Holleran W M, Feingold K R, Man M Q, Gao W N, Lee J M, Elias P M
Department of Dermatology, University of California School of Medicine, San Francisco 94121.
J Lipid Res. 1991 Jul;32(7):1151-8.
A mixture of sphingolipids, cholesterol, and free fatty acids forms the intercellular membrane bilayers of the stratum corneum which are presumed to regulate epidermal barrier function. Prior studies have shown that both cholesterol and fatty acid synthesis are rapidly regulated by epidermal barrier requirements. In contrast, the importance of sphingolipids in barrier function has not been directly demonstrated. Here, we have assessed both sphingolipid synthesis by [3H]H2O incorporation and serine palmitoyl transferase (SPT) activity in relation to modulations in barrier function. Incorporation of [3H]H2O into sphingolipids increased after barrier disruption with acetone, with maximal increase (170%) occurring 5-7 h after treatment (P less than 0.005). As barrier function returned to normal over 24 h, incorporation of tritium into sphingolipids normalized. SPT activity also increased after barrier disruption, peaking at 6 h (150%) (P less than 0.05), and returning towards normal by 24 h. Artificial restoration of the barrier with a water vapor-impermeable membrane prevented the increases in both [3H]H2O incorporation into sphingolipids and enzyme activity. Finally, SPT activity was increased in two other models of barrier dysfunction, cellophane tape-stripping and essential fatty acid deficiency. Occlusion normalized SPT activity in both of these models as well. These studies: a) demonstrate a distinctive, delayed increase in epidermal sphingolipid synthesis in response to barrier requirements that contrasts with the immediate responses of cholesterol and fatty acid synthesis; and b) suggest that sphingolipids are important for the maintenance of the epidermal permeability barrier.
鞘脂、胆固醇和游离脂肪酸的混合物形成了角质层的细胞间膜双层结构，据推测该结构可调节表皮屏障功能。先前的研究表明，胆固醇和脂肪酸的合成均受表皮屏障需求的快速调节。相比之下，鞘脂在屏障功能中的重要性尚未得到直接证实。在此，我们通过[3H]H2O掺入法评估了鞘脂合成以及丝氨酸棕榈酰转移酶（SPT）活性与屏障功能调节的关系。用丙酮破坏屏障后，[3H]H2O掺入鞘脂的量增加，处理后5 - 7小时达到最大增幅（170%）（P < 0.005）。随着屏障功能在24小时内恢复正常，氚掺入鞘脂的量也恢复正常。屏障破坏后SPT活性也增加，在6小时达到峰值（150%）（P < 0.05），并在24小时时恢复至正常水平。用不透水蒸气的膜人工恢复屏障可防止[3H]H2O掺入鞘脂和酶活性的增加。最后，在另外两种屏障功能障碍模型（透明胶带剥离和必需脂肪酸缺乏）中，SPT活性也增加。在这两种模型中，封闭处理也使SPT活性恢复正常。这些研究：a）表明表皮鞘脂合成对屏障需求有独特的延迟增加反应，这与胆固醇和脂肪酸合成的即时反应形成对比；b）提示鞘脂对维持表皮通透屏障很重要。
