水通道蛋白9在原代小鼠肝细胞中砷的细胞蓄积及其细胞毒性中的作用。
Role of aquaporin 9 in cellular accumulation of arsenic and its cytotoxicity in primary mouse hepatocytes.
作者信息
Shinkai Yasuhiro, Sumi Daigo, Toyama Takashi, Kaji Toshiyuki, Kumagai Yoshito
机构信息
Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa, Ishikawa 920-1181, Japan.
出版信息
Toxicol Appl Pharmacol. 2009 Jun 1;237(2):232-6. doi: 10.1016/j.taap.2009.03.014. Epub 2009 Mar 31.
Aquaporin (AQP) 9 is a member of the aquaglyceroporin subfamily of AQPs in the transfer of water and small solutes such as glycerol and arsenite. It is well recognized that arsenic toxicity is associated with intracellular accumulation of this metalloid. In the present study, we examined the contribution of AQP9 to the uptake of inorganic arsenite, thereby increasing arsenic-induced cytotoxicity in primary mouse hepatocytes. Pretreatment with sorbitol as a competitive inhibitor of AQP9 and siRNA-mediated knockdown of AQP9 resulted in a significant decrease of arsenite uptake in the cell and its cytotoxicity. Furthermore, overexpression of AQP9 in HEK293 cells led to the enhancement of intracellular arsenic concentration, resulting in enhanced cytotoxicity after arsenite exposure. These results suggest that AQP9 is a channel to define arsenite sensitivity in primary mouse hepatocytes.
水通道蛋白9（AQP9）是水通道蛋白甘油通道亚家族的成员之一，参与水和甘油、亚砷酸盐等小分子溶质的转运。众所周知，砷毒性与这种类金属在细胞内的蓄积有关。在本研究中，我们检测了AQP9在无机亚砷酸盐摄取中的作用，从而增加砷诱导的原代小鼠肝细胞的细胞毒性。用山梨醇作为AQP9的竞争性抑制剂进行预处理以及通过小干扰RNA（siRNA）介导敲低AQP9，导致细胞内亚砷酸盐摄取及其细胞毒性显著降低。此外，在人胚肾293（HEK293）细胞中过表达AQP9导致细胞内砷浓度升高，亚砷酸盐暴露后细胞毒性增强。这些结果表明，AQP9是决定原代小鼠肝细胞对亚砷酸盐敏感性的一个通道。
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