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

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

Department of Dermatology, Chungnam National University, School of Medicine, Daejeon 301-040

Corresponding Author: jhoon{at}cnu.ac.kr;cdkimd@cnu.ac.kr

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. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed that the novel synthetic ceramide derivatives, K6PC-4, K6PC-5, and K6PC-9, 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 addition, K6PC-4, K6PC-5, and K6PC-9 stimulated the phosphorylation of p42/44 extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). In a reconstituted epidermis model, K6PC-4, K6PC-5, and K6PC-9 significantly increased keratin 1 expression in 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.

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