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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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Research Article Article has an altmetric score of 3

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 2017 (11)

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SGPL1 mutations cause adrenal insufficiency and steroid resistant nephrotic syndrome
Rathi Prasad, Irene Hadjidemetriou, Avinaash Maharaj, Eirini Meimaridou, Federica Buonocore, Moin A Saleem, Jenny Hurcombe, Agnieszka Bierzynska, Eliana Barbagelata, Ignacio Bergadá, Hamilton Cassinelli, Urmi Das, GOSgene GOSgene, Ruth Krone, Bulent Hacihamdioglu, Erkan Sari, Ediz Yesilkaya, Helen L Storr, Maria Clemente, Monica Fernandez-Cancio, Nuria Camats, Nanik Ram, John C. Achermann, Paul Van Veldhoven, Leonardo Guasti, Debora Braslavsky, Tulay Guran, Louise A Metherell
Journal of Clinical Investigation 2017
Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity
M Nagata, Y Izumi, E Ishikawa, R Kiyotake, R Doi, S Iwai, Z Omahdi, T Yamaji, T Miyamoto, T Bamba, S Yamasaki
Proceedings of the National Academy of Sciences 2017
Induced Pluripotent Stem Cell Modeling of Gaucher’s Disease: What Have We Learned?
D Santos, G Tiscornia
International journal of molecular sciences 2017
Gaucher disease: Progress and ongoing challenges
PK Mistry, G Lopez, R Schiffmann, NW Barton, NJ Weinreb, E Sidransky
Molecular Genetics and Metabolism 2017
Corneocyte lipid envelope (CLE), the key structure for skin barrier function and ichthyosis pathogenesis
M Akiyama
Journal of Dermatological Science 2017
Glucocerebrosidase Mutations in Parkinson Disease
G ORegan, RM deSouza, R Balestrino, AH Schapira
Journal of Parkinson's disease 2017
Lysosomal storage diseases
CR Ferreira, WA Gahl
Translational Science of Rare Diseases 2017
Permeability Barrier and Microstructure of Skin Lipid Membrane Models of Impaired Glucosylceramide Processing
M Sochorová, K Staňková, P Pullmannová, A Kováčik, J Zbytovská, K Vávrová
Scientific Reports 2017
The Spectrum of Neurological Manifestations Associated with Gaucher Disease
TR Lal, E Sidransky
Diseases 2017
Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier Function
EN Tessema, T Gebre-Mariam, RH Neubert, J Wohlrab
Skin Pharmacology and Physiology 2017
Glucocerebrosidase deficiency in dopaminergic neurons induces microglial activation without neurodegeneration
FN Soria, M Engeln, M Martinez-Vicente, C Glangetas, MJ López-González, S Dovero, B Dehay, E Normand, M Vila, A Favereaux, F Georges, CL Bianco, E Bezard, PO Fernagut
Human Molecular Genetics 2017

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