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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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Total citations by year

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Citations to this article in year 2016 (10)

Title and authors Publication Year
The role of epidermal sphingolipids in dermatologic diseases
S Borodzicz, L Rudnicka, D Mirowska-Guzel, A Cudnoch-Jedrzejewska
Lipids in Health and Disease 2016
Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides
A Kihara
Progress in Lipid Research 2016
Organization of lipids in avian stratum corneum: Changes with temperature and hydration
AM Champagne, HC Allen, RC Bautista-Jimenez, JB Williams
Chemistry and Physics of Lipids 2016
Upregulation of gene expression levels of ceramide metabolic enzymes after application of sphingomyelin-based liposomes to a three-dimensional cultured human epidermis model
Y Itaya, Y Tokudome
Biochemical and Biophysical Research Communications 2016
Delineating pathological pathways in a chemically induced mouse model of Gaucher disease: Characterization of a chemically induced model of Gaucher disease
A Vardi, H Zigdon, A Meshcheriakova, AD Klein, C Yaacobi, R Eilam, BM Kenwood, AA Rahim, G Massaro, AH Merrill, EB Vitner, AH Futerman
The Journal of Pathology 2016
The cutaneous lipid composition of bat wing and tail membranes: a case of convergent evolution with birds
M Ben-Hamo, A Muñoz-Garcia, P Larrain, B Pinshow, C Korine, JB Williams
Proceedings of the Royal Society B: Biological Sciences 2016
Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes
L Cui, Y Jia, ZW Cheng, Y Gao, GL Zhang, JY Li, CF He
Journal of Cosmetic Dermatology 2016
Glycosphingolipid–Protein Interaction in Signal Transduction
D Russo, S Parashuraman, G DAngelo
International journal of molecular sciences 2016
Human as the Ultimate Wound Healing Model: Strategies for Studies Investigating the Dermal Lipidome
DS Wijesinghe, UO Warncke, RF Diegelmann
Current Dermatology Reports 2016
Gaucher disease circa 2016: Progress and ongoing challenges
PK Mistry, G Lopez, R Schiffmann, NW Barton, NJ Weinreb, E Sidransky
Molecular Genetics and Metabolism 2016

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