期刊
TOXICOLOGY LETTERS
卷 240, 期 1, 页码 214-225出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2015.10.015
关键词
Microcystin-LR; Proliferation; PP2A; alpha 4; Akt/S6K1
类别
资金
- National Nature Science Foundation of China [81172703]
- Key Special Program on the ST of China for the Pollution Control and Treatment of Water Bodies [2012ZX07403-003]
- Medical Scientific Research of Zhejiang Province [2009A044]
Our previous studies had shown that MC-LR inhibited PP2A activity and hyperphosphorylated PP2A substrates at 24 h exposure in HL7702 cells. Although the cytoskeleton was rearranged, the cellular effects were not observed. The purpose of the present study with HL7702 cell exposed to MC-LR for 172 h was to further uncover the adverse effects of MC-LR comprehensively. The results showed that there were no obvious difference in apoptosis rate and cell-cycle distribution but the cell proliferation was changed since 36 h exposure while the uptake of MC-LR and its binding to PP2A/C kept unchanged since 1 h exposure. PP2A activity had not manifested continued decline compare to 24 h exposure and PP2A regulator alpha 4 was found to release its associated PP2A/C since 1 h exposure. The increasing of p-Akt-T308, p-Akt-S473, p-S6K1, p-S6, and p-4E-BP1 since 1 h MC-LR exposure indicated that Akt/S6K1 cascade had been activated as early as 1 h MC-LR treatment. And, PI3K/Akt inhibitor (LY294002) blocked MC-LR-induced Akt/S6K1 activation and proliferation. Besides, MC-LR also led to hyperphosphorylation of c-Myc, c-Jun, Bcl-2 and Bad and activation of Cdk1. Our study indicated that MC-LR exposure promoted HL7702 cell proliferation and the main mechanism was the activation of Akt/S6K1 cascade. Meanwhile, hyperphosphorylation of Bcl-2, Bad, c-Myc and c-Jun might also be involved. And, the inhibition of PP2A was the major reason for these molecular changes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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