title: Novel synthetic ceramide derivatives increase intracellular calcium levels and promote epidermal keratinocyte differentiation.
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.
authors.affiliation: Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Yoo Bin
authors.initials: YB
authors.lastname: Kwon
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.forename: Jong-Kyung
authors.initials: JK
authors.lastname: Youm
authors.forename: Hyung Sub
authors.initials: HS
authors.lastname: Gwak
authors.forename: Byeong Deog
authors.initials: BD
authors.lastname: Park
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Saewha
authors.initials: S
authors.lastname: Jeon
authors.forename: Bo Joong
authors.initials: BJ
authors.lastname: Kim
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Seo
authors.forename: Jang-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism
chemical_list: D002518:Ceramides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium