Monger D J, Williams M L, Feingold K R, Brown B E, Elias P M
Dermatology Service, Veterans Administration Medical Center, San Francisco, CA.
J Lipid Res. 1988 May;29(5):603-12.
The end-product of epidermal differentiation is a stratified layer of corneocytes whose extracellular lipid bilayers provide a permeability barrier. It is generally accepted that the epidermis synthesizes most if not all of the lipids found in this tissue and that extra-epidermal tissues contribute very little to this lipid content. Moreover, the individual epidermal strata in which epidermal lipid biosynthesis occurs are not known. To address this question, we examined [3H]H2O incorporation into nonsaponifiable and saponifiable lipids in individual epidermal cell layers 3 hr after intraperitoneal injection into neonatal mice, and compared this to protein and DNA synthesis using intraperitoneal [3H]leucine and [3H]thymidine incorporation, respectively. Lipid biosynthesis was also assessed by [14C]acetate incorporation into lipid fractions in organ cultured skin and in epidermal subpopulations. The in vivo studies demonstrated that the biosynthetic activity of both saponifiable and nonsaponifiable lipids was comparable to, if not greater, in the stratum granulosum (SG) than in basal/spinous (SB + SS) layer, despite significantly lower levels of both protein and DNA synthesis in the SG. On a mass basis, the SG accounts for about four times the biosynthetic activity of the combined SB + SS layers. The lipid biosynthetic activity in vitro also was two- to fivefold higher in the SG, regardless of whether the epidermis was separated into individual cell layers before or after incubations with radiolabel. Moreover, this difference could not be ascribed to increased acetate pools or to elevated metabolism in the SG versus the SB + SS since the rates of CO2 production were much lower in the SG fraction. The increase in lipid biosynthesis in SG over SB + SS was greatest for phospholipids, followed by glycosphingolipids, and free sterols but was observed in almost all lipid classes. These studies show not only that mammalian epidermis is an active site of de novo lipid biosynthesis, but also that this activity remains high in the stratum granulosum, while other forms of metabolic activity are diminishing. These observations are consistent with the knowledge that lipids extruded from the stratum granulosum layer provide the hydrophobic permeability barrier, and further suggest that elevated synthetic activity in the stratum granulosum would allow rapid replenishment in the event that the barrier is damaged.
表皮分化的终产物是一层角质形成细胞，其细胞外脂质双分子层构成了渗透屏障。人们普遍认为，表皮合成了该组织中大部分（即便不是全部）的脂质，而表皮外组织对这种脂质含量的贡献微乎其微。此外，表皮脂质生物合成发生在哪些具体的表皮层尚不清楚。为了解决这个问题，我们在给新生小鼠腹腔注射后3小时，检测了[3H]H2O掺入各表皮细胞层中非皂化和可皂化脂质的情况，并分别使用腹腔注射[3H]亮氨酸和[3H]胸苷掺入法，将其与蛋白质和DNA合成情况进行比较。脂质生物合成还通过[14C]乙酸盐掺入器官培养皮肤和表皮亚群中的脂质组分来评估。体内研究表明，尽管颗粒层（SG）中的蛋白质和DNA合成水平显著低于基底/棘层（SB + SS），但颗粒层中可皂化和非皂化脂质的生物合成活性与基底/棘层相当，甚至更高。以质量计算，颗粒层的生物合成活性约为基底/棘层总和的四倍。体外脂质生物合成活性在颗粒层中也高出两到五倍，无论表皮在与放射性标记物孵育之前还是之后被分离成单个细胞层。此外，这种差异不能归因于颗粒层中乙酸盐池的增加或代谢的升高，因为颗粒层组分中二氧化碳的产生速率要低得多。颗粒层中脂质生物合成相对于基底/棘层的增加在磷脂中最为显著，其次是糖鞘脂和游离固醇，但几乎在所有脂质类别中都有观察到。这些研究不仅表明哺乳动物表皮是从头合成脂质的活跃部位，而且还表明这种活性在颗粒层中仍然很高，而其他形式的代谢活性正在减弱。这些观察结果与从颗粒层挤出的脂质提供疏水渗透屏障的认识一致，并且进一步表明颗粒层中合成活性的升高将允许在屏障受损时迅速补充。
