出版社：American Society for Biochemistry and Molecular Biology
摘要：Ceramide is an important constituent of stratum corneum lipids,which act as both physical barriers and signal modulators. Wesynthesized several ceramide derivatives and investigated theireffects on keratinocyte differentiation. RT-PCR and Westernblotting showed that the novel synthetic ceramide derivativesK6PC-4 (N-ethanol-2-hexyl-3-hydroxy-decanamide), K6PC-5, (N-ethanol-3-oxo-2-tetradecyl/hexadecyl-octadecanamide/eicosanamide)andK6PC-9 [N-(1,3-dihydroxypropyl)-2-hexyl-3-oxo-decanamide] markedlyincreased keratin 1 and involucrin expression in normal humanepidermal keratinocytes cultured in vitro. These ceramide derivativeselicited a rapid transient increase in intracellular calciumlevels, which were measured using laser scanning confocal microscopy.In addition, K6PC-4, K6PC-5, and K6PC-9 stimulated the phosphorylationof p42/44 extracellular signal-regulated kinase and c-Jun N-terminalkinase. In a reconstituted epidermis model, K6PC-4, K6PC-5,and K6PC-9 significantly increased keratin 1 expression in thesuprabasal layer. These results indicate that these novel syntheticceramide derivatives have the potential to promote keratinocytedifferentiation, suggesting that the lipid molecules are applicablefor treating skin diseases involving abnormal keratinocyte differentiation.Supplementary key words K6PC-4 • K6PC-5 • K6PC-9 • intracellular calcium level • mitogen-activated protein kinase • keratin 1
