Alterations in the levels of metallothionein and metals in the liver, and unique serum liver enzyme response in metallothionein knock-out mice after burn injury.
OBJECTIVE
Metallothionein (MT) is a small cysteine-rich protein that sequesters and distributes metal ions. Its overexpression stimulates cell proliferation and inhibits apoptosis. We investigated the effects of burn injury on MT expression and metal localization. We also sought to determine roles of MT in the pathophysiologic alterations in the liver after injury.


METHODS
Mice (C57BLKS/J, MT-I/II knock-out, KO, and wild-type control mice) were subjected to an 18% burn. Liver tissues harvested after injury were analyzed for the MT expression and the levels of zinc, copper, manganese, and iron. Levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were measured in serum samples from MT-I/MT-II KO mice and controls after injury.


RESULTS
Transient induction of MT-I and MT-II mRNAs was observed 3-6 h after injury, while MT-I/MT-II protein peaked on day 1. The induction was localized to hepatocytic nuclei. The intrahepatic levels of zinc, copper, and iron were transiently elevated on day 1, when a downregulation of manganese was evident. Interestingly, only the serum levels of aspartate aminotransferase were significantly augmented in MT-I/MT-II KO mice compared to controls after injury.


CONCLUSIONS
These data suggest that MT and metals may participate in the pathogenesis of the liver after burn injury.
Cho
Kiho
K
Burn Research, Shriners Hospitals for Children Northern California, Sacramento, CA 95817, USA.
Adamson
Lee
L
Jeong
Jayoung
J
VanHook
Tajia
T
Rucker
Robert
R
Greenhalgh
David
D
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002056:Burns / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004798:Enzymes / Q000097:blood*; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008668:Metallothionein / Q000378:metabolism*; D019216:Metals, Heavy / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis
D004798:Enzymes; D019216:Metals, Heavy; D012333:RNA, Messenger; D008668:Metallothionein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase