1999 Fiscal Year Final Research Report Summary
Metabolic Pathway of The Formation of Ceramide 1
Project/Area Number |
10670784
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
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Research Institution | Toyama Medical and Pharmaceutical University |
Principal Investigator |
SEKI Taisuke Hospital, Toyama Medical and Pharmaceutical University Assistant Professor, 附属病院, 講師 (30163083)
|
Project Period (FY) |
1998 – 1999
|
Keywords | Ceramide / Epidermis / Keratinization / ω-hydroxylation / Acylceramide / Differentiation / Barrier / Three dimensional culture |
Research Abstract |
The epidermis contains very unique ceramides (Cer), in which very long-chain (C24-32) N-acyl fatty acid groups are omega hydroxylated (ω-OH) that may be esterified to linoleic acid. In the stratum corneum, theseω-hydroxylated Cer, which result from the hydrolysis ofω-OH-glucosylCer precursors, are critical components of the mammalian permeability barrier. To delineate the metabolic pathway for the generation of these unique epidermal ceramides, I determined the effects of both an inhibitor of carbon chain elongation(Minimoidin), and a Cer synthase inhibitor (Fumonisin B1) on the formation ofω-OH-Cer in cultured human keratinocytes. As expected, Minimoidin inhibited the synthesis ofω-OH-Cer. Moreover, Fumonisin B1 blocked both Cer and AcylCer formation, but increasedω-OH free fatty acid fraction, indicating the fatty acid as likely substrate forω-hydroxylation. In summary, these results indicate that the formation ofω-OH ceramides in mammalian epidermis proceeds stepwise, with hydroxylation of very-long chain fatty acids preceding Cer synthesis. Then I measured the amount of Ceramide l(Cer 1 : acylceramide) in three-dimensional culture of mammalian keratinocyte before and after the formation of cornified cell layer. The result indicated that Cer 1 increased with the formation of cornified layer.
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