title: Metallothionein (MT) -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury.
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/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.
  
  
  CONCLUSIONS
  MT-I/II is up-regulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia. michael.pankhurst@anatomy.otago.ac.nz
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pankhurst
authors.forename: David A
authors.initials: DA
authors.lastname: Gell
authors.forename: Chris W
authors.initials: CW
authors.lastname: Butler
authors.forename: Matthew T K
authors.initials: MT
authors.lastname: Kirkcaldie
authors.forename: Adrian K
authors.initials: AK
authors.lastname: West
authors.forename: Roger S
authors.initials: RS
authors.lastname: Chung
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000097:blood / Q000235:genetics / Q000473:pathology*; D003080:Cold Temperature; D003345:Corticosterone / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016015:Logistic Models; D008668:Metallothionein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D012015:Reference Standards; D015203:Reproducibility of Results; D013054:Spectrophotometry, Atomic; D014020:Tissue Extracts; D015032:Zinc / Q000378:metabolism*
chemical_list: D000906:Antibodies; C491054:Mt2 protein, mouse; D012333:RNA, Messenger; D014020:Tissue Extracts; C525355:metallothionein-1, mouse; D008668:Metallothionein; D015032:Zinc; D003345:Corticosterone