Jacob S T, Ghoshal K, Sheridan J F
Department of Medical Biochemistry, The Ohio State University College of Medicine, Columbus 43210, USA.
Gene Expr. 1999;7(4-6):301-10.
This article describes the effect of restraint stress or social reorganization stress on the induction of metallothionein (MT) in the liver, heart, lung, and spleen. Both MT-I and MT-II mRNA were elevated as much as 30-fold following just 12 h (one cycle) of restraint stress. The amount of MT protein also increased following stress. The MT induction was the highest in the liver, followed by the lung, heart, and spleen. MT-I induction was also observed in the fore, mid, and hind regions of the brain whereas the brain-specific MT-III gene was not activated by stress. The increase in MT mRNA correlated well with the rise in stress-induced serum corticosterone. The induction occurred at the transcriptional level and was mediated essentially by the activation of glucocorticoid receptor. The MT mRNA returned to the control level after nine cycles of stress. Exposure of these habituated mice to a different type of stress (treatment with heavy metals such as cadmium or zinc sulfate) led to further MT induction. Because heavy metals induced MT via activation of the factor MTF-1, distinct molecular mechanisms should be responsible for the activation of MT promoter by different inducers.
本文描述了束缚应激或社会重组应激对肝脏、心脏、肺和脾脏中金属硫蛋白（MT）诱导的影响。仅经过12小时（一个周期）的束缚应激后，MT-I和MT-II mRNA均升高了30倍之多。应激后MT蛋白的量也增加了。MT的诱导在肝脏中最高，其次是肺、心脏和脾脏。在脑的前、中、后区域也观察到MT-I的诱导，而脑特异性MT-III基因未被应激激活。MT mRNA的增加与应激诱导的血清皮质酮的升高密切相关。诱导发生在转录水平，主要由糖皮质激素受体的激活介导。经过九个周期的应激后，MT mRNA恢复到对照水平。将这些适应应激的小鼠暴露于不同类型的应激（用镉或硫酸锌等重金属处理）会导致MT进一步诱导。由于重金属通过激活因子MTF-1诱导MT，不同诱导剂激活MT启动子应有不同的分子机制。
