The biogenic methanobactin is an effective chelator for copper in a rat model for Wilson disease.
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.
Institute of Toxicology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Karl H
KH
Summer
Josef
J
Lichtmannegger
Nathan
N
Bandow
Don W
DW
Choi
Alan A
AA
DiSpirito
Bernhard
B
Michalke
D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D006527:Hepatolenticular Degeneration / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
D002614:Chelating Agents; D007093:Imidazoles; D009842:Oligopeptides; C491147:methanobactin