Andrews G K, Gallant K R, Cherian M G
Eur J Biochem. 1987 Aug 3;166(3):527-31. doi: 10.1111/j.1432-1033.1987.tb13545.x.
To investigate the role of metals in the regulation of the ontogenic expression of rat liver metallothionein (MT) mRNA, the concentrations of zinc, MT and MT mRNA were determined in livers of fetal and newborn rats from dams which were fed with a control or zinc-deficient or copper-deficient or iron-deficient diet from day 12 of gestation. The liver samples were analyzed for MT-mRNA levels using a mouse MT-I cRNA probe. Although the newborn hepatic levels of each metal (zinc or copper or iron) was specifically reduced corresponding to the respective mineral deficiencies, the hepatic concentrations of total MT and MT-I mRNA were significantly decreased only in pups born from zinc-deficient dams. Injection of the zinc-deficient newborn pups with 20 mg Zn as ZnSO4/kg restored with MT-I mRNA levels to slightly above control values within 5 h of injection. The hepatic zinc, MT and MT-I mRNA levels were observed to increase significantly in control fetal rat liver on days 17-21 of gestation but there were little changes in either zinc or MT in fetal livers from zinc-deficient dams during the late gestational period. The MT-I mRNA level also did not show an increase on days 18 and 20 of gestation in zinc-deficient fetal liver as compared to controls. These results demonstrate a direct role of zinc in hepatic MT gene expression in rat liver during late gestation. Immunohistochemical localization of MT using a specific antibody to rat liver MT showed that the staining for MT in zinc-deficient pup liver was mainly in the cytosol in contrast to the significant nuclear MT staining observed in control newborn rat liver. The results suggest that maternal zinc deficiency has a marked effect not only in decreasing the levels of hepatic MT and MT-I mRNA but also in the localization of MT in newborn rat liver.
为了研究金属在大鼠肝脏金属硫蛋白（MT）mRNA个体发育表达调控中的作用，测定了妊娠第12天起喂食对照、缺锌、缺铜或缺铁饮食的母鼠所产新生和胎鼠肝脏中的锌、MT和MT mRNA浓度。使用小鼠MT-I cRNA探针分析肝脏样本中的MT-mRNA水平。尽管每种金属（锌、铜或铁）的新生肝脏水平因各自的矿物质缺乏而特异性降低，但仅在缺锌母鼠所产幼崽中，肝脏总MT和MT-I mRNA浓度显著降低。给缺锌的新生幼崽注射20 mg ZnSO₄/kg的锌，在注射后5小时内MT-I mRNA水平恢复到略高于对照值。观察到对照胎鼠肝脏在妊娠第17 - 21天肝脏锌、MT和MT-I mRNA水平显著升高，但在妊娠后期，缺锌母鼠的胎鼠肝脏中锌或MT几乎没有变化。与对照组相比，缺锌胎鼠肝脏在妊娠第18天和20天MT-I mRNA水平也未升高。这些结果表明锌在妊娠后期大鼠肝脏MT基因表达中起直接作用。使用针对大鼠肝脏MT的特异性抗体对MT进行免疫组织化学定位显示，缺锌幼崽肝脏中MT的染色主要在细胞质中，而对照新生大鼠肝脏中观察到显著的细胞核MT染色。结果表明，母体缺锌不仅对降低肝脏MT和MT-I mRNA水平有显著影响，而且对新生大鼠肝脏中MT的定位也有显著影响。
