Horse-Derived Ceramide Accentuates Glucosylceramide Synthase and Ceramide Synthase 3 by Activating PPARβ/δ and/or PPARγ to Stimulate Ceramide Synthesis

Horse-derived ceramide (HC), which contains galactosylceramides as its main component, significantly improves skin symptoms when applied topically to patients with atopic dermatitis. We speculated that efficacy resulted from the amelioration of epidermal ceramide metabolism, and we characterized tho...

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Published in:Biomedicines 2023-02, Vol.11 (2), p.548
Main Authors: Igarashi, Tami, Yanagi, Hiroki, Yagi, Masayuki, Ichihashi, Masamitsu, Imokawa, Genji
Format: Article
Language:English
Subjects:
Atopic dermatitis
Calcium signalling
Ceramide
Ceramide glucosyltransferase
ceramide synthase 3
Ceramides
Enzymes
fatty acid elongase 4
Fatty acids
galactosylceramide
Gene expression
Glucosylceramidase
glucosylceramide synthase
horse-derived ceramide
Keratinocytes
Lipids
Metabolism
Peroxisome proliferator-activated receptors
Properties
Proteins
Skin diseases
Sphingomyelin
Sphingomyelin phosphodiesterase
Stratum corneum
Western blotting
β-glucocerebrosidase
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Summary:Horse-derived ceramide (HC), which contains galactosylceramides as its main component, significantly improves skin symptoms when applied topically to patients with atopic dermatitis. We speculated that efficacy resulted from the amelioration of epidermal ceramide metabolism, and we characterized those effects using reconstructed human epidermal equivalents. Lipid analysis, RT-PCR and Western blotting revealed that HC significantly increased the total ceramide content of the stratum corneum (SC), accompanied by significantly increased gene and/or protein expression levels of ceramide synthase (CERS) 3, fatty acid elongase (ELOVL) 4, glucosylceramide synthase (GCS), β-glucocerebrosidase, sphingomyelin synthase and acid sphingomyelinase. Mechanistic analyses using cultures of primary human keratinocytes revealed the marked stimulatory effects of HC on the mRNA expression levels of CERS3, ELOVL4 and GCS under high calcium-derived differentiation conditions. Signaling analyses demonstrated that an antagonist of PPARβ/δ significantly abrogated the HC-stimulated mRNA expression levels of GCS, CERS3 and ELOVL4. GW9662, an antagonist of PPARγ, significantly abolished the HC-up-regulated mRNA expression levels of GCS and ELOVL4, but not of CERS3. These findings suggest that HC has the distinct potential to accentuate the expression of GCS, CERS3 and ELOVL4 via the activation of PPARβ/δ and/or PPARγ to accelerate ceramide synthesis in the SC.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines11020548