Metallothionein (MT) -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury.
Metallothionein (MT) -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury.
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DOI：
10.1371/journal.pone.0031185
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chung RS
中科院分区：
文献类型：
--
作者：
Pankhurst MW;Gell DA;Butler CW;Kirkcaldie MT;West AK;Chung RS
对转基因过表达和零突变小鼠的实验表明，金属硫蛋白- i和-II （MT-I/II）在脑损伤后具有保护作用。MT-I/II主要是一种锌结合蛋白，目前尚不清楚它是如何为受伤的大脑提供神经保护的，也不知道MT-I/II在哪里起作用。MT-I/II通常在应激条件下在肝脏中表达，但迄今为止，脑损伤后MT-I/II表达的测量主要集中在受伤的大脑本身。本研究采用定量逆转录酶PCR （RT-PCR）和酶联免疫吸附法（ELISA）结合UC1MT抗体检测小鼠冻裂脑损伤后肝脏中MT-I/II的表达。利用MT-I/II敲除（MT-I/II−/−）小鼠组织构建位移曲线来验证ELISA。肝脏MT-I和MT-II mRNA水平在脑损伤24小时内显著升高，但肝脏MT-I/II蛋白水平直到损伤后3天（DPI）才显著升高，并在实验结束时（7 DPI）达到峰值。用原子吸收光谱法测定肝脏锌含量，发现在1和3 DPI时下降，但在7DPI时恢复正常。MT-I/II−/−小鼠肝脏中的锌在7 DPI时没有恢复正常，这表明脑损伤后，MT-I/II负责将升高的锌水平隔离到肝脏。结论：脑损伤后肝脏中MT-I/II表达上调，并调节肝脏中锌的固存量。
Experiments with transgenic over-expressing, and null mutant mice have determined that metallothionein-I and -II (MT-I/II) are protective after brain injury. MT-I/II is primarily a zinc-binding protein and it is not known how it provides neuroprotection to the injured brain or where MT-I/II acts to have its effects. MT-I/II is often expressed in the liver under stressful conditions but to date, measurement of MT-I/II expression after brain injury has focused primarily on the injured brain itself. In the present study we measured MT-I/II expression in the liver of mice after cryolesion brain injury by quantitative reverse-transcriptase PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) with the UC1MT antibody. Displacement curves constructed using MT-I/II knockout (MT-I/II−/−) mouse tissues were used to validate the ELISA. Hepatic MT-I and MT-II mRNA levels were significantly increased within 24 hours of brain injury but hepatic MT-I/II protein levels were not significantly increased until 3 days post injury (DPI) and were maximal at the end of the experimental period, 7 DPI. Hepatic zinc content was measured by atomic absorption spectroscopy and was found to decrease at 1 and 3 DPI but returned to normal by 7DPI. Zinc in the livers of MT-I/II−/− mice did not show a return to normal at 7 DPI which suggests that after brain injury, MT-I/II is responsible for sequestering elevated levels of zinc to the liver. Conclusion: MT-I/II is up-regulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver.
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影响因子：
4.5
作者：
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