title: Expression and regulation of GPAT isoforms in cultured human keratinocytes and rodent epidermis.
abstract: Phospholipids are required for epidermal lamellar body formation. Glycerol 3-phosphate acyltransferases (GPATs) catalyze the initial step in the biosynthesis of glycerolipids. Little is known about the expression and regulation of GPATs in epidermis/keratinocytes. Here, we demonstrate that GPAT 1, 3, and 4 are expressed in epidermis/keratinocytes, whereas GPAT2 is not detected. In mouse epidermis, GPAT 3 and 4 are mainly localized to the upper layers whereas GPAT1 is found in both the upper and lower layers. GPAT1 and 3 mRNA increase during fetal rat epidermal development. No change in GPAT expression was observed in adult mice following acute permeability barrier disruption. Calcium-induced human keratinocyte differentiation increased GPAT3 mRNA whereas both GPAT1 and 4 mRNA levels decreased. In parallel, total GPAT activity increased 2-fold in differentiated keratinocytes attributable to an increase in N-ethylmaleimide (NEM) sensitive GPAT activity localized to microsomes with little change in NEM resistant activity, consistent with an increase in GPAT3. Furthermore, PPARγ or PPARδ activators increased GPAT3 mRNA, microsomal GPAT activity, and glycerol lipid synthesis without affecting the expression of GPAT1 or 4. Finally, both PPARγ and PPARδ activators increased GPAT3 mRNA via increasing its transcription. Thus, multiple isoforms of GPAT are expressed and differentially regulated in epidermis/keratinocytes.
authors: Department of R&D, System Biosciences, Mountain View, CA 94043, USA.
authors: Biao
authors: B
authors: Lu
authors: Yan J
authors: YJ
authors: Jiang
authors: Peggy
authors: P
authors: Kim
authors: Art
authors: A
authors: Moser
authors: Peter M
authors: PM
authors: Elias
authors: Carl
authors: C
authors: Grunfeld
authors: Kenneth R
authors: KR
authors: Feingold
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D051381:Rats; D045162:Thiazolidinediones / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D007527:Isoenzymes; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D005992:Glycerol-3-Phosphate O-Acyltransferase; C039671:ciglitazone