Coordinate regulation of zinc metabolism and metallothionein gene expression in rats.
Coordinate regulation of zinc metabolism and metallothionein gene expression in rats.
复制标题
协调调节大鼠锌代谢和金属硫蛋白基因表达。
DOI：
10.1152/ajpendo.1986.251.6.e688
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
DiSilvestro,RA
中科院分区：
文献类型：
--
作者：
Cousins,RJ;Dunn,MA;Leinart,AS;Yedinak,KC;DiSilvestro,RA
在喂饲足量锌的大鼠中检查了双丁酰cAMP、胰高血糖素和肾上腺素对锌代谢的调节。双丁酰cAMP、肾上腺素和胰高血糖素在首次给药后10小时分别使肝脏金属硫蛋白水平升高。肝脏金属硫蛋白的增加与血清锌浓度呈负相关。地塞米松，糖皮质激素治疗，加重这些影响在一定程度上。双丁酰cAMP和胰高血糖素均可诱导金属硫蛋白I和II。使用与金属硫蛋白I和II基因的5'区互补的合成的21-碱基寡核苷酸，通过斑点杂交测量总肝RNA提取物中金属硫蛋白mRNA的水平。单独给予二丁酰cAMP、胰高血糖素和肾上腺素可使每个细胞的金属硫蛋白mRNA分子数量增加4倍。这些数据表明，胰高血糖素和肾上腺素是金属硫蛋白基因表达的主要调节剂，至少部分通过cAMP起作用。在肾上腺切除大鼠中，胰高血糖素、二丁酰cAMP和肾上腺素在金属硫蛋白诱导和血清锌浓度抑制方面的作用较弱。当同时给予地塞米松时，这些效果在很大程度上得到恢复。总的来说，这些数据表明，锌代谢的变化与急性应激涉及协调调节介导的许多因素，包括糖皮质激素和cAMP。
Regulation of zinc metabolism by dibutyryl cAMP, glucagon, and epinephrine was examined in rats fed adequate amounts of zinc. Dibutyryl cAMP, epinephrine, and glucagon each produced an increase in liver metallothionein levels by 10 h after they were first administered. The increase in liver metallothionein was inversely related to the serum zinc concentration. Treatment with dexamethasone, a glucocorticoid, accentuated these effects to some extent. Both metallothionein I and II were induced by dibutyryl cAMP and glucagon. Levels of metallothionein mRNA in total liver RNA extracts were measured by dot blot hybridization using a synthetic 21-base oligonucleotide complimentary to the 5' region of both the metallothionein I and II genes. Individual administration of dibutyryl cAMP, glucagon, and epinephrine increased the number of metallothionein mRNA molecules per cell by up to fourfold. The data suggest that glucagon and epinephrine are primary regulators of metallothionein gene expression acting at least in part via cAMP. In adrenalectomized rats, glucagon, dibutyryl cAMP, and epinephrine had a less potent effect in terms of metallothionein induction and depression of serum zinc concentrations. These effects were largely restored when dexamethasone was also given. Collectively these data suggest that changes in zinc metabolism associated with acute stress involve coordinate regulation mediated by many factors, including glucocorticoids and cAMP.