Effect of microcystin-LR on protein phosphatase 2A and its function in human amniotic epithelial cells

• Published in: Journal of Zhejiang University. B. Science Vol. 12; no. 12; pp. 951 - 960
• Main Authors: Liang, Jing, Li, Tan, Zhang, Ya-li, Guo, Zong-lou, Xu, Li-hong
• Format: Journal Article
• Language: English
• Published: Heidelberg SP Zhejiang University Press 01.12.2011; Springer Nature B.V; Zhejiang University Press
• Subjects: Amnion - cytology; Amnion - drug effects; Amnion - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Catalytic subunits; Cell Line; Dose-Response Relationship, Drug; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; Microcystins - administration & dosage; Microcystins - pharmacokinetics; Protein Phosphatase 2 - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; B55α; Tubulin; Q26; Phosphatase activity; Microcystin-LR; Hormesis; Protein phosphatase 2A
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B1100121

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.