Send to

Choose Destination
Chemosphere. 2016 Nov;163:14-21. doi: 10.1016/j.chemosphere.2016.08.002. Epub 2016 Aug 10.

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

Author information

Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Zhejiang Center for Disease Control and Prevention, Hangzhou 310051, China.
Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address:
Department of Biosystem Engineering, College of Biosystem Engineering and Food Science, Zhejiang University, Hangzhou 310058, China. Electronic address:


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.


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

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center