Zheng H, Berman N E, Klaassen C D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Neurochem Int. 1995 Jul;27(1):43-58. doi: 10.1016/0197-0186(94)00167-s.
Metallothioneins (MTs) are sulfhydryl-rich proteins. MT-I and MT-II are found in all tissues of the body, while MT-III exists only in brain. Regulation of MT-I and MT-III mRNA was studied in brain and liver of control C57BL/6J mice and mice given chemicals known to increase MT-I, namely, lipopolysaccharide (LPS), zinc chloride (Zn), cadmium chloride (Cd), dexamethasone (Dex), ethanol, and kainic acid (KA). Northern blot analysis revealed that MT-I mRNA levels in liver were induced dramatically (12-27-fold over basal levels) by all of the chemicals, while in brain only LPS produced an increase in MT-I mRNA (2-fold). Interestingly, the MT-I inducers, Cd, Dex, ethanol, and KA, down-regulated brain MT-III mRNA levels by approx. 30%. Because brain is such a heterogenous tissue, in situ hybridization was used to localize MT-I and MT-III mRNA in control and treated mice. MT-I mRNA signal, which was most abundant in the glial cells of the Purkinje cell layer of the cerebellum in control mice, appeared to be enhanced in mice given the MT-I inducers (LPS, Zn, Cd, Dex, ethanol, and KA). MT-I mRNA hybridization signal was also enhanced in the olfactory bulbs from LPS- and Cd-treated mice, while this signal was present but weak in control brains. MT-III mRNA hybridization signals were localized in hippocampus and co-localized with MT-I message in the glial cells of the Purkinje cell layer of the cerebellum. In addition, diffuse MT-III mRNA signals were visible in areas of the cerebral cortex, and in the molecular layer of the cerebellum. Signals for MT-III in hippocampus appeared to be reduced by KA, Dex and LPS treatment, while in the cortical region, MT-III mRNA signals appeared to be enhanced by KA, Cd, and ethanol treatment. In conclusion, both MT-I and MT-III expression in brain appears to be modulated by exogenous treatment, however, the changes are small in relation to those observed in liver. Chemical-induced alterations of MT mRNA are non-uniform throughout the brain, and thus best studied in a region-specific manner.
金属硫蛋白（MTs）是富含巯基的蛋白质。MT-I和MT-II存在于身体的所有组织中，而MT-III仅存在于大脑中。研究了对照C57BL/6J小鼠以及给予已知可增加MT-I的化学物质（即脂多糖（LPS）、氯化锌（Zn）、氯化镉（Cd）、地塞米松（Dex）、乙醇和 kainic 酸（KA））的小鼠的大脑和肝脏中MT-I和MT-III mRNA的调节情况。Northern印迹分析显示，所有化学物质均显著诱导肝脏中MT-I mRNA水平（比基础水平高12 - 27倍），而在大脑中只有LPS使MT-I mRNA增加（2倍）。有趣的是，MT-I诱导剂Cd、Dex、乙醇和KA使大脑MT-III mRNA水平下调约30%。由于大脑是如此异质性的组织，因此使用原位杂交来定位对照小鼠和处理后小鼠中的MT-I和MT-III mRNA。MT-I mRNA信号在对照小鼠小脑浦肯野细胞层的神经胶质细胞中最为丰富，在给予MT-I诱导剂（LPS、Zn、Cd、Dex、乙醇和KA）的小鼠中似乎增强。来自LPS和Cd处理小鼠的嗅球中MT-I mRNA杂交信号也增强，而在对照大脑中该信号存在但较弱。MT-III mRNA杂交信号定位于海马体，并与小脑浦肯野细胞层神经胶质细胞中的MT-I信号共定位。此外，在大脑皮层区域以及小脑分子层中可见弥漫性的MT-III mRNA信号。海马体中MT-III的信号似乎因KA、Dex和LPS处理而减少，而在皮层区域，MT-III mRNA信号似乎因KA、Cd和乙醇处理而增强。总之，大脑中MT-I和MT-III的表达似乎都受到外源处理的调节，然而，与在肝脏中观察到的变化相比，这些变化较小。化学诱导的MT mRNA改变在整个大脑中并不均匀，因此最好以区域特异性方式进行研究。
