LAUSR

Microcystin‐LR (MC‐LR) is one of the most toxic members of microcystins released by freshwater cyanobacterial. The major mechanism of MC‐LR toxicity has been attributed to its inhibition of protein phosphatases 1 (PP1) and 2A (PP2A). In our prior research, α4 protein, a regulator of PP2A, was found not only crucial for PP2A regulation but also for the overall response of HEK 293 cells encountering MC‐LR. To explore the role of α4 in MC‐LR toxicity via PP2A regulation, here, HEK 293 cells overexpressing α4 protein were exposed to MC‐LR and PP2A, cytoskeletal organization, and cytoskeleton‐related proteins were investigated. The results showed that PP2A activity decreased and PP2A/C subunit expression and phosphorylation at Tyr307 increased significantly in the group exposed to high MC‐LR. Vimentin IF became concentrated and formed perinuclear bundles. However, the assembly of actin filament and microtubules remained unchanged and the expression and phosphorylation of the cytoskeleton‐related proteins HSP27 and VASP did not increase significantly. Some of these results differ from those of our previous study in which normal HEK293 cells were exposed to MC‐LR. Our results indicate that elevated α4 expression confers some resistance to MC‐LR‐induced cytoskeletal change These new findings provide helpful insights into the mechanism of MC‐LR toxicity and the role of α4 in regulating PP2A function. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 255–264, 2017.