Altered sphingoid base profiles predict compromised membrane structure and permeability in atopic dermatitis.
BACKGROUND
Ceramide hydrolysis by ceramidase in the stratum corneum (SC) yields both sphingoid bases and free fatty acids (FFA). While FFA are key constituents of the lamellar bilayers that mediate the epidermal permeability barrier, whether sphingoid bases influence permeability barrier homeostasis remains unknown. Pertinently, alterations of lipid profile, including ceramide and ceramidase activities occur in atopic dermatitis (AD).


OBJECTIVE
We investigated alterations in sphingoid base levels and/or profiles (sphingosine to sphinganine ratio) in the SC of normal vs. AD mice, a model that faithfully replicates human AD, and then whether altered sphingoid base levels and/or profiles influence(s) membrane stability and/or structures.


METHODS
Unilamellar vesicles (LV), incorporating the three major SC lipids (ceramides/FFA/cholesterol) and different ratios of sphingosine/sphinganine, encapsulating carboxyfluorescein, were used as the model of SC lipids. Membrane stability was measured as release of carboxyfluorescein. Thermal analysis of LV was conducted by differential scanning calorimetry (DSC).


RESULTS
LV containing AD levels of sphingosine/sphinganine (AD-LV) displayed altered membrane permeability vs. normal-LV. DSC analyses revealed decreases in orthorhombic structures that form tightly packed lamellar structures in AD-LV.


CONCLUSIONS
Sphingoid base composition influences lamellar membrane architecture in SC, suggesting that altered sphingoid base profiles could contribute to the barrier abnormality in AD.
Department of Dermatology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Veteran Affairs Medical Center, San Francisco, CA, USA; Northern California Institute for Research and Education, San Francisco, CA, USA; Integrative Toxicology and Metabolism, Pôle de Toxicologie Alimentaire, Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique INRA UR66, Toulouse, France.
Nicolas
N
Loiseau
Yasuko
Y
Obata
Sam
S
Moradian
Hiromu
H
Sano
Saeko
S
Yoshino
Kenichi
K
Aburai
Kozo
K
Takayama
Kazutami
K
Sakamoto
Walter M
WM
Holleran
Peter M
PM
Elias
Yoshikazu
Y
Uchida
D000818:Animals; D002463:Cell Membrane Permeability; D002518:Ceramides / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D051379:Mice; D013110:Sphingosine / Q000378:metabolism*
D002518:Ceramides; D013110:Sphingosine
2,5-carboxyfluorescein; AD; Atopic dermatitis; Barrier; CFC; Cer; Ceramide; DSC; FFA; LV; SC; SDS; Sa; So; Sphingosine; atopic dermatitis; ceramide; differential scanning calorimetry; free fatty acids; sodium dodecyl sulfate; sphinganine; sphingosine; stratum corneum; unilamellar vesicles