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Permeability barrier requirements regulate epidermal beta-glucocerebrosidase
W M Holleran1, Y Takagi, G K Menon
1Department of Dermatology, University of California School of Medicine, San Francisco.
Journal of Lipid Research
|May 1, 1994
Summary
The enzyme beta-glucocerebrosidase (GlcCer'ase) is crucial for skin barrier function. Inhibiting GlcCer'ase disrupts the skin barrier, highlighting its role in epidermal homeostasis.
Area of Science:
- Biochemistry
- Dermatology
- Molecular Biology
Background:
- The stratum corneum (SC) lipid matrix is vital for the epidermal permeability barrier.
- Ceramides are key lipids in the SC, but their precursors, glucosylceramides (GlcCer), are abundant in the epidermis.
- Hydrolysis of GlcCer to ceramides (Cer) by beta-glucocerebrosidase (GlcCer'ase) may be essential for barrier homeostasis.
Purpose of the Study:
- To investigate if epidermal GlcCer'ase activity and mRNA levels change after skin barrier disruption.
- To determine the effects of GlcCer'ase inhibitors on skin barrier function and SC membrane structure.
Main Methods:
- Assessing epidermal GlcCer'ase mRNA levels and enzyme activity following barrier disruption.
- Localizing GlcCer'ase activity within different epidermal layers.
- Applying a GlcCer'ase inhibitor (bromoconduritol-B-epoxide, BrCBE) topically and evaluating its impact on barrier recovery and SC ultrastructure.
Main Results:
- Barrier disruption significantly increased epidermal GlcCer'ase mRNA levels and overall activity, particularly in the outer epidermis.
- Topical application of BrCBE potently inhibited GlcCer'ase activity and delayed skin barrier recovery.
- BrCBE treatment disrupted the SC intercellular lamellar bilayers without causing cellular toxicity.
Conclusions:
- Epidermal processing of GlcCer to Cer by GlcCer'ase is essential for maintaining skin barrier homeostasis.
- GlcCer'ase activity is regulated in response to barrier disruption.
- Targeting GlcCer'ase may offer therapeutic strategies for barrier repair.