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Metallothionein (MT) -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury

Citation

Pankhurst, MW and Gell, DA and Butler, CW and Kirkcaldie, MTK and West, AK and Chung, RS, Metallothionein (MT) -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury, Pl o S One, 7, (2) Article e31185. ISSN 1932-6203 (2012) [Refereed Article]


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Licenced under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/

DOI: doi:10.1371/journal.pone.0031185

Abstract

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/II2/2) 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/II2/2 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 upregulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver.

Item Details

Item Type:Refereed Article
Keywords:metallothionein; brain injury; inflammation
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Pankhurst, MW (Mr Michael Pankhurst)
Author:Gell, DA (Dr David Gell)
Author:Butler, CW (Mr Christopher Butler)
Author:Kirkcaldie, MTK (Dr Matthew Kirkcaldie)
Author:West, AK (Professor Adrian West)
Author:Chung, RS (Associate Professor Roger Chung)
ID Code:77576
Year Published:2012
Web of Science® Times Cited:3
Deposited By:Medicine (Discipline)
Deposited On:2012-05-04
Last Modified:2017-10-06
Downloads:195 View Download Statistics

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