title: Regulation of heat shock protein 27 phosphorylation during microcystin-LR-induced cytoskeletal reorganization in a human liver cell line.
abstract: Acute exposure to microcystin-LR (MC-LR) can induce the reorganization or disruption of the cytoskeleton, but proteins or enzymes correlated with this stress response have not been fully identified. Here, we report alterations to HSP27 during MC-LR-induced cytoskeletal reorganization in the human liver cell line HL7702. The cells incubated with MC-LR exhibited the rearrangement of filamentous actins and microtubules. The activity of protein phosphatase 2A was greatly decreased by MC-LR exposure. Furthermore, MC-LR markedly increased the level of HSP27 phosphorylation with the enhanced distribution of phosphorylated HSP27 to the cytoskeleton. To further determine the regulation of MC-LR-induced HSP27 phosphorylation, the activation of the MAPK superfamily was assessed. The result showed phospho-activation of p38 MAPK, JNK and ERK1/2 by MC-LR. Increases in HSP27 phosphorylation were suppressed by pretreating cells with SB203580 or SP600125, which are inhibitors of p38 MAPK or JNK, respectively. These data suggest that phosphorylated HSP27 is involved in cytoskeletal reorganization and is regulated by MAPKs, possibly as a consequence of PP2A inhibition. Moreover, the regulation of HSP27 phosphorylation may be important in MC-LR-induced cytoskeleton reassembly, which may provide helpful insights into the mechanism of MC-LR toxicity.
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors: Yu
authors: Y
authors: Sun
authors: Guan-min
authors: GM
authors: Meng
authors: Zong-lou
authors: ZL
authors: Guo
authors: Li-hong
authors: LH
authors: Xu
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D055551:HSP27 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008387:Marine Toxins; D052998:Microcystins / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D055551:HSP27 Heat-Shock Proteins; D008387:Marine Toxins; D052998:Microcystins; D020929:Mitogen-Activated Protein Kinase Kinases; D054648:Protein Phosphatase 2; C057862:cyanoginosin LR