Cortical astrocytes exposed to tributyltin undergo morphological changes in vitro.
Cortical astrocytes exposed to tributyltin undergo morphological changes in vitro.
复制标题
暴露于三丁基锡的皮质星形胶质细胞在体外发生形态变化。
DOI：
10.1254/jjp.84.339
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
N. Matsuki
中科院分区：
文献类型：
--
作者：
S. Mizuhashi;Y. Ikegaya;N. Nishiyama;N. Matsuki
我们研究了三丁基锡（TBT）（一种内分泌干扰化学物质）对培养的大鼠皮质星形胶质细胞的形态和活力的影响。培养的星形胶质细胞在正常条件下表现出光滑、扁平的形态。然而，在暴露于 TBT 后，它们表现出快速的形态变化，其特征是星形细胞体和以时间和浓度依赖性方式形成的过程。较高浓度的 TBT 会导致星形胶质细胞进行性细胞死亡。在无血清培养基中，浓度低至 200 nM 的 TBT 即可诱导星状现象。药理学研究表明，通过使用多种自由基清除剂或抗氧化剂（例如过氧化氢酶、超氧化物歧化酶、Trolox、抗坏血酸和N-乙酰基-L-半胱氨酸）可以减轻形态变化，这表明TBT诱导的星状现象是由自由基（特别是活性氧）参与的氧化应激引起的。此外，我们发现星形胶质细胞星状结构通过磷脂酶C、丝裂原激活蛋白激酶激酶或酪氨酸磷酸酶抑制剂的治疗而被消除。数据表明，TBT 通过细胞内信号级联而不是其非特异性毒性引起星状现象。这些发现为解决哺乳动物对这种环境污染物的厌恶行为的假定问题提供了重要的见解。
We investigated the effect of tributyltin (TBT), an endocrine-disrupting chemical, on the morphology and viability of cultured rat cortical astrocytes. Cultured astrocytes exhibited smooth and planiform morphology under normal conditions. Following exposure to TBT, however, they showed rapid morphological changes that are characterized by asteriated cell bodies and process formation in a time- and concentration-dependent manner. Higher concentrations of TBT produced progressive cell death of the astrocytes. In serum-free medium, TBT at a concentration as low as 200 nM induced the stellation. Pharmacological studies revealed that the morphological changes were alleviated by application of diverse free radical scavengers or antioxidants such as catalase, superoxide dismutase, Trolox, ascorbic acid and N-acetyl-L-cysteine, suggesting that TBT-induced stellation is caused by oxidative stress involving free radicals, particularly reactive oxygen species. Furthermore, we found that the astrocyte stellation was abolished by treatment with inhibitors of phospholipase C, mitogen-activated protein kinase kinase or tyrosine phosphatase. The data suggest that TBT causes the stellation through intracellular signaling cascades rather than its non-specific toxicity. These findings provide an important insight for reconciling the problems in assumed aversive actions of this environmental pollutant for mammals.
酪氨酸磷酸化参与响应血清或 LPA 刺激的肌动蛋白细胞骨架的重组。
影响因子：
4
作者：
Chrzanowska-Wodnicka,M;Burridge,K
通讯作者：
Burridge,K