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Published on: August 13, 2017
Effect of microcystin-LR on protein phosphatase 2A and its function in human amniotic epithelial cells
Jing Liang1, Tan Li, Ya-Li Zhang
1Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou, China.
Abstract:
Due to their toxicity, the increased distribution of microcystins (MCs) has become an important worldwide problem. MCs have been recognized as inhibitors of protein phosphatase 2A (PP2A) through their binding to the PP2A catalytic subunit. However, the exact mechanism of MC toxicity has not been elucidated, especially concerning the cellular response and its autoregulation. To further dissect the role of PP2A in MC-induced toxicity, the present study was undertaken to determine the response of PP2A in human amniotic epithelial (FL) cells treated with microcystin-LR (MCLR), one of the MC congeners. The results show that a low-dose treatment of MCLR in FL cells for 6 h induced an increase in PP2A activity, and a high-dose treatment of MCLR for 24 h decreased the activity of PP2A, as expected. The increased mRNA and protein levels of the PP2A C subunit may explain the increased activity of PP2A. Furthermore, MCLR altered microtubule post-translational modifications through PP2A. These results further clarify the underlying mechanism how MCLR affects PP2A and may be helpful for elucidating the complex toxicity of MCLR.
Insights
Microcystins (MCs) disrupt protein phosphatase 2A (PP2A) function. This study reveals how microcystin-LR (MCLR) affects PP2A activity and microtubule modifications in human cells, clarifying MC toxicity mechanisms.
Area of Science:
- Environmental Toxicology
- Cellular Biology
- Biochemistry
Background:
- Microcystins (MCs) are toxic cyanobacterial peptides with significant global distribution.
- MCs are known inhibitors of protein phosphatase 2A (PP2A), crucial for cellular regulation.
- The precise mechanisms of MC toxicity, including cellular responses and autoregulation, remain incompletely understood.
Purpose of the Study:
- To investigate the dose- and time-dependent effects of microcystin-LR (MCLR) on PP2A activity in human amniotic epithelial (FL) cells.
- To elucidate the role of PP2A in mediating cellular responses to MCLR exposure.
- To understand how MCLR impacts microtubule post-translational modifications via PP2A.
Main Methods:
- Treatment of FL cells with varying doses and durations of MCLR.
- Assay of PP2A activity.
- Measurement of PP2A C subunit mRNA and protein levels.
- Analysis of microtubule post-translational modifications.
Main Results:
- Low-dose MCLR (6h) increased PP2A activity in FL cells.
- High-dose MCLR (24h) decreased PP2A activity.
- Increased PP2A C subunit mRNA and protein levels correlated with enhanced PP2A activity.
- MCLR exposure altered microtubule post-translational modifications, mediated by PP2A.
Conclusions:
- MCLR exhibits dose- and time-dependent effects on PP2A activity.
- Upregulation of PP2A C subunit contributes to increased activity at lower MCLR doses.
- MCLR-induced alterations in microtubule modifications are linked to PP2A modulation.
- These findings enhance understanding of MCLR's complex toxicity mechanisms.
