Regulation of UDP-glucose:ceramide glucosyltransferase-1 by ceramide

We report that the expression of mRNA and the activity of UDP- glucose:ceramide (Cer) glucosyltransferase-1 (GlcT-1) of human hepatoma Huh7 and mouse melanoma B16 cells increases after treatment with bacterial sphingomyelinase or upon addition of short-chain Cer. Interestingly, however, GlcT-1 gene transcription was not increased by Cer when GlcT-1 cDNA was introduced with the CMV promoter in GlcT-1-deficient GM95 cells, suggesting that the normal promoter region of GlcT-1 gene is essential for the response. The conversion of C6-Cer to C6-GlcCer occurred much more rapidly in GlcT-1- overexpressing Huh7 cells than in mock transfectants. As a result, GlcT-1- overexpressing cells acquired a greater resistance to C6-Cer-mediated cell death. (C) 2000 Federation of European Biochemical Societies.