Role of metallothionein against mercury toxicity after exposure to mercury vapor
Role of metallothionein against mercury toxicity after exposure to mercury vapor
批准号:
12670333
负责人:
YOSHIDA Minoru
金额:
$2.18万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 2001
中文摘要
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英文摘要
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
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Takahashi,Y., Tsuruta,S., Hasegawa,J., Kamayama,Y. and Yoshida,M.: "Release of mercury dental amalgam fillings in pregnant rats and distribution of mercury in maternal and fetal tissues"Toxicology. 163. 115-126 (2001)
高桥,Y.,鹤田,S.,长谷川,J.,釜山,Y.
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Nagano,S., Satoh,M., Sumi,H., Fujimura,H., Tohyama,C., Yanagihara,T and Sakoda,S.: "Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose-dependent manner"Eur. J. Neurosci.. 16. 1363-1370 (2
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Yoshida M., et.al.: "Distribution and retention of mercury in metallothionein-null mice after exposure to mercury vapor"Toxicology. 139. 129-136 (1999)
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Fukukoto,M., Kujiraoka,T., Kara,M., Shibahara,T., Hosoya,T. and Yoshida,M.: "Effect of cadmium on gap junctional intercellular communication in primary cultures of rat renal proximal tubular cells"Life Sci.. 69. 247-254 (2001)
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