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Effect of an Inhibitor of Glucosylceramide Synthesis on Cultured Human Keratinocytes
Author(s) -
Takami Yoshihiro,
Abe Akira,
Matsuda Takayoshi,
Shayman James A.,
Radin Norman S.,
Walter Robert J.
Publication year - 1998
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.1998.tb02353.x
Subject(s) - ceramide , epidermis (zoology) , keratinocyte , glycosphingolipid , cell growth , sphingolipid , biochemistry , microbiology and biotechnology , biology , thymidine , barrier function , chemistry , in vitro , apoptosis , anatomy
Glucosylceramide (GlcCer) is a major glycosphingolipid component of epidermis, which is thought to be related to the barrier function of skin permeability. However, the role of glycosphingolipids in keratinocyte growth and differentiation has not been fully clarified. It has been reported that D‐threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol (PDMP), an inhibitor of GlcCer synthase (EC 2.4.1.80), depletes cells of glycosphingolipids. This inhibitor has been used as a tool for elucidating their functions. In the present study, the effect of PDMP on cultured normal human keratinocytes was investigated. The cells were treated with various concentrations of PDMP. Forty‐eight hours later cell growth, thymidine incorporation, and lipid content were studied. The cell growth and the incorporation of thymidine into cells were inhibited by PDMP in a dose dependent manner. The synthesis of GlcCer was strongly inhibited by PDMP treatment, whereas no significant changes in ceramide level were observed. We concluded that GlcCer in epidermis may play an important role in regulating epidermal growth and suggested that PDMP may be beneficial for treating proliferative skin disorders in the future.