Expression and regulation of GPAT isoforms in cultured human keratinocytes and rodent epidermis
- Biao Lu1,*,
- Yan J. Jiang1,2,†,
- Peggy Kim†,
- Art Moser†,
- Peter M. Elias§,
- Carl Grunfeld† and
- Kenneth R. Feingold†
- *Department of R&D, System Biosciences, Mountain View, CA 94043
- †Metabolism Section and Dermatology, University of California San Francisco, San Francisco, CA 94121
- §Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121
- 2To whom correspondence should be addressed. e-mail: yan.jiang{at}med.va.gov
-
↵1 These authors contributed equally to this work.
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.
Footnotes
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- Abbreviations:
- 1-acyl-sn-glycerol-3-phosphate acyltransferase
- AGPAT
- AT
- all-trans retinoic acid
- 9-cis
- 9-cis retinoic acid
- Cig
- ciglitazone
- CHK
- cultured human keratinocyte
- DGAT
- acyl-CoA: diacylglycerol acyltransferase
- ER
- endoplasmic reticulum
- GPAT
- glycerol-3-phosphate acyltransferase
- GW
- GW 610742X
- LB
- lamellar body
- LXR
- liver X receptor
- mGPAT
- microsomal GPAT
- NEM
- N-ethylmaleimide
- PC
- phosphatidylcholine
- PE
- phosphatidylethanolamine
- PPAR
- peroxisome proliferator-activated receptor
- 22(R)
- 22(R)-OH-cholesterol
- qPCR
- quantitative real-time PCR
- PS
- phosphatidylserine
- RAR
- retinoic acid receptor
- RXR
- retinoid X receptor
- SB
- stratum basale
- SC
- stratum corneum
- SG
- stratum granulosum
- SREBP
- sterol-regulatory element binding protein
- SS
- stratum spinosum
- TEWL
- transepidermal water loss
- TO
- TO 901317
- Tro
- troglitazone
- WT
- wild type
- WY
- WY14643
-
This work was supported by National Institutes of Health Grants AR39448 and AR049932, and the Medical Research Service, Department of Veterans Administration at San Francisco. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies.
- Received March 24, 2010.
- Revision received August 17, 2010.
