Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes.
Asah
Dga1p
Dgat2
Farber disease
Lcat
Lpla2
Lro1p
acyl
acyltransferase
brain
ceramides
epidermis
heart
kidney thymus
liver
lung
lymph node
mammals
skin barrier
spleen
Journal
Lipids
ISSN: 1558-9307
Titre abrégé: Lipids
Pays: United States
ID NLM: 0060450
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
11
03
2022
received:
18
01
2022
accepted:
11
03
2022
pubmed:
24
3
2022
medline:
10
5
2022
entrez:
23
3
2022
Statut:
ppublish
Résumé
1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). Overall levels of 1-OACs did not decrease in any mouse model. In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed.
Substances chimiques
Ceramides
0
Fatty Acids
0
Water
059QF0KO0R
CERS4 protein, mouse
EC 2.3.1.24
Sphingosine N-Acyltransferase
EC 2.3.1.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
183-195Informations de copyright
© 2022 The Authors. Lipids published by Wiley Periodicals LLC on behalf of AOCS.
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