Regulation of Glycosphingolipid Anabolism in Fibroblasts by Ionophores, Plasma Membrane ATP-ase Inhibition, and Growth Factors
We have undertaken studies on the effects of a monovalent cation transporter (monensin) on the anabolism of plasma membrane glycosphingolipids in human fibroblasts, and made comparisons with related (cat)ionophores, and with epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA). Monensin at a concentration of 10 nanomoles per litre of growth medium caused a great increase in the cellular content of glucosyl and lactosyl ceramide, and marked inhibition of incorporation of labelled galactose into ganglio-sides as well as globotriaosyl- and globotetraosyl ceramides. The plasma membrane sodium-potassium ion ATP-ase inhibitor, ouabain, and the calcium ionophore, A23187, had an effect similar to monensin although less effective. TMB-8, an intracellular calcium antagonist, induced an increase in [3H]Gal incorporation, after epimerization, into glucosyl ceramide. Cyclic AMP had no significant effect on these glycosphingolipids or on the changes induced by monensin. PMA induced a higher incorporation of labelled galactose into almost all glycosphingolipids; EGF showed no effect. Ionic flux should influence the anabolic composition of plasma membrane glycosphingolipids, and this effect may be independent from that of mitogenic growth factors.
KeywordsEpidermal Growth Factor Dibutyryl cAMP Sphingolipid Synthesis Cellular cAMP Level Mitogenic Growth Factor
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