title: Tributyltin induces disruption of microfilament in HL7702 cells via MAPK-mediated hyperphosphorylation of VASP.
abstract: Tributyltin (TBT) has been widely used for various industrial purposes, and it has toxic effects on multiple organs and tissues. Previous studies have found that TBT could induce cytoskeletal disruption, especially of the actin filaments. However, the underlying mechanisms remain unclear. The aim of the present study was to determine whether TBT could induce microfilament disruption using HL7702 cells and then to assess for the total levels of various microfilament-associated proteins; finally, the involvement of the MAPK pathway was investigated. The results showed that after TBT treatment, F-actin began to depolymerize and lost its characteristic filamentous structure. The protein levels of Ezrin and Cofilin remained unchanged, the actin-related protein (ARP) 2/3 levels decreased slightly, and the vasodilator-stimulated phosphoprotein (VASP) decreased dramatically. However, the phosphorylation levels of VASP increased 2.5-fold, and the ratio of phosphorylated-VASP/unphosphorylated-VASP increased 31-fold. The mitogen-activated protein kinases (MAPKs) ERK and JNK were discovered to be activated. Inhibition of ERK and JNK not only largely diminished the TBT-induced hyperphosphorylation of VASP but also recovered the cellular morphology and rescued the cells from death. In summary, this study demonstrates that TBT-induced disruption of actin filaments is caused by the hyperphosphorylation of VASP through MAPK pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1530-1538, 2016.
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Tu
authors.affiliation: Department of Biochemistry, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.|Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.
authors.forename: Lin-Dan
authors.initials: LD
authors.lastname: Ji
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Qian
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.|Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Zhao
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China. xujin1@nbu.edu.cn.|Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China. xujin1@nbu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008840:Microfilament Proteins / Q000032:analysis / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D014220:Trialkyltin Compounds / Q000633:toxicity*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D014220:Trialkyltin Compounds; D000098662:Vasodilator-Stimulated Phosphoprotein; C011559:tributyltin
keywords: hyperphosphorylation; microfilament; mitogen-activated protein kinase; tributyltin; vasodilator-stimulated phosphoprotein