甲基汞是一种环境污染的有机金属化合物,具有神经毒性,如在水峰病患者中观察到的。甲基汞损害水晶病人的周围神经,对感觉神经造成的损害比运动神经更大。周围神经由三种细胞类型组成:背根神经节(DRG)细胞,前角细胞(AHC),和施万细胞。在这项研究中,我们比较了培养的这三种来自大鼠的细胞类型对甲基汞细胞毒性的敏感性,细胞内汞的积累,L型氨基酸转运蛋白1(LAT1)的表达,将甲基汞输送到细胞中,多药耐药相关蛋白2(MRP2)的表达,它将甲基汞-谷胱甘肽缀合物输送到细胞外空间。在检查的细胞中,我们发现DRG细胞对甲基汞最敏感,细胞内汞积累明显较高。与AHC和雪旺氏细胞相比,DRG细胞中LAT1的组成水平较高,MRP2的组成水平较低。此外,由甲基汞引起的细胞生存力下降被LAT1抑制剂显著降低,JPH203,或siRNA介导的LAT1敲低。另一方面,MRP2抑制剂,MK571显着加剧了甲基汞引起的细胞活力降低。我们的结果为水晶病患者周围神经的感觉神经主要损伤提供了细胞基础。
Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.