LOCALIZATION OF EPIDERMAL SPHINGOLIPID SYNTHESIS AND SERINE PALMITOYL TRANSFERASE-ACTIVITY - ALTERATIONS IMPOSED BY PERMEABILITY BARRIER REQUIREMENTS
LOCALIZATION OF EPIDERMAL SPHINGOLIPID SYNTHESIS AND SERINE PALMITOYL TRANSFERASE-ACTIVITY - ALTERATIONS IMPOSED BY PERMEABILITY BARRIER REQUIREMENTS
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DOI：
10.1007/bf01105075
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发表时间：
1995-03-01
影响因子：
3
通讯作者：
ELIAS, PM
中科院分区：
文献类型：
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作者：
HOLLERAN, WM;GAO, WN;ELIAS, PM
鞘脂是哺乳动物角质层中的主要脂质种类，在通透性屏障稳态中发挥着核心作用。先前的研究表明，表皮合成丰富的鞘脂，这是一个受屏障要求调节的过程，并且抑制鞘脂合成会干扰屏障稳态。为了进一步研究表皮鞘脂代谢与屏障功能之间的关系，我们在基础条件下定位了小鼠表皮中的鞘脂合成活性，并在急性（丙酮处理）或慢性（必需脂肪酸缺乏，EFAD）屏障扰动后，使用二硫苏糖醇和/或葡萄球菌表皮松解毒素将下表皮与外表皮分离。在基础条件下，下表皮和外表皮中丝氨酸棕榈酰转移酶（SPT）（鞘脂合成的限速酶）的活性以及H-3-H2O掺入鞘脂的速率几乎相同。急性屏障扰动后，下表皮层（35%；P < 0.05）和外表皮层（60%；P < 0.01）的 SPT 活性显着增加。在急性屏障破坏后，治疗侧腹下表皮和外表皮中 H-3-H2O 掺入每个主要鞘脂家族（包括神经酰胺、葡萄糖神经酰胺和鞘磷脂）的比率均显着增加。最后，EFAD 动物下表皮中的 SPT 活性适度升高（20%；P < 0.01），但外表皮中没有。这些研究表明，下表皮和外表皮细胞均具有生成鞘脂的能力，并且渗透性屏障稳态机制似乎可以差异性地调节下表皮和外表皮中的 SPT 活性和鞘脂合成，以响应急性和慢性屏障扰动。此外，鞘脂合成的表皮内位点在胆固醇生成的定位和改变方面表现出明显的差异，以响应同等的屏障扰动。
Sphingolipids, the predominant lipid species in mammalian stratum corneum play, a central role in permeability barrier homeostatis. Prior studies have shown that the epidermis synthesizes abundant sphingolipids, a process regulated by barrier requirements, and that inhibition of sphingolipid synthesis interferes with barrier homeostasis. To investigate further the relationship between epidermal sphingolipid metabolism and barrier function, we localized sphingolipid synthetic activity in murine epidermis under basal conditions, and following acute (acetone treatment) or chronic (essential fatty acid deficiency, EFAD) barrier perturbation, using dithiothreitol and/or the staphylococcal epidermolytic toxin to isolate the lower from the outer epidermis. Under basal conditions, both the activity of serine palmitoyl transferase (SPT), the rate-limiting enzyme of sphingolipid synthesis, and the rates of H-3-H2O incorporation into sphingolipids were nearly equivalent in the lower and the outer epidermis. Following acute barrier perturbation, SPT activity increased significantly in both the lower (35%;P < 0.05) and the outer epidermal layers (60%; P < 0.01). The rates of H-3-H2O incorporation into each major sphingolipid family, including ceramides, glucosylceramides and sphingomyelin, increased significantly in both the lower and the outer epidermis of treated flanks after acute barrier disruption. Finally, SPT activity was modestly elevated (20%; P < 0.01) in the lower but not in the outer epidermis of EFAD animals. These studies demonstrate the ability of both lower and outer epidermal cells to generate sphingolipids, and that permeability barrier homeostatic mechanisms appear to differentially regulate SPT activity and sphingolipid synthesis in the lower and the outer epidermis in response to acute and chronic barrier perturbation. Moreover, intraepidermal sites of sphingolipid synthesis displayed distinctive differences in the localization and alterations of cholesterologenesis in response to equivalent barrier perturbations.