Methylmercury Induces Cytotoxicity through Inhibition of PTEN Activity by a Decrease in Its Solubility

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  • Kobayashi Takumi
    Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Toyama Takashi
    Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Lee Jin-Yong
    Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University
  • Miura Nobuhiko
    Division of Health Effects Research, Japan National Institute of Occupational Safety and Health
  • Kuge Shusuke
    Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University
  • Naganuma Akira
    Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Hwang Gi-Wook
    Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University

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<p>Methylmercury is a major environmental pollutant that exhibits neurotoxicity. We previously reported that proteolytic systems such as the ubiquitin–proteasome system (UPS) and autophagy are involved in methylmercury toxicity. It is known that the intercellular level of PTEN, a phosphatase involved in autophagy inhibition, is regulated by the UPS. In this study, we coincidentally found that the PTEN level was decreased by methylmercury in the lysate solubilized with RIPA buffer containing 0.1% sodium dodecyl sulfate (SDS). However, the decrease in PTEN level caused by methylmercury was scarcely observed in RIPA buffer containing 2% SDS. These results suggest that methylmercury lowers the solubility of PTEN protein. Moreover, phosphorylation of Akt, a protein kinase that is negatively controlled via PTEN, was accelerated in accordance with a decrease in PTEN protein solubility. This suggests that methylmercury may inhibit PTEN activity by decreasing its solubility. Moreover, PTEN overexpression confers resistance to methylmercury in SH-SY5Y neuroblastoma cells. These results suggest that PTEN is a novel factor involved in reducing methylmercury toxicity and that methylmercury inhibits PTEN activity by decreasing the solubility of PTEN protein, thereby increasing cytotoxicity.</p>

Journal

  • BPB Reports

    BPB Reports 1 (1), 1-5, 2018

    The Pharmaceutical Society of Japan

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