1-O-acylceramides are natural components of human and mouse epidermis.
The lipid-rich stratum corneum functions as a barrier against pathogens and desiccation inter alia by an unbroken meshwork of extracellular lipid lamellae. These lamellae are composed of cholesterol, fatty acids, and ceramides (Cers) in an equimolar ratio. The huge class of skin Cers consists of three groups: group I, "classical" long and very long chain Cers; group II, ultra-long chain Cers; and group III, ω-esterified ultra-long chain Cers, which are esterified either with linoleic acid or with cornified envelope proteins and are required for the water permeability barrier. Here, we describe 1-O-acylceramides as a new class of epidermal Cers in humans and mice. These Cers contain, in both the N- and 1-O-position, long to very long acyl chains. They derive from the group I of classical Cers and make up 5% of all esterified Cers. Considering their chemical structure and hydrophobicity, we presume 1-O-acylceramides to contribute to the water barrier homeostasis. Biosynthesis of 1-O-acylceramides is not dependent on lysosomal phospholipase A2. However, glucosylceramide synthase deficiency was followed by a 7-fold increase of 1-O-acylceramides, which then contributed 30% to all esterified Cers. Furthermore, loss of neutral glucosylceramidase resulted in decreased levels of a 1-O-acylceramide subgroup. Therefore, we propose 1-O-acylceramides to be synthesized at endoplasmic reticulum-related sites.
Lipid Pathobiochemistry Group within, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mariona
M
Rabionet
Aline
A
Bayerle
Christian
C
Marsching
Richard
R
Jennemann
Hermann-Josef
HJ
Gröne
Yildiz
Y
Yildiz
Dagmar
D
Wachten
Walter
W
Shaw
James A
JA
Shayman
Roger
R
Sandhoff
D000215:Acylation; D000328:Adult; D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008875:Middle Aged; D013045:Species Specificity
D002518:Ceramides
UDP-glucose ceramide glucosyltransferase; ceramide; glucosidase beta 2; lysosomal phospholipase A2; omega-esterified; skin; stratum corneum