Epidermal ceramidase activity regulates epidermal desquamation via stratum corneum acidification.
The acidic pH of the outer surface of the mammalian skin plays several important roles in the epidermal barrier function. The 2 endogenous pathways that are currently known to elicit this acidic pH are the generation of free fatty acids from phospholipids and the exchange of protons for sodium ions by non-energy-dependent sodium-proton exchangers. In this study, we propose a third endogenous pathway, i.e. epidermal ceramidase activity, generating free fatty acids from ceramides. By topical application of N-oleylethanolamine, a well-known ceramidase inhibitor, we could demonstrate a significant increase in the stratum corneum pH and a corresponding decrease in the epidermal free fatty acid content. Moreover, we could show that the resulting change in the apparent skin pH also provoked a delay in early barrier recovery and an increased epidermal desquamation, corresponding to earlier observations made for the already known endogenous mechanisms.
Houben
E
E
Department of Toxicology, Dermatocosmetology and Pharmacognosy, Vrije Universiteit Brussel, Brussels, Belgium. evi.houben@telenet.be
Hachem
J P
JP
De Paepe
K
K
Rogiers
V
V
D000287:Administration, Topical; D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D055572:Ceramidases; D003896:Desmosomes / Q000502:physiology; D063388:Endocannabinoids; D004817:Epidermis / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D004983:Ethanolamines / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009829:Oleic Acids; D010539:Permeability; D012697:Serine Endopeptidases / Q000378:metabolism
D063388:Endocannabinoids; D004983:Ethanolamines; D005230:Fatty Acids, Nonesterified; D009829:Oleic Acids; C033595:N-oleoylethanolamine; D012697:Serine Endopeptidases; D000581:Amidohydrolases; D055572:Ceramidases