Modulation of cell rounding and apoptosis in trigeminal neurinoma cells by protein phosphatase inhibitors.
Modulation of cell rounding and apoptosis in trigeminal neurinoma cells by protein phosphatase inhibitors.
复制标题
蛋白磷酸酶抑制剂对三叉神经神经瘤细胞细胞变圆和细胞凋亡的调节。
作者：
K. Marushige;Y. Marushige
三叉神经鞘瘤476-16细胞暴露于无血清培养基中的C2-神经酰胺诱导细胞变圆，随后细胞死亡，其特征为细胞质收缩和核浓缩。细胞变圆和死亡的诱导发生在增殖细胞中，但不发生在融合培养物的基本静止细胞中。作为神经酰胺处理的结果而形成的台盼蓝不可渗透的圆形细胞在含血清的培养基中在没有神经酰胺的情况下经历凋亡，这表明它们不可逆地致力于细胞死亡。低剂量的蛋白酪氨酸磷酸酶抑制剂，orthovanadate和pervandate抑制神经酰胺诱导细胞变圆，高剂量的pervanadate刺激。蛋白酪氨酸磷酸酶的抑制干扰神经酰胺诱导细胞死亡。蛋白质丝氨酸/苏氨酸磷酸酶抑制剂calyculin A诱导增殖细胞中的细胞变圆。这种细胞变圆不会导致细胞死亡，因此calyculin A抑制神经酰胺诱导细胞死亡。虽然原钒酸盐抑制calyculin A诱导细胞变圆，后者是由神经酰胺增强。神经酰胺和calyculin A的组合在汇合培养物中诱导细胞变圆和细胞死亡。这些结果表明，细胞蛋白的丝氨酸/苏氨酸和酪氨酸的磷酸化的调制密切参与在锚定依赖性细胞的细胞变圆和凋亡的过程。
Exposure of trigeminal neurinoma 476-16 cells to C2-ceramide in a serum-deprived medium induces cell rounding followed by cell death characterized by cytoplasmic shrinkage and nuclear condensation. The induction of cell rounding and death occurs in proliferating cells but not in essentially quiescent cells of confluent cultures. Trypan blue-unpermeable round cells formed as a result of ceramide treatment undergo apoptosis without ceramide in a serum-containing medium, suggesting that they are irreversibly committed to cell death. The induction of cell rounding by ceramide is inhibited by low doses of the protein-tyrosine phosphatase inhibitors, orthovanadate and pervandate, and stimulated by high doses of pervanadate. The inhibition of protein-tyrosine phosphatases interfers the induction of cell death by ceramide. The protein-serine/threonine phosphatase inhibitor calyculin A induces cell rounding in proliferating cells. This cell rounding does not lead to cell death, thus calyculin A inhibits the induction of cell death by ceramide. While orthovanadate inhibits the induction of cell rounding by calyculin A, the latter is potentiated by ceramide. A combination of ceramide and calyculin A induces cell rounding and cell death in confluent cultures. These results demonstrate that modulation of phosphorylation of the serine/threonine and tyrosine of cellular proteins is intimately involved in the process of cell rounding and apoptosis in anchorage-dependent cells.