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Journal of Lipid Research, Vol. 42, 1562-1570, October 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Sphingosylphosphorylcholine is an activator of transglutaminase activity in human keratinocytes

Kazuhiko Higuchia, Makoto Kawashimaa, Yutaka Takagib, Hidehiko Kondob, Yukihiro Yadab, Yoshiaki Ichikawab, and Genji Imokawab
a Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan
b Kao Biological Science Laboratories, Ichikai-machi 2606, Haga, Tochigi 321-3497, Japan

Correspondence to: Genji Imokawa, To whom correspondence should be addressed., imokawag{at}dream.ocn.ne.jp (E-mail)

We characterize functional roles of a newly discovered chemical, sphingosylphosphorylcholine (SPC), in the epidermis by elucidating the biological effect of SPC on human keratinocytes in culture. The intracellular calcium level of human keratinocytes was increased by incubation with SPC, but not with sphingosine (SS) or sphingomyelin (SM). The addition of SPC, sphingosine 1-phosphate (SSP), or SS to human keratinocytes at 10 µM concentrations also significantly suppressed DNA synthesis, and SPC, but not SSP, or SS increased the activities of membrane-bound and soluble transglutaminases (TGases). Reverse transcription polymerase chain reaction (RT-PCR) of TGase transcripts revealed that SPC treatment at 10 µM concentrations increased the expression of TGase 1 mRNA. The increased activity of soluble TGase was accompanied by the concomitant activation of cathepsin D as revealed by the increased ratio of mature active form to inactive intermediate form of the protease. Pretreatment of human keratinocytes with pepstatin, a protease inhibitor, blocked the increase in soluble TGase activity induced by treatment with SPC. Consistently, SPC treatment at 1–10 µM concentrations stimulated the cornified envelope formation.

These findings suggest that SPC plays an important role in the altered keratinization process of epidermis in skin diseases with high expression of sphingomyelin deacylase, such as atopic der-matitis. — Higuchi, K., M. Kawashima, Y. Takagi, H. Kondo, Y. Yada, Y. Ichikawa, and G. Imokawa. Sphingosylphosphorylcholine is an activator of transglutaminase activity in human keratinocytes. J. Lipid Res. 2001. 42: 1562–1570.

Supplementary key words: sphingomyelin deacylase, atopic dermatitis, sphingolipid, ceramide


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