Microcystin-LR promotes proliferation by activating Akt/S6K1 pathway and disordering apoptosis and cell cycle associated proteins phosphorylation in HL7702 cells

Jinghui Liu, Hao Wang, Beilei Wang, Tao Chen, Xiaofeng Wang, Pu Huang, Lihong Xu, Zonglou Guo

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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 1-72. 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 α4 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.

Original languageEnglish
Pages (from-to)214-225
Number of pages12
JournalToxicology Letters
Volume240
Issue number1
DOIs
StatePublished - Jan 5 2016

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ireland Ltd.

Keywords

  • Akt/S6K1
  • Microcystin-LR
  • PP2A
  • Proliferation
  • α4

ASJC Scopus subject areas

  • Toxicology

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