Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation
Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation
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DOI：
10.1016/s0014-5793(04)00274-1
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发表时间：
2004-04-09
期刊：
影响因子：
3.5
通讯作者：
Igarashi, Y
中科院分区：
文献类型：
--
作者：
Mizutani, Y;Kihara, A;Igarashi, Y
二氢鞘氨醇或二氢神经酰胺的C4-羟基化是酵母和哺乳动物细胞中植物鞘脂生物合成的关键反应。小鼠DES 2（mDES 2）最近被克隆，并且当在酵母细胞中表达时显示作为Δ 4-去饱和酶/C4-羟化酶工作。在这里，我们克隆了人类同源的mDES 2，hDES 2，同源性搜索利用BLAST程序。当在HEK 293细胞中表达时，hDES 2表现出对二氢神经酰胺的羟化酶活性。hDES 2的北方印迹分析显示在皮肤、肠和肾中高表达，据报道这些部位具有高水平的植物鞘脂。此外，在维生素C/血清诱导的人角质形成细胞分化过程中，观察到hDES 2 mRNA表达和随后的植物神经酰胺产生的上调。这些结果表明，新克隆的hDES 2在人类皮肤和其他含有植物鞘脂的组织中的植物鞘脂合成中起着重要作用。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The C4-hydroxylation of dihydrosphingosine or dihydroceramide is a key reaction in the biosynthesis of phytosphingolipids, both in yeasts and in mammalian cells. Mouse DES2 (mDES2) was recently cloned and shown to work as a Delta4-desaturase/C4-hydroxylase, when expressed in yeast cells. Here, we cloned a human homologue of mDES2, hDES2, by homology search utilizing a BLAST program. When expressed in HEK 293 cells, hDES2 exhibited hydroxylase activity for dihydroceramide. Northern blot analyses of hDES2 revealed high expression in skin, intestines, and kidney, sites reportedly possessing high levels of phytosphingolipids. Furthermore, up-regulation of hDES2 mRNA expression and subsequent phytoceramide production were observed during vitamin C/serum-induced differentiation of human keratinocytes. These results suggest that the newly cloned hDES2 plays an essential role in phytosphingolipid synthesis in human skin and other phytosphingolipid-containing tissues. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.