Metallothionein-Null Mice Are Sensitive to Endotoxine/D-Galactosamine-Induced Hepatotoxicity.

Abstract

Metallothionein (MT), which is a low-molecular weight, cysteine-rich, metal-binding protein, is induced during acute-phase reactions. However, the specific function of MT in the acute-phase response remains to be elucidated. We previously reported that MT-I, II deficient (MT-null) mice are highly sensitive to the lethal effects of lipopolysaccharide (LPS)/D-galactosamine (GalN). We designed the present study to clarify the major cause of the differences in the sensitivity to the lethal effects of LPS/GalN between wild type and MT-null mice. We found that histological grade of hepatocellular necrosis, induced by LPS/GalN, was greater in MT-null mice than in wild type mice. Therefore, the present findings suggest that MT induction has the potential as an attenuator of LPS/GalNinduced liver necrosis.

Metal Response Element-binding Transcription Factor-1 Is Activated by Degradation of Metallothionein

“…It is known that MT-KO mice are hypersensitive to lipopolysaccharide (LPS)-induced coagulatory disturbance 23) and LPS/D-galactosamine-induced lethality. 24,25) It is possible that this hypersensitivity is related to a lack of MT-mediated MTF-1 activation.…”

MRP5b/SMRP mRNA is Highly Expressed in Metallothionein- Deficient Mouse Liver

“…Metallothionein (MT) is a small protein that plays a role in protecting against the toxic effects of heavy metals and xenobiotics as well as in drug resistance and free radical scavenging, [1][2][3][4] and MT knockout mice exhibit hypersensitivity to heavy metals, such as a cadmium 5,6) and mercury. 7) MT is known to be one of the factors involved in resistance to cisplatin, and Sato et al reported that MT knockout mice are more sensitive to cisplatin than normal mice.…”