Epidermal ceramidase activity regulates epidermal desquamation via stratum corneum acidification

Skin Pharmacol Physiol. 2008;21(2):111-8. doi: 10.1159/000114872. Epub 2008 Feb 5.


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.

MeSH terms

  • Administration, Topical
  • Amidohydrolases / antagonists & inhibitors
  • Amidohydrolases / metabolism*
  • Animals
  • Ceramidases
  • Desmosomes / physiology
  • Endocannabinoids
  • Epidermis / metabolism
  • Epidermis / physiology*
  • Epidermis / ultrastructure
  • Ethanolamines / pharmacology
  • Fatty Acids, Nonesterified / biosynthesis
  • Homeostasis
  • Hydrogen-Ion Concentration
  • Male
  • Mice
  • Mice, Hairless
  • Oleic Acids
  • Permeability
  • Serine Endopeptidases / metabolism


  • Endocannabinoids
  • Ethanolamines
  • Fatty Acids, Nonesterified
  • Oleic Acids
  • N-oleoylethanolamine
  • Serine Endopeptidases
  • Amidohydrolases
  • Ceramidases