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Hyperphosphorylation of microfilament‐associated proteins is involved in microcystin‐LR‐induced toxicity in HL7702 cells
Author(s) -
Zeng Jing,
Tu Weiwei,
Lazar Lissy,
Chen Dongni,
Zhao Jinshun,
Xu Jin
Publication year - 2014
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.21974
Subject(s) - microfilament , microbiology and biotechnology , ezrin , cofilin , cytoskeleton , actin , intermediate filament , phosphorylation , chemistry , hyperphosphorylation , biology , actin cytoskeleton , biochemistry , cell
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. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 981–988, 2015.