Ceramide (Cer) release from glucosylceramides (GlcCer) is critical for the formation of the skin permeability barrier. Changes in β-glucocerebrosidase (GlcCer'ase) activity lead to diminished Cer, GlcCer accumulation and structural defects in SC lipid lamellae; however, the molecular basis for this impairment is not clear. We investigated impaired GlcCer-to-Cer processing in human Cer membranes to determine the physicochemical properties responsible for the barrier defects. Minor impairment (5-25%) of the Cer generation from GlcCer decreased the permeability of the model membrane to four markers and altered the membrane microstructure (studied by X-ray powder diffraction and infrared spectroscopy), in agreement with the effects of topical GlcCer in human skin. At these concentrations, the accumulation of GlcCer was a stronger contributor to this disturbance than the lack of human Cer. However, replacement of 50-100% human Cer by GlcCer led to the formation of a new lamellar phase and the maintenance of a rather good barrier to the four studied permeability markers. These findings suggest that the major cause of the impaired water permeability barrier in complete GlcCer'ase deficiency is not the accumulation of free GlcCer but other factors, possibly the retention of GlcCer bound in the corneocyte lipid envelope.

• MeSH
• aplikace lokální MeSH
• ceramidy metabolismus   MeSH
• difrakce rentgenového záření MeSH
• elektrická impedance MeSH
• glukosylceramidy aplikace a dávkování   metabolismus   farmakologie   MeSH
• indomethacin farmakokinetika   MeSH
• kůže chemie   účinky léků   metabolismus   MeSH
• lidé MeSH
• membránové lipidy chemie   metabolismus   MeSH
• permeabilita buněčné membrány * účinky léků   MeSH
• permeabilita MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• theofylin farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH