Expression and regulation of 1-acyl-sn-glycerol-3-phosphate acyltransferases in the epidermis
Expression and regulation of 1-acyl-sn-glycerol-3-phosphate acyltransferases in the epidermis
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DOI：
10.1194/jlr.m500258-jlr200
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发表时间：
2005-11-01
影响因子：
6.5
通讯作者：
Feingold, KR
中科院分区：
文献类型：
--
作者：
Lu, B;Jiang, YJ;Feingold, KR
磷脂是表皮中的一类主要脂类，它们是维持表皮通透性屏障功能的重要游离脂肪酸的来源。磷脂生物合成酶1-酰基-sn-甘油-3-磷酸酰基转移酶(AGPAT)催化溶血磷脂酸的酰化反应生成磷脂酸，磷脂酸是所有甘油脂的主要前体。我们发现了一种表皮特有的AGPAT亚型的表达模式，其中小鼠AGPAT(MAGPAT)3、4和5的成分表达相对较高，而mAGPAT 1和2的成分表达较低。定位研究表明，所有五种AGPAT亚型都在表皮的所有核层中表达。此外，在大鼠表皮发育后期，随着酶活性的增加和通透性屏障的形成，大鼠AGPAT 2和5mRNAs同时增加。此外，在两种方法破坏通透性屏障后，mAGPAT 1、2和3m RNA水平迅速升高，并持续至少24 h，在m RNA水平升高的同时，AGPAT活性也随之增加。由于磁带剥离后mAGPAT mRNAs的上调可被人工屏障闭塞修复部分逆转，这些研究表明AGPATs表达的增加与屏障要求有关。
Phospholipids are a major class of lipids in epidermis, where they serve as a source of free fatty acids that are important for the maintenance of epidermal permeability barrier function. The phospholipid biosynthetic enzyme, 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT), catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, the major precursor of all glycerolipids. We identified an expression pattern of AGPAT isoforms that is unique to epidermis, with relatively high constitutive expression of mouse AGPAT (mAGPAT) 3, 4, and 5 but low constitutive expression of mAGPAT 1 and 2. Localization studies indicate that all five isoforms of AGPAT were expressed in all nucleated layers of epidermis. Furthermore, rat AGPAT 2 and 5 mRNAs increased in parallel with both an increase in enzyme activity and permeability barrier formation late in rat epidermal development. Moreover, after two methods of acute permeability barrier disruption, mAGPAT 1, 2, and 3 mRNA levels increased rapidly and were sustained for at least 24 h. In parallel with the increase in mRNA levels, an increase in AGPAT activity also occurred. Because upregulation of mAGPAT mRNAs after tape-stripping could be partially reversed by artificial barrier restoration by occlusion, these studies suggest that an increase in the expression of AGPATs is linked to barrier requirements.