Bacon C L, O'Driscoll E, Regan C M
Department of Pharmacology, University College, Belfield, Dublin, Ireland.
Int J Dev Neurosci. 1997 Oct;15(6):777-84. doi: 10.1016/s0736-5748(97)00019-1.
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.
丙戊酸盐对C6胶质瘤体外糖基化事件的影响已得到研究，因为这种主要的人类致畸剂会限制细胞周期G1中期的增殖，并改变细胞表面糖蛋白的发生率和/或糖基化状态，而这些糖蛋白可能介导对发育至关重要的细胞间和细胞与基质间的相互作用。在1 mM丙戊酸盐存在下持续培养的C6胶质瘤表现出指数生长的显著抑制，但在一天后达到汇合状态，此时大多数细胞进入细胞周期的G1期。糖蛋白唾液酸转移酶在指数生长期间增加了四倍，在汇合时略有下降，在暴露于丙戊酸盐的细胞中以间接方式显著减弱。这与在细胞周期G1期4小时时最大表达的65 kDa糖蛋白的瞬时α2,3唾液酸化受到抑制有关。这种效应具有细胞周期阶段特异性，因为将同步化的细胞暴露于丙戊酸盐会在G1期4小时和5小时时抑制瞬时唾液酸化。丙戊酸盐对65 kDa糖蛋白唾液酸化的抑制作用被认为是由于该药物最终在G1期5 - 6小时限制点停滞之前信号转导受损所致。
