Cell-density-dependent methylmercury susceptibility of cultured human brain microvascular pericytes

详细信息    查看全文

• 作者：Takashi Hirooka ; Yasuyuki Fujiwara ; Yuka Minami ; Akihiko Ishii ; Mio Ishigooka ; Yasuhiro Shinkai ; Chika Yamamoto ; Masahiko Satoh ; Akira Yasutake ; Komyo Eto ; Toshiyuki Kaji
• 关键词：Methylmercury ; Pericyte ; Cytotoxicity ; L-type large neutral amino acid transporter 1 ; Glutathione ; Metallothionein
• 刊名：Toxicology in Vitro
• 出版年：2010
• 出版时间：April 2010
• 年：2010
• 卷：24
• 期：3
• 页码：835-841
• 全文大小：632 K

文摘

The knowledge of vascular toxicity is important for understanding the neurotoxicity of methylmercury. In the present study, we investigated the cell-density-dependent susceptibility of human brain microvascular pericytes to methylmercury-induced toxicity by using a cell-culture system. The susceptibility of sparse pericyte cultures to methylmercury was greater than that of the dense cultures. In addition, the sparse cultures were more susceptible to methylmercury than to inorganic mercury and cadmium. The intracellular accumulation of methylmercury in the sparse cells was significantly higher than that in the dense cells. Methylmercury is transported through the L-type large neutral amino acid transporter (LAT 1) in the form of a complex with cysteine. The mRNA- and protein-level expressions of LAT 1 in the sparse cells were markedly higher than those in the dense cells; in addition, the LAT 1 expression was increased by methylmercury. However, there was no reduction in the levels of glutathione and metallothionein, which are involved in the defense mechanisms against methylmercury, in the sparse cells. The present data revealed that pericytes are markedly susceptible to methylmercury-induced cytotoxicity at low cell densities. The susceptibility of the sparse pericytes is postulated to be due to the not only constitutively higher but also methylmercury-induced expression of LAT 1, which increased the intracellular accumulation of methylmercury.