Hirooka Takashi, Fujiwara Yasuyuki, Inoue Shoko, Shinkai Yasuhiro, Yamamoto Chika, Satoh Masahiko, Yasutake Akira, Eto Komyo, Kaji Toshiyuki
J Toxicol Sci. 2009 Oct;34(4):433-9. doi: 10.2131/jts.34.433.
Vascular toxicity is an important feature of the neuropathy induced by methylmercury. Methylmercury does not cause nonspecific cell damage, but rather retards the repair of wounded monolayers of cultured human brain microvascular endothelial cells by inhibiting their proliferation. Since vascular endothelial cell proliferation during the repair process strongly depends on the fibroblast growth factor-2 (FGF-2) system, we investigated the effects of methylmercury on the expression of FGF-2 and related proteins (i.e., FGF receptor 1 and perlecan) in cultured human brain microvascular endothelial cells. Of the mRNAs examined, FGF-2 mRNA expression was significantly lowered by methylmercury in not only wounded monolayers but also dense and sparse cultures of endothelial cells; a lower expression of FGF-2 protein in the cells was confirmed. In addition, exogenous FGF-2 partially abrogated the proliferation-inhibitory effect of methylmercury. The results of this study suggest that suppression of FGF-2 expression is one of the mechanisms underlying the inhibitory effect of methylmercury in damaged endothelial cell monolayers. The FGF-2 system may be one of the important biological systems behind the vascular toxicity of methylmercury.
血管毒性是甲基汞所致神经病变的一个重要特征。甲基汞不会造成非特异性细胞损伤，而是通过抑制培养的人脑微血管内皮细胞单层的增殖来延缓其损伤修复。由于修复过程中血管内皮细胞的增殖强烈依赖成纤维细胞生长因子-2（FGF-2）系统，我们研究了甲基汞对培养的人脑微血管内皮细胞中FGF-2及相关蛋白（即FGF受体1和基底膜聚糖）表达的影响。在所检测的mRNA中，甲基汞不仅使损伤的内皮细胞单层，而且使内皮细胞的致密和稀疏培养物中的FGF-2 mRNA表达显著降低；证实细胞中FGF-2蛋白表达较低。此外，外源性FGF-2部分消除了甲基汞的增殖抑制作用。本研究结果表明，FGF-2表达的抑制是甲基汞对受损内皮细胞单层产生抑制作用的机制之一。FGF-2系统可能是甲基汞血管毒性背后的重要生物学系统之一。
