Role of metallothionein against mercury toxicity after exposure to mercury vapor

金属硫蛋白在潜在有毒重金属的代谢和解毒中起着重要作用。本研究旨在(1)研究金属硫蛋白（MT）对汞（Hg）蒸气暴露引起的肺损伤的保护作用；(2)利用MT-null和野生型小鼠阐明胎盘金属硫蛋白在汞蒸气暴露后母体向胎儿汞转移中的作用。首先，研究了MT对汞肺毒性的作用。两种小鼠每天暴露于6.6-7.5 mg/m^3的汞蒸气中4小时，持续3天。该给药方案被发现对超过60%的MT-null小鼠致死，但没有杀死野生型小鼠。组织病理学观察发现，MT-null小鼠的肺损伤比野生型小鼠更严重。汞蒸气暴露使野生型小鼠肺中MT水平显著升高，肺细胞质凝胶过滤显示大多数汞与该蛋白有关。另一方面，在M…More T-null小鼠中，即使在暴露后，MT法仍低于检测限（0.2 μg/g组织）。暴露于汞蒸气3天后，野生型小鼠的肺汞水平显著高于MT-null小鼠。这些发现提示MT对汞蒸气急性肺毒性具有保护作用。第二，研究汞蒸气暴露后MT-null和野生型妊娠小鼠母体向胎儿的汞转移。两系小鼠妊娠后期均暴露于5.5 ~ 6.7 mg/m^3的汞蒸气中3小时。汞蒸气暴露24小时后，MT-null母鼠除脑外各主要脏器中汞的蓄积量均明显低于野生型小鼠。与母体汞水平相反，MT-null小鼠的胎儿汞水平明显高于野生型小鼠。在胎盘中，两个品系小鼠的汞含量没有差异。野生型小鼠暴露于汞蒸气后，胎盘中MT水平升高，胎盘细胞质凝胶过滤显示大量胎盘汞与MT有关。在MT缺失小鼠中，胎盘细胞质中的汞主要出现在高分子量蛋白质部分。这些数据表明，胎盘MT在母婴汞转移中具有保护作用。少

Metallothionein plays important roles in the metabolism and detoxification of potentially toxic heavy metals. This study is to (1) examined a protective role of metallothionein (MT) against the pulmonary damage caused by exposure to mercury (Hg) vapor and (2) clarify the role of placenta metallothionein in maternal to fetal mercury transfer after exposure to Hg vapor using MT-null and wild-type mice. The first, the role of MT against the pulmonary toxicity of Hg is investigated. Both types of mice were exposed to Hg vapor of 6.6-7.5 mg/m^3 4 hours per day for 3 days. This dosing protocol was found lethal to over 60 % of MT-null mice, but did not kill a wild-type mice. The more severe pulmonary damage was found in MT-null mice than in wild type mice by histopathological observation. MT levels in the lung markedly were elevated in wild-type mice by Hg vapor exposure and gel filtration of the lung cytosol revealed that most mercury was associated with this protein. On the other hand, in M … More T-null mice, the level was below the limit of detection (0.2 μg/g tissue) on MT assay even after the exposure. After the exposure to Hg vapor for 3 days, the pulmonary mercury level in wild-type mice was significantly higher than in MT-null mice. These findings suggest that MT plays a protective role against acute pulmonary toxicity of Hg vapor.The second, maternal to fetus transfer of mercury in MT-null and wild-type pregnant mice after Hg vapor exposure is investigated. Both strains mice in late gestation period were exposed to Hg vapor at 5.5 to 6.7 mg/m^3 for 3 hr. Twenty-four hours after Hg vapor exposure, accumulation of mercury in the maj or organs, except brain, of MT-null maternal mice was very lower than in wild-type mice. Contrary to maternal mercury level, fetal mercury levels were significantly higher in MT-null mice than in wild-type mice. In placenta, there was no difference in mercury levels between both strains mice. MT levels in the placenta were elevated in wild-type mice after exposure to Hg vapor, gel filtration of the placental cytosol revealed that a large amount ofplacental mercury was associated with MT. In MT-null mice, mercury in placental cytosol appeared mainly in the high-molecular-weight protein fractions. These data suggest that placental MT has a protective effect in maternal to fetal mercury transfer. Less