Sensitivity of metallothionein-null mice to LPS/D-galactosamine-induced lethality

Mice treated with lipopolysaccharide (LPS)/D-galactosamine (GalN) selectively develop hepatic failure. The acute-phase protein alpha(1)-acid glycoprotein (AGP) has been demonstrated to protect mice from LPS/GalN-induced lethality. Metallothionein (MT), which is a low-molecular weight, cysteine-rich,...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-01, Vol.280 (1), p.358
Main Authors: Kimura, T, Itoh, N, Takehara, M, Oguro, I, Ishizaki, J I, Nakanishi, T, Tanaka, K
Format: Article
Language:English
Subjects:
Animals
Chemical and Drug Induced Liver Injury - blood
Chemical and Drug Induced Liver Injury - genetics
Chemical and Drug Induced Liver Injury - physiopathology
Death
Escherichia coli
Galactosamine - toxicity
Gene Expression Regulation - drug effects
Lipopolysaccharides - toxicity
Male
Metallothionein - deficiency
Metallothionein - genetics
Metallothionein - physiology
Mice
Mice, Inbred Strains
Mice, Knockout
Nitrogen Oxides - blood
Orosomucoid - genetics
RNA, Messenger - genetics
Transcription, Genetic - drug effects
Tumor Necrosis Factor-alpha - analysis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mice treated with lipopolysaccharide (LPS)/D-galactosamine (GalN) selectively develop hepatic failure. The acute-phase protein alpha(1)-acid glycoprotein (AGP) has been demonstrated to protect mice from LPS/GalN-induced lethality. Metallothionein (MT), which is a low-molecular weight, cysteine-rich, metal-binding protein, is also induced in the acute-phase reaction. However, the specific function of MT in acute-phase response remain to be elucidated. We showed that MT-null mice were more sensitive to LPS/GalN-induced lethality than wild-type mice. The increase in vital mediator levels, TNF-alpha and NO were of similar levels in wild-type and MT-null mice. A remarkable increase in plasma platelet-activating factor levels was not observed in our experimental conditions. On the other hands, the mRNA level of AGP in the response to LPS/GalN was decreased in MT-null mice compared to wild-type mice. These results indicated that MT may have the potential to prevent LPS/GalN-induced lethality, at least through the attenuation of AGP induction.
ISSN:0006-291X
DOI:10.1006/bbrc.2000.4085