Alpha4-overexpressing HL7702 cells can counteract microcystin-LR effects on cytoskeletal structure.

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.