侯玮钰，张 丹，朱琼妮，徐尚福，吴 芹，陆远富，刘 杰,2

    (1.遵义医学院 基础药理省部共建教育部重点实验室，贵州 遵义 563099 ； 2.University of Kansas Medical Center, Kansas City, KS 66160, USA)

    1 Introduction

    Metallothionein (MT) is a low-molecular-weight, cysteine-rich, metal-binding protein.MT genes are readily induced by various physiological and toxicological stimuli. MT is rich in cysteine residues, and plays important roles in the detoxification of heavy metals, in the homeostasis of essential metals, and in the scavenge of free radicals[1].There are four isoforms of MT in rodents, MT-1 and MT-2 are major isoforms in the liver and coordinately regulated[1].MT-3 mainly locates in brain and MT-4 in squamous tissues such as tong[1-2].MT is proposed to have a variety of biological functions, and implicated in liver diseases, ageing, and carcinogenesis[1-4].

    Induction of MT protects against acute liver injury produced by cadmium, carbon tetrachloride, acetaminophen, and other toxicants[1-2].In chronic hepatitis C patients, hepatic MT levels are associated with the severity of HCV infection, and are linked to a better response to interferon therapy[3].MT gene therapy leads to resolution of liver fibrosis in mice[4], possibly by the inhibition of activated HSCs and increases in collagenases[5].Zinc deficiencies are observed in many types of liver disease, including alcoholic liver disease and viral liver diseases and MT is proposed to play important roles in maintaining zinc homeostasis. In addition, zinc therapy has replaced penicillamine as the first-line therapy for Wilson's disease, probably through induction of MT to sequester copper[6].Thus, liver is a major target of MT therapy[1-4]. ......