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4,8-Sphingadienine and 4-hydroxy-8-sphingenine activate ceramide production in the skin
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Title: | 4,8-Sphingadienine and 4-hydroxy-8-sphingenine activate ceramide production in the skin |
Authors: | Shirakura, Yoshiyuki Browse this author | Kikuchi, Kanako Browse this author | Matsumura, Kenji Browse this author | Mukai, Katsuyuki Browse this author | Mitsutake, Susumu Browse this author →KAKEN DB | Igarashi, Yasuyuki Browse this author →KAKEN DB |
Keywords: | 4,8-sphingadienine | 4-hydroxy-8-sphingenine | Ceramide synthesis |
Issue Date: | 31-Aug-2012 |
Publisher: | BioMed Central |
Journal Title: | Lipids in Health and Disease |
Volume: | 11 |
Start Page: | 108 |
Publisher DOI: | 10.1186/1476-511X-11-108 |
Abstract: | Background: Ingestion of glucosylceramide improves transepidermal water loss (TEWL) from the skin, but the underlying mechanism by which a small amount of dietary glucosylceramide can vastly improve skin conditions remains unclear. In a previous report, glucosylceramides were shown to be digested to sphingoids, which were shown to be absorbed through the intestinal epithelium. Based on these observations, we hypothesized that sphingoids are the key molecules facilitating endogenous ceramide production. In this study, we assessed the effect of 4,8-sphingadienine (d18:2) and 4-hydroxy-8-sphingenine (t18:1), derived from konjac glucosylceramide, on stimulating ceramide production. Methods: Konjac glucosylceramide acidolysis was performed using hydrochloric acid; the resulting d18:2 and t18:1 were fractionated by column chromatography. Real-time quantitative RT-PCR was performed to assess the effect of d18:2 and t18:1 on gene expression in normal human epidermal keratinocytes, while their effect on the nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ, was measured using a receptor-cofactor assay system. The effect of d18:2 and t18:1 on stimulating ceramide production was evaluated using HPTLC analysis in a 3-dimensional human skin model. Results: We noted the upregulation of genes related to de novo ceramide synthesis as well as of those encoding the elongases of very long-chain fatty acids by d18:2 and t18:1, but not by glucosylceramide and 4-sphingenine. Both these sphingoids also facilitated the expression of PPARβ/δ and PPARγ; moreover, they also demonstrated ligand activity for PPARγ. These results indicated that d18:2 and t18:1 promote the differentiation of keratinocytes. Analysis of the lipids within the 3-dimensional human skin model indicated that treatment with d18:2 and t18:1 not only upregulated gene expression but also increased ceramide production. Conclusions: The sphingoids d18:2 and t18:1 activated genes related to de novo ceramide synthesis and increased ceramide production, whereas glucosylceramide and 4-sphingenine could not. These results suggest that the effect of dietary glucosylceramides on the skin is mediated by d18:2 and t18:1. |
Rights: | http://creativecommons.org/licenses/by/2.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/50793 |
Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 五十嵐 靖之
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