Kang Y J
Department of Medicine, Pharmacology and Toxiciology, University of Louisville School of Medicine, Kentucky 40292, USA.
Proc Soc Exp Biol Med. 1999 Dec;222(3):263-73. doi: 10.1046/j.1525-1373.1999.d01-143.x.
The antioxidant function of metallothionein (MT) was first suggested in the early 1980s. Studies in vitro have revealed that MT reacts directly with reactive oxygen species, including superoxide and hydroxyl radicals and hydrogen peroxide. These reactions have never been demonstrated in intact animal studies. Nevertheless, both pharmacologic and genetic studies have shown that MT functions in protection against oxidative injury in vivo. In particular, the antioxidant function of MT in the heart has been explored extensively. The data gathered from recent studies using a cardiac-specific, MT-overexpressing transgenic mouse model have provided direct evidence to support this physiological role of MT. Under acute and chronic oxidative stress conditions such as treatment with doxorubicin, ischemia-reperfusion, and dietary copper restriction, MT-overexpressing transgenic mouse hearts displayed a marked resistance to the injurious consequences, including biochemical, pathological, and functional alterations. This protective action of MT correlates with its inhibition of reactive oxygen species-induced lipid peroxidation. A critical elucidation of the mechanism of action of MT as an antioxidant in vivo remains to be achieved. However, the combination of recent understanding of the zinc cluster structure of MT and novel molecular genetic approaches has provided the basis for further advancement in this field.
金属硫蛋白（MT）的抗氧化功能最早在20世纪80年代初被提出。体外研究表明，MT可直接与活性氧反应，包括超氧阴离子、羟自由基和过氧化氢。这些反应在完整动物研究中从未得到证实。然而，药理学和遗传学研究均表明，MT在体内具有保护机体免受氧化损伤的功能。特别是，MT在心脏中的抗氧化功能已得到广泛研究。最近利用心脏特异性、MT过表达转基因小鼠模型所收集的数据，为支持MT的这一生理作用提供了直接证据。在急性和慢性氧化应激条件下，如用阿霉素处理、缺血再灌注和饮食中铜限制，MT过表达转基因小鼠心脏对包括生化、病理和功能改变在内的有害后果表现出显著抗性。MT的这种保护作用与其对活性氧诱导的脂质过氧化的抑制作用相关。MT作为体内抗氧化剂的作用机制仍有待深入阐明。然而，最近对MT锌簇结构的认识与新型分子遗传学方法的结合，为该领域的进一步发展提供了基础。
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