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Citations to this article

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.
W M Holleran, … , P M Elias, E Sidransky
W M Holleran, … , P M Elias, E Sidransky
Published April 1, 1994
Citation Information: J Clin Invest. 1994;93(4):1756-1764. https://doi.org/10.1172/JCI117160.
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Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

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Abstract

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gaucher's disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.

Authors

W M Holleran, E I Ginns, G K Menon, J U Grundmann, M Fartasch, C E McKinney, P M Elias, E Sidransky

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Citations to this article in year 2008 (11)

Title and authors Publication Year
ABCA12 maintains the epidermal lipid permeability barrier by facilitating formation of ceramide linoleic esters
Y Zuo, DZ Zhuang, R Han, G Isaac, JJ Tobin, M McKee, R Welti, JL Brissette, ML Fitzgerald, MW Freeman
The Journal of biological chemistry 2008
Functions of sphingolipid metabolism in mammals — Lessons from genetic defects
F Sabourdy, B Kedjouar, SC Sorli, S Colié, D Milhas, Y Salma, T Levade
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2008
Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism
PM Elias, ML Williams, WM Holleran, YJ Jiang, M Schmuth
Journal of lipid research 2008
Vitamin D receptor and coactivators SRC2 and 3 regulate epidermis-specific sphingolipid production and permeability barrier formation
Y Oda, Y Uchida, S Moradian, D Crumrine, PM Elias, DD Bikle
Journal of Investigative Dermatology 2008
Omega-O-acylceramide, a lipid essential for mammalian survival
Y Uchida, WM Holleran
Journal of Dermatological Science 2008
Topical Peroxisome Proliferator Activated Receptor Activators Accelerate Postnatal Stratum Corneum Acidification
JW Fluhr, MQ Man, JP Hachem, D Crumrine, TM Mauro, PM Elias, KR Feingold
Journal of Investigative Dermatology 2008
β‐Glucocerebrosidase Activity in the Stratum Corneum of House Sparrows following Acclimation to High and Low Humidity
RM Cox, A Muñoz‐Garcia, MS Jurkowitz, JB Williams
Physiological and Biochemical Zoology 2008
Epidermal Ceramidase Activity Regulates Epidermal Desquamation via Stratum Corneum Acidification
E Houben, JP Hachem, KD Paepe, V Rogiers
Skin Pharmacology and Physiology 2008
Acute modulations in permeability barrier function regulate epidermal cornification: role of caspase-14 and the protease-activated receptor type 2
M Demerjian, JP Hachem, E Tschachler, G Denecker, W Declercq, P Vandenabeele, T Mauro, M Hupe, D Crumrine, T Roelandt, E Houben, PM Elias, KR Feingold
The American Journal of Pathology 2008
Dual role of COUP-TF-interacting protein 2 in epidermal homeostasis and permeability barrier formation
O Golonzhka, X Liang, N Messaddeq, JM Bornert, AL Campbell, D Metzger, P Chambon, G Ganguli-Indra, M Leid, AK Indra
Journal of Investigative Dermatology 2008
Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism
PM Elias, ML Williams, WM Holleran, YJ Jiang, M Schmuth
Journal of lipid research 2008

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