Biosynthesis of acylceramide in murine epidermis: Characterization by inhibition of glucosylation and deglucosylation, and by substrate specificity

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:122

Article

Takagi, Y ; Nakagawa, H ; Matsuo, N ; Nomura, T ; Takizawa, M ; Imokawa, G

关键词: barrier function;    ceramide;    glucosylceramide;    stratum corneum;    acylation;    omega-hydroxylation;   

DOI  :  10.1111/j.0022-202X.2004.22307.x

来源: Elsevier

【 摘 要 】

We have investigated the physiological significance of the glucosylation of ceramides and the subsequent deglucosylation of glucosylceramide in the synthetic pathway of acylceramide. In this metabolic pathway using [C-14]-serine in organ culture, newborn murine (BALB/c) epidermis synthesizes several types of ceramides, including acylceramide, as analyzed by thin-layer chromatography. When conduritol-B-epoxide, a specific inhibitor of beta-glucocerebrosidase, was added to the culture medium, the synthesis of acylceramide was significantly suppressed in concert with a significant increase in acylglucosylceramide. Furthermore, addition of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosyltransferase, also specifically abolished the synthesis of acylceramide whereas non-acylated ceramides were relatively less affected. We further determined whether the physiological substrate of glucosyltransferase is omega-hydroxyceramide (C30) or non-omega-hydroxylated ceramides. Of those, only non-omega-hydroxylated ceramides proved to be good substrates for glucosyltransferase in vitro. Our parallel in vitro study also demonstrated that murine epidermis contains enzymatic activity by which omega-hydroxyglucosylceramide or omega-hydroxyceramide can be converted to acylglucosylceramide or acylceramide. Collectively, these findings indicate that the majority of acylceramides found in the stratum corneum may be synthesized through a distinct sequence of enzymatic reactions consisting of the glucosylation of ceramides by glucosyltransferase, omega-hydroxylation of glucosylceramide, the acylation of omega-hydroxyglucosylceramide (possibly by an omega-acyltransferase), and the deglucosylation of acylglucosylceramide by beta-glucocerebrosidase.

【 授权许可】

Free