The biogenic methanobactin is an effective chelator for copper in a rat model for Wilson disease.
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| Abstract |
Copper is an essential redox-active metal ion which in excess becomes toxic due to the formation of reactive oxygen species. In Wilson disease the elevated copper level in liver leads to chronic oxidative stress and subsequent hepatitis. This study was designed to evaluate the copper chelating efficiency of the bacterial methanobactin (MB) in a rat model for Wilson disease. Methanobactin is a small peptide produced by the methanotrophic bacterium Methylosinus trichosporium OB3b and has an extremely high affinity for copper. Methanobactin treatment of the rats was started at high liver copper and serum aspartate aminotransferase (AST) levels. Two dosing schedules with either 6 or 13 intraperitoneal doses of 200mg methanobactin per kg body weight were applied. Methanobactin treatment led to a return of serum AST values to basal levels and a normalization of liver histopathology. Concomitantly, copper levels declined to 45% and 24% of untreated animals after 6 and 13 doses, respectively. Intravenous application of methanobactin led to a prompt release of copper from liver into bile and the copper was shown to be associated with methanobactin. In vitro experiments with liver cytosol high in copper metallothionein demonstrated that methanobactin removes copper from metallothionein confirming the potent copper chelating activity of methanobactin.
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| Authors | Karl H Summer, Josef Lichtmannegger, Nathan Bandow, Don W Choi, Alan A DiSpirito, Bernhard Michalke |
| Journal | Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (J Trace Elem Med Biol) Vol. 25 Issue 1 Pg. 36-41 (Jan 2011) ISSN: 1878-3252 [Electronic] Germany |
| PMID | 21242075 (Publication Type: Journal Article) |
| Copyright | Copyright © 2010 Elsevier GmbH. All rights reserved. |
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