Department of Biochemistry and Molecular Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Toxicol Lett. 2011 Dec 15;207(3):270-7. doi: 10.1016/j.toxlet.2011.09.025. Epub 2011 Oct 1.
Acute exposure to microcystin-LR (MC-LR) can induce the reorganization or disruption of the cytoskeleton, but proteins or enzymes correlated with this stress response have not been fully identified. Here, we report alterations to HSP27 during MC-LR-induced cytoskeletal reorganization in the human liver cell line HL7702. The cells incubated with MC-LR exhibited the rearrangement of filamentous actins and microtubules. The activity of protein phosphatase 2A was greatly decreased by MC-LR exposure. Furthermore, MC-LR markedly increased the level of HSP27 phosphorylation with the enhanced distribution of phosphorylated HSP27 to the cytoskeleton. To further determine the regulation of MC-LR-induced HSP27 phosphorylation, the activation of the MAPK superfamily was assessed. The result showed phospho-activation of p38 MAPK, JNK and ERK1/2 by MC-LR. Increases in HSP27 phosphorylation were suppressed by pretreating cells with SB203580 or SP600125, which are inhibitors of p38 MAPK or JNK, respectively. These data suggest that phosphorylated HSP27 is involved in cytoskeletal reorganization and is regulated by MAPKs, possibly as a consequence of PP2A inhibition. Moreover, the regulation of HSP27 phosphorylation may be important in MC-LR-induced cytoskeleton reassembly, which may provide helpful insights into the mechanism of MC-LR toxicity.
急性暴露于微囊藻毒素-LR（MC-LR）可诱导细胞骨架的重排或破坏，但与这种应激反应相关的蛋白质或酶尚未完全确定。在这里，我们报告了在人肝癌细胞系 HL7702 中，MC-LR 诱导细胞骨架重排过程中 HSP27 的变化。孵育 MC-LR 的细胞表现出线粒体和微管的丝状肌动蛋白重排。MC-LR 暴露大大降低了蛋白磷酸酶 2A 的活性。此外，MC-LR 显著增加了 HSP27 磷酸化水平，磷酸化 HSP27 向细胞骨架的分布增强。为了进一步确定 MC-LR 诱导的 HSP27 磷酸化的调节，评估了 MAPK 超家族的激活。结果表明，MC-LR 激活了 p38 MAPK、JNK 和 ERK1/2 的磷酸化。用 p38 MAPK 或 JNK 的抑制剂 SB203580 或 SP600125 预处理细胞可抑制 HSP27 磷酸化的增加。这些数据表明，磷酸化 HSP27 参与细胞骨架重排，并受 MAPKs 调节，可能是由于 PP2A 抑制所致。此外，HSP27 磷酸化的调节可能在 MC-LR 诱导的细胞骨架重排中很重要，这可能为 MC-LR 毒性的机制提供有帮助的见解。
