Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou, China.
Environ Toxicol. 2018 Sep;33(9):978-987. doi: 10.1002/tox.22585. Epub 2018 Jul 9.
Our previous studies indicated that α4 was involved in the toxicity of MC-LR on the cytoskeleton via the change of PP2A activity in HEK 293. To explore the role of α4 in MC-LR toxicity via PP2A regulation in different cell lines, the HL7702 cell overexpressing α4 protein was exposed to MC-LR, and the change of PP2A, cytoskeletal structure, and cytoskeleton-related proteins were investigated. The results showed that PP2A activity was decreased, PP2A/C subunit expression and phosphorylation (Tyr307) increased significantly, but methylation (Leu 309)clearly decreased. The structure of the actin filaments and microtubules (MTs) remained unchanged, and the expression and phosphorylation of the cytoskeleton-related proteins showed different changes. In addition, the main components of the MAPK pathway, JNK, P38, and ERK1/2, were activated together. Our results indicated that elevated α4 expression did confer some resistance to MC-LR-induced cytoskeletal changes, but the responses of different cell lines to MC-LR, under the α4-overexpression condition, are not exactly the same.
我们之前的研究表明，α4 通过改变 PP2A 活性参与了 MC-LR 对细胞骨架的毒性作用。为了在不同细胞系中通过 PP2A 调节探索 α4 在 MC-LR 毒性中的作用，用 MC-LR 处理过表达 α4 蛋白的 HL7702 细胞，研究了 PP2A、细胞骨架结构和细胞骨架相关蛋白的变化。结果表明，PP2A 活性降低，PP2A/C 亚基表达和磷酸化（Tyr307）显著增加，但甲基化（Leu309）明显减少。肌动蛋白丝和微管（MT）的结构保持不变，细胞骨架相关蛋白的表达和磷酸化显示出不同的变化。此外，MAPK 通路的主要成分 JNK、P38 和 ERK1/2 一起被激活。我们的结果表明，α4 表达水平的升高确实赋予了细胞对 MC-LR 诱导的细胞骨架变化的一定抗性，但在α4 过表达的情况下，不同细胞系对 MC-LR 的反应并不完全相同。
