title: Valproic acid suppresses G1 phase-dependent sialylation of a 65kDa glycoprotein in the C6 glioma cell cycle.
abstract: The influence of valproate on in vitro glycosylation events in C6 glioma has been investigated, as this major human teratogen restricts proliferation in the mid-G1 phase of the cycle and alters the prevalence and/or glycosylation state of cell surface glycoproteins with the potential to mediate cell-cell and cell matrix interactions critical to development. C6 glioma cultured continuously in the presence of 1 mM valproate exhibited a significant depression of exponential growth but attained confluency one day later, when the majority of cells entered the G1 phase of the cycle. Glycoprotein sialyltransferase, which exhibited a four-fold increase during exponential growth and a small decrease at confluency, was markedly attenuated in valproate-exposed cells in a manner which was indirect. This was associated with an inhibition of transient alpha2,3 sialylation of a 65 kDa glycoprotein expressed maximally at 4 hr into the G1 phase of the cell cycle. This effect was cell-cycle phase-specific, as exposure of synchronized cells to valproate inhibited transient sialylation at 4 and 5 hr into the G1 phase. Inhibition of the 65 kDa glycoprotein sialylation by valproate is suggested to arise from impaired signal transduction preceding the eventual arrest by the drug at a 5-6 hr G1 phase restriction point.
authors.affiliation: Department of Pharmacology, University College, Belfield, Dublin, Ireland.
authors.forename: C L
authors.initials: CL
authors.lastname: Bacon
authors.forename: E
authors.initials: E
authors.lastname: O'Driscoll
authors.forename: C M
authors.initials: CM
authors.lastname: Regan
mesh_terms: D003864:Depression, Chemical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D012799:Sialyltransferases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D014635:Valproic Acid; D012799:Sialyltransferases