Microcystin-LR promotes cell proliferation in the mice liver by activating Akt and p38/ERK/JNK cascades

Jinghui Liu, Beilei Wang, Pu Huang, Hanying Wang, Kailun Xu, Xiaofeng Wang, Lihong Xu, Zonglou Guo

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Microcystin-LR (MC-LR), a heptapeptide produced by blue-green algae, is shown to induce cytotoxicity by inhibiting protein phosphatase 2A (PP2A) activity. Our previous study revealed that MC-LR promoted cell proliferation in vitro by activating the Akt/mTORC1/S6K1 pathway. This study aims to further investigate the effects of MC-LR on cell proliferation and the correlated mechanisms in vivo. Mice were injected intraperitoneally with 20–80 μg/kg/d MC-LR from 2 h (hours) to 4 d (days). The results showed that the associations of MC-LR with PP2A/C (PP2A C subunit) were concentration-dependent but not time-dependent in the liver, whereas the total PP2A activity was inhibited in both concentration and time dependent manners. The PP2A regulator α4 was found to release its associated PP2A/C as MC-LR bound to PP2A/C. Importantly, 80 μg/kg MC-LR promoted liver cell proliferation beginning at 1 d post exposure, and hyperproliferation also occurred in the 40 μg/kg group at 4 d after exposure. Meanwhile, the Akt/mTORC1/S6K1 and Akt/β-catenin signaling pathways were activated as early as at 2 h post exposure. Furthermore, MC-LR also activated ERK/p38/JNK MAPKs as early as at 2 h post exposure, which was supported by the hyperphosphorylation of their substrates, ATF-2, c-Jun and c-Myc. Interestingly, the total c-Jun and c-Myc levels also increased after MC-LR exposure. These findings indicate that MC-LR can also promote cell proliferation in vivo, and the activation of Akt and MAPK signaling pathways due to PP2A inhibition is proposed to participate in this process.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalChemosphere
Volume163
DOIs
StatePublished - Nov 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • Akt
  • MAPK
  • Microcystin-LR
  • PP2A
  • Proliferation
  • α4

ASJC Scopus subject areas

  • Environmental Engineering
  • General Chemistry
  • Environmental Chemistry
  • Pollution
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Fingerprint

Dive into the research topics of 'Microcystin-LR promotes cell proliferation in the mice liver by activating Akt and p38/ERK/JNK cascades'. Together they form a unique fingerprint.

Cite this