Autor: |
Mariona Rabionet, Pauline Bernard, Melanie Pichery, Christian Marsching, Aline Bayerle, Shaalee Dworski, Mustafa A. Kamani, Chandramohan Chitraju, Nina L. Gluchowski, Katlyn R. Gabriel, Abolfazl Asadi, Philipp Ebel, Menno Hoekstra, Sabrina Dumas, James M. Ntambi, Anders Jacobsson, Klaus Willecke, Jeffrey A. Medin, Nathalie Jonca, Roger Sandhoff |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
LipidsREFERENCES. 57(3) |
ISSN: |
1558-9307 |
Popis: |
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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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