title: Hyperphosphorylation of microfilament-associated proteins is involved in microcystin-LR-induced toxicity in HL7702 cells.
abstract: Microcystin-LR (MC-LR) has been regarded as a hepatotoxin, which can cause cytoskeletal reorganization, especially of the actin filaments. However, the underlying mechanisms remain unclear. In this study, whether MC-LR could induce microfilaments disruption was verified in the normal human liver cell line HL7702; and then the transcription, translation, and phosphorylation levels of major microfilament-associated proteins were measured; finally, the underlying mechanisms was investigated. After treatment with MC-LR, the actin filaments lost their characteristic filamentous organization in the cells, demonstrating increased actin depolymerization. The mRNA and protein levels of ezrin, vasodilator-stimulated phosphoprotein (VASP), actin-related protein2/3, and cofilin remained unchanged. However, the phosphorylation levels of ezrin and VASP were increased, when treated with 10 μM MC-LR. Moreover, P38 and ERK1/2 were involved in MC-LR-induced hyperphosphorylation of microfilament-associated proteins. In summary, this study demonstrates that MC-LR can cause disruption of actin filaments in HL7702 cells due to MC-LR-induced mitogen-activated protein kinase pathway activation and hyperphosphorylation of different types of microfilament-associated proteins.
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, 315211, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, 315211, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Tu
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, 315211, China.
authors.forename: Lissy
authors.initials: L
authors.lastname: Lazar
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, 315211, China.
authors.forename: Dong-Ni
authors.initials: DN
authors.lastname: Chen
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, 315211, China.|Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, 315211, China.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Zhao
authors.affiliation: Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, 315211, China.|Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, 315211, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008387:Marine Toxins / Q000633:toxicity*; D052998:Microcystins / Q000633:toxicity*; D008840:Microfilament Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000098662:Vasodilator-Stimulated Phosphoprotein; D000099149:Ezrin
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008387:Marine Toxins; D052998:Microcystins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098662:Vasodilator-Stimulated Phosphoprotein; D000099149:Ezrin; C057862:cyanoginosin LR
keywords: actin; hyperphosphorylation; microcystin-LR; microfilament; mitogen-activated protein kinase