Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice.
Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice.
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DOI：
10.1093/jn/126.7.1782
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发表时间：
1996-07
期刊：
影响因子：
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通讯作者：
Edward J. Kelly;C. Quaife;G. Froelick;R. Palmiter
中科院分区：
文献类型：
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作者：
Edward J. Kelly;C. Quaife;G. Froelick;R. Palmiter
金属硫蛋白（MT）结合的锌积累时，动物暴露于过量的锌和锌缺乏的条件下耗尽，这表明MT作为一种手段，隔离多余的锌，以及锌水库，可以利用锌缺乏时。为了研究MT对这些过程的重要性，创建了MT I和MT II基因均为无效等位基因的小鼠，并评估了多个器官的锌浓度和组织学外观。在出生时，这些MT缺失小鼠的肝脏锌浓度低于野生型对照组（0.27 +/- 0.02对0.65 +/- 0.11微摩尔锌/g组织，P < 0.05）。在接下来的3周哺乳期锌充足（95微克锌/克饲料）母鼠，对照组的肝脏锌浓度降至0.42 +/- 0.04 μ mol/g，但MT缺失小鼠的肝脏锌浓度不变（0.28 +/- 0.04 μ mol/g）。在3周龄时观察到的最突出的组织学异常是MT缺失小鼠肾脏中存在肿胀的Bowman囊。当哺乳期MT无效母鼠喂食严重缺锌（1.5微克/克）饲料时，MT无效幼仔的肾脏发育迟缓，如肾生成区保留和小管发育不完全所示。我们认为，缺乏锌的肝脏水库危及发展中的肾脏在MT-null小鼠。除了对饮食锌限制更敏感外，MT-缺失小鼠对锌毒性更敏感。当成年小鼠用递增剂量的锌激发至总计3700 μ mol锌/kg体重时，MT-无效小鼠与对照小鼠相比具有更高的胰腺腺泡细胞变性发生率，尽管累积较少的锌（对照和MT-无效小鼠分别为2.72 +/- 0.46对1.23 +/- 0.52 μ mol锌/g胰腺，P < 0.05）。这些实验的结果表明，MT I和MT II可以防止锌缺乏和锌毒性。
Metallothionein (MT)-bound zinc accumulates when animals are exposed to excess zinc and is depleted under conditions of zinc deficiency, suggesting that MT serves as a means of sequestering excess zinc as well as a zinc reservoir that can be utilized when zinc is deficient. To examine the importance of MT for these processes, mice with null alleles of both MT I and MT II genes were created and the zinc concentration and histological appearance of multiple organs assessed. At birth, the hepatic zinc concentration of these MT-null mice was lower than that of wild-type controls (0.27 +/- 0.02 vs. 0.65 +/- 0.11 micromol zinc/g tissue, P < 0.05). During the next 3 wk of suckling zinc-replete (95 micrograms zinc/g diet) dams, the hepatic zinc concentration of controls fell to 0.42 +/- 0.04 micromol/g but was unchanged in the MT-null mice (0.28 +/- 0.04 micromol/g). The most prominent histological anomaly observed at 3 wk of age was the presence of swollen Bowman's capsules in the kidneys of MT-null mice. When nursing MT-null dams were fed a severely zinc-deficient (1.5 microg/g) diet, kidney development in the MT-null pups was retarded as indicated by the retention of the nephrogenic zone and incomplete tubule development. We suggest that the lack of a hepatic reservoir of zinc jeopardizes the developing kidney in the MT-null mice. In addition to being more sensitive to dietary zinc restriction, MT-null mice are more sensitive to zinc toxicity. When adult mice were challenged with a ramping dose of zinc up to a total of 3700 micromol zinc/kg body weight, MT-null mice had a greater incidence of pancreatic acinar cell degeneration compared with control mice despite accumulating less zinc (2.72 +/- 0.46 vs. 1.23 +/- 0.52 micromol zinc/g pancreas, control and MT-null, respectively, P < 0.05). The results of these experiments suggest that MT I and MT II can protect against both zinc deficiency and zinc toxicity.