The role of sphingosylphosphorylchorine generated due to the abnormal expression of sphingomyelin acylase in atopic dermatitis

Yada, Yukihiro; Higuchi, Kazuhiko; Takagi, Yutaka; Imokawa, G.; Murata, Yoshifumi; Higaki, Y.; Kawashima, Makoto

doi:10.1016/0923-1811(94)90331-x

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“…These biological effects may be accompanied by the mobilization of intracellular calcium. More recently, we observed that skin from AD patients exhibits a high activity of SM deacylase, which catalyzes liberation of SPC from SM (30,31), and that cultured normal human keratinocytes also contain significant levels of SM deacylase activity even under nonstimulated conditions (32). Because SPC itself was found at detectable levels in cultured normal human keratinocytes and in normal stratum corneum (32), SPC provides an attractive agonist to explore molecular mechanisms underlying the regulation of keratinization and proliferation in human epidermis.…”

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confidence: 99%

Sphingosylphosphorylcholine is an activator of transglutaminase activity in human keratinocytes

Higuchi

Kawashima

Takagi

et al. 2001

Journal of Lipid Research

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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 M 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 M 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 M 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 dermatitis.

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