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标题：Glucosylceramide synthase activity in murine epidermis: quantitation, localization, regulation, and requirement for barrier homeostasis
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作者：Chujor S. N. Chujor ; Kenneth R. Feingold ; Peter M. Elias 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：1998
卷号：39
期号：2
页码：277-285
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Ceramides, which derive from the hydrolysis of glucosylceramide (GlcCer), are the predominant lipid species in the stratum corneum and are critical for epidermal permeability barrier homeostasis. UDP-glucose:ceramide glucosyltransferase (GlcCer synthase) (EC 2.4.1.80) catalyzes the glucosylation of ceramide to form GlcCer. Recently, we demonstrated a progressive increase in GlcCer synthase expression during fetal barrier development, while others have reported increased GlcCer synthase activity with differentiation of cultured human keratinocytes. To further delineate the role of GlcCer synthase in barrier homeostasis, we determined GlcCer synthase activity and localization in hairless mouse epidermis, both under basal conditions and after acute barrier perturbation. Under basal conditions, GlcCer synthase activity localizes predominantly (∼80%) to the dithiothreitol-separated outer epidermis; i.e., 6.2 ± 0.6 versus 1.2 ± 0.1 pmol/min/mg for outer vs. lower epidermis, respectively ( P threo -1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (P4), a specific GlcCer synthase inhibitor, applied immediately after acute barrier disruption, causes a delay in barrier recovery attributable to specific enzyme inhibition. These findings demonstrate first, that GlcCer synthase activity predominates in the outer epidermis, consistent with an increased formation of GlcCer during barrier ontogenesis and maintenance. Second, GlcCer synthase activity is required for normal permeability barrier homeostasis. Third, baseline epidermal GlcCer synthase activity appears to accommodate acute challenges to the barrier.— Chujor, C. S. N., K. R. Feingold, P. M. Elias, and W. M. Holleran. Glucosylceramide synthase activity in murine epidermis: quantitation, localization, regulation, and requirement for barrier homeostasis. J. Lipid Res. 1998. 39: 277–285.
关键词：epidermis ; ceramides ; sphingolipids ; glucosylceramides ; UDP-glucose:ceramide d -glucosyltransferase ; GlcCer synthase