with AD.