Horse-Derived Ceramide Accentuates Glucosylceramide Synthase and Ceramide Synthase 3 by Activating PPARß/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 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), ß-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 PPARß/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 PPARß/δ and/or PPARγ to accelerate ceramide synthesis in the SC.

Placental extracts regulate melanin synthesis in normal human melanocytes with alterations of mitochondrial respiration.

Placental extracts have been widely used as skin lightening agents in the Japanese cosmetic market. Here, we show that placental extracts contain factors that can decrease or increase melanin synthesis by normal human melanocytes in vitro in possible association with mitochondrial respiration. When normal human melanocytes were treated with a whole porcine placental extract, melanin synthesis was decreased. In contrast, a porcine placental extract in which exudates and insoluble materials including lipids had been removed increased melanin synthesis. In addition, the amount of tyrosinase, the enzyme critical for melanin synthesis, changed in accordance with the alteration of melanin synthesis. Interestingly, the amount of manganese-dependent superoxide dismutase (MnSOD), a mitochondrial-resident antioxidant enzyme, was increased when melanin synthesis was decreased by the whole placental extract. Mitochondrial respiration and glycolysis also changed following treatment with the placental extracts. These results suggest that placental extracts contain factors that can increase or decrease melanin synthesis by normal human melanocytes and that mitochondrial function may be associated with the placental extract-induced regulation of melanogenesis.