Novel synthetic ceramide derivatives increase intracellular calcium levels and promote epidermal keratinocyte differentiation

Jeung-Hoon Lee,Seung Hun Lee,Young-Joon Seo,Jang-Kyu Park,Saewha Jeon,Bo Joong Kim,Byeong Deog Park,Jong-Kyung Youm,Chang Deok Kim,Yoo Bin Kwon,Hyung Sub Gwak

doi:10.1194/jlr.m700185-jlr200

Abstract

Ceramide is an important constituent of stratum corneum lipids, which act as both physical barriers and signal modulators. We synthesized several ceramide derivatives and investigated their effects on keratinocyte differentiation. RT-PCR and Western blotting showed that the novel synthetic ceramide derivatives K6PC-4 [N-(2,3-dihydroxypropyl)-2-hexyl-3-oxo-decanamide], K6PC-5, [N-(1,3-dihydroxypropyl-2-hexyl-3-oxo-decanamide] and K6PC-9 (N-ethanol-2-hexyl-3-oxo-decanamide) [corrected] These ceramide derivatives elicited a rapid transient increase in intracellular calcium levels, which were measured using laser scanning confocal microscopy. In addition, K6PC-4, K6PC-5, and K6PC-9 stimulated the phosphorylation of p42/44 extracellular signal-regulated kinase and c-Jun N-terminal kinase. In a reconstituted epidermis model, K6PC-4, K6PC-5, and K6PC-9 significantly increased keratin 1 expression in the suprabasal layer. These results indicate that these novel synthetic ceramide derivatives have the potential to promote keratinocyte differentiation, suggesting that the lipid molecules are applicable for treating skin diseases involving abnormal keratinocyte differentiation.

Highlights

Ceramide is an important constituent of stratum corneum lipids, which act as both physical barriers and signal modulators
After extracting the alkyl ketene dimer (AKD) from the first reaction, 3-amino-1,2-propanediol [for K6PC-4 (N-ethanol-2-hexyl-3-hydroxy-decanamide)], 2-amino-1,3propanediol [for K6PC-5 (N-ethanol-3-oxo-2-tetradecyl/ hexadecyl-octadecanamide/eicosanamide)], or monoethanolamine [for K6PC-9 (N-[1,3-dihydroxypropy]-2-hexyl-3oxo-decanamide)] was added to the reactor, in which the AKD was agitated with ethanol
The most important function of the stratum corneum is to serve as a physical barrier, and corneocytes and intercellular lipids are key components in this barrier

Summary

Introduction

Ceramide is an important constituent of stratum corneum lipids, which act as both physical barriers and signal modulators. RT-PCR and Western blotting showed that the novel synthetic ceramide derivatives K6PC-4 (N-ethanol-2hexyl-3-hydroxy-decanamide), K6PC-5, (N-ethanol-3-oxo-2tetradecyl/hexadecyl-octadecanamide/eicosanamide)and K6PC-9 [N-(1,3-dihydroxypropyl)-2-hexyl-3-oxo-decanamide] markedly increased keratin 1 and involucrin expression in normal human epidermal keratinocytes cultured in vitro. These ceramide derivatives elicited a rapid transient increase in intracellular calcium levels, which were measured using laser scanning confocal microscopy. In a reconstituted epidermis model, K6PC-4, K6PC-5, and K6PC-9 significantly increased keratin 1 expression in the suprabasal layer These results indicate that these novel synthetic ceramide derivatives have the potential to promote keratinocyte differentiation, suggesting that the lipid molecules are applicable for treating skin diseases involving abnormal keratinocyte differentiation.—Kwon, Y.

Methods

Results

Conclusion