Cytoskeleton-related Toxicity Mechanism Of Microcystin

In recent years, rapid development of economy has been lead to serious environmentalpollution. Eutrophication is a particularly prominent problem. Many lakes and rivers in ourcountry frequent outbreaks of algal blooms. During blooms, the algae release a large amountof toxins into the water. Microcystin (MC) which released by Microcystis aeruginosa is themost toxic, harmful and widely distributed one used class of toxins. The main targets of MCare liver, kidneys and intestines, and now it is a recognized as a hepatotoxin. MC can causeacute liver hemorrhage, liver necrosis and primary hepatocellular carcinoma. The molecularmechanism of MC-LR hepatotoxicity and cancer-promoting toxicity have been carry outextensive, and have achieved certain results. But the mechanism of MC-LR toxicity has notbeen fully elucidated, especially the role of the cytoskeleton involved is still not clear.Therefore, the present study used the normal human hepatocyte-drived7702cell line to studythe molecular mechanism of MC-LR. After exposure24h with different concentrations ofMC-LR, series of cytological effects, including the morphology, proliferation, cell cycle,apoptosis and cytoskeleton, were detected. Further studies carry on detect the change oftranscription, protein expression and phosphorylation. The results showed that MC-LR couldsignificantly inhibit cell proliferation and induce apoptosis, meanwhile, the actin filamentsand intermediate filaments reorganized. the mRNA levels and protein levels of cytoskeletonfamily members remained unchanged, but the phosphorylation of K8ser74, K18ser52,Vimentin ser56, VASP ser239and VASP ser157residue increased significantly. The resultssuggested that MC-LR can induce hyperphosphorylation of K8/18, Vimentin, VASP inHL7702cells, which subsequently lead to cytoskeleton reorganization and apoptosis. K8/18,Vimentin, VASP proteins are involved in multiple signaling pathways, which may ProvideClues for further study of MC-LR destruction mechanism of the cytoskeleton, and whichskeleton-related protein and signaling pathways may cause by a wider range of toxic effects.