NUCLEAR ZINC UPTAKE AND INTERACTIONS AND METALLOTHIONEIN GENE-EXPRESSION ARE INFLUENCED BY DIETARY ZINC IN RATS
NUCLEAR ZINC UPTAKE AND INTERACTIONS AND METALLOTHIONEIN GENE-EXPRESSION ARE INFLUENCED BY DIETARY ZINC IN RATS
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DOI：
10.1093/jn/122.1.56
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发表时间：
1992-01-01
影响因子：
4.2
通讯作者：
LEEAMBROSE, LM
中科院分区：
文献类型：
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作者：
COUSINS, RJ;LEEAMBROSE, LM
在生长期大鼠中研究了膳食锌对金属硫蛋白基因表达的调节以及膳食锌与核锌摄取的关系。以5、30或180 mg/kg的剂量饲喂锌，以颗粒形式饲喂2周（自由采食）或以液化制剂形式饲喂2小时（1 g/4 mL）。口服剂量后两小时，肠道和肝脏比其他组织吸收更多的锌。从肝脏、肾脏和脾脏中提取的细胞核在2小时的饲养期内积累了大量的锌，并直接反映了饲料中锌的水平。肾脏细胞核在2 h内积累的锌量最大，占总细胞核锌浓度的6.2%。北方分析表明，金属硫蛋白的表达在某些组织中与膳食锌摄入量成正比。在肾脏中的含量最高，依次为肝、肠、脾、心。胸腺和肺金属硫蛋白mRNA水平没有明显改变饮食锌摄入量。肝细胞核提取物的色谱分析表明，Zn-65引入到门静脉供应结合到核蛋白的离散部分。这些馏分结合Zn-65和P-32标记的寡核苷酸对应的金属硫蛋白启动子的金属调控元件。这些结果表明，饮食中大量的锌被细胞核迅速吸收。此外，他们认为，金属硫蛋白基因和其他基因与金属调控元件的转录调控涉及饮食供应和结合锌的核内因子之间的直接相互作用。
Regulation of metallothionein gene expression by dietary zinc and the relationship of dietary zinc to nuclear zinc uptake was examined in growing rats. Zinc was fed at 5, 30 or 180 mg/kg, either in pelleted form for a 2-wk period (ad libitum) or for 2 h as a liquefied preparation (1 g in 4 mL). Two hours after the oral dose, the intestine and liver took up more zinc than other tissues. Nuclei purified from liver, kidney and spleen accumulated substantial amounts of zinc and directly reflected the dietary zinc level within the 2-h feeding period. Nuclei from kidney accumulated the largest amount of dietary zinc within 2 h, accounting for up to 6.2% of the total nuclear zinc concentration. Northern analysis demonstrated that metallothionein expression was proportional to dietary zinc intake in some tissues. It was greatest in kidney, followed in descending order by liver, intestine, spleen and heart. Thymus and lung metallothionein mRNA levels were not changed appreciably by dietary zinc intake. Chromatography of extracts from liver nuclei shows that Zn-65 introduced into the portal supply is bound to discrete fractions of nuclear proteins. One of these fractions binds both Zn-65 and a P-32-labeled oligonucleotide corresponding to the metal regulatory element of the metallothionein promoter. These results demonstrate that significant amounts of zinc from the diet are rapidly taken up by cell nuclei. Furthermore, they suggest that transcriptional regulation of the metallothionein gene and other genes with metal regulatory elements involves a direct interaction between the dietary supply and intranuclear factors that bind zinc.