Resistance of human brain microvascular endothelial cells in culture to methylmercury: cell-density-dependent defense mechanisms

DOI Web Site Web Site PubMed 被引用文献6件 参考文献51件
  • Hirooka Takashi
    Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University
  • Fujiwara Yasuyuki
    Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University
  • Shinkai Yasuhiro
    Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University
  • Yamamoto Chika
    Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University
  • Yasutake Akira
    National Institute for Minamata Disease
  • Satoh Masahiko
    Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University
  • Eto Komyo
    Health and Nursing Facilities for the Aged, Jushindai, Shinwakai
  • Kaji Toshiyuki
    Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University

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Vascular toxicity is important for understanding the neurotoxicity of methylmercury, because microvessels strongly influence the construction of microenvironment around neurons. Previously, we found that low density-human brain microvascular pericytes are markedly susceptible to methylmercury cytotoxicity due to high expression levels of the L-type amino acid transporter 1 (LAT-1) that transports methylmercury into the cells. Although LAT-1 can be, in general, highly expressed in sparse cells that require amino acids for growth, we found that human brain microvascular endothelial cells, regardless of cell density, were resistant to methylmercury cytotoxicity. To investigate the mechanisms underlying this resistance, we exposed the endothelial cells at low and high cell densities to methylmercury and determined the extent of nonspecific cell damage, intracellular accumulation of methylmercury, expression of LAT-1 and LAT-2 mRNAs, and intracellular expression of reduced glutathione and metallothionein. These experiments indicate that sparse endothelial cells intracellularly accumulate more methylmercury via the highly expressed LAT-1, but are resistant to methylmercury cytotoxicity by higher expression of the protective sulfhydryl peptides, namely, reduced glutathione and metallothionein. It is suggested that both nonspecific and functional damage is caused in pericytes, whereas functional abnormalities rather than nonspecific damage may occur to a greater extent in the endothelial cells in the brain microvessels exposed to methylmercury. The previous and present data also suggest that methylmercury exhibits toxicity in endothelial cells in a manner different from that in pericytes in the brain microvessels.

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