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Journal of Lipid Research, Vol. 46, 2448-2457, November 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Expression and regulation of 1-acyl-sn-glycerol- 3-phosphate acyltransferases in the epidermis

Biao Lu, Yan J. Jiang, Mao Q. Man, Barbara Brown, Peter M. Elias and Kenneth R. Feingold¹

Dermatology and Medicine Services, Veterans Administration Medical Center and University of California School of Medicine, San Francisco, CA 94121

Published, JLR Papers in Press, September 8, 2005. DOI 10.1194/jlr.M500258-JLR200

¹ To whom correspondence should be addressed. e-mail: kfngld{at}itsa.ucsf.edu

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.

Supplementary key words lamellar body • phospholipids • epidermal permeability barrier

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