Tunicamycin inhibits ganglioside biosynthesis in neuronal cells

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Abstract
The antibiotic tunicamycin blocks the transfer of GlcNAc-1-P from UDP-GlcNAc to dolichol phosphate, thereby blocking the synthesis of N-linked oligosaccharide chains on glycoproteins. Its effect on the biosynthesis of gangliosides was not reported. Tunicamycin caused a 70-80% reduction in incorporation of [3H]GlcN into gangliosides and neutral glycosphingolipids of the neuroblastoma-glioma hybrid cell line [rat-mouse] NG 108-15 at antibiotic concentrations that caused a 90% reduction of the radiolabel incorporation into glycoproteins. The effect of tunicamycin on ganglioside biosynthesis was apparent after only 4 h of incubation, and maximum inhibition was seen within 6 h. When control or tunicamycin-treated (5 .mu.g/ml) cells were collected and fractionated to separate glycoproteins, neutral glycosphingolipids, gangliosides and nucleotide sugar-precursor pools, the following results were obtained: UDP-GlcNAc and UDP-GalNAc pool sizes increased > 3-fold, and specific activities decreased 50% upon treatment with tunicamycin; when corrected for this value, the percentage inhibition of GlcN incorporation into various glycoconjugates by tunicamycin in these cells was 82% for glycoproteins, 54% for neutral glycosphingolipids and 50% for gangliosides; the different gangliosides were affected differentially, with the most striking inhibition apparent in GM3 biosynthesis, which was decreased 78% in the presence of tunicamycin. The effects of tunicamycin on glycosphingolipids as well as on glycoproteins must be considered when interpreting its effects on intact cells and organisms.

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