METALLOTHIONEIN IN THE LUNG--THE ROLE AS AN ANTIOXIDANT

本项目旨在评估肺金属硫蛋白在肺损伤中的作用， (MTs)作为自由基清除剂和脂质过氧化抑制剂。 我们已经获得了初步的数据，多种干扰素诱导剂， 不仅能抑制肺内高氧脂质过氧化， 高氧大鼠。 我们建议，这种保护与 由于MT含量随干扰素诱导剂增加而增加，因此肺中MT增加 在不同的器官里，可能也在肺里 虽然其他抗氧化剂 也可能增加这些代理，我们没有观察到一个共同的 肺超氧化物歧化酶（SOD）活性升高， 预期这些试剂不会增加过氧化氢酶活性 考察 初步结果还表明，MTs相对 脂质过氧化的强抑制剂，以及有效的羟基 自由基清除剂 我们的第一步是将肺损伤和高氧血症 （大于95%O2）死亡率与肺MT的数量， 将尝试通过各种试剂如干扰素诱导剂 和金属。 其次，我们将估计MT的生物活性，例如 SOD样活性、羟自由基活性与脂质过氧化 抑制活性，在测定MT的每种同种型的含量后， 识别金属种类并量化相关的金属含量 每一种异构体。 我们的第三种方法是从大鼠肺中分离出各种类型的细胞， 测定其MTs含量和高氧敏感性， 调节MT含量。 MT随药物增加的机制 也将试图通过确定周转率来阐明 MTs和通过测量MT mRNA合成速率。 我们预计，执行这些方法后的结果给我们 得出结论的坚实基础MTs作为一个重要的抗氧化剂的作用 以保护肺至少免受高氧损伤。

This project proposes to evaluate the roles of lung metallothioneins (MTs) as free radical scavengers and lipid peroxidation inhibitors. We have obtained preliminary data that multiple interferon inducers not only suppress pulmonary hyperoxic lipid peroxidation but also protect rats from hyperoxia. We propose that this protection is associated with increased MTs in lung since MTs content increase with interferon inducers in various organs and probably in lung, too. Although other antioxidants might also increase with these agents, we did not observe a common increase of pulmonary superoxide dismutase (SOD) activities and the increased catalase activities were not expected with these agents examined. The preliminary results also showed that MTs are relatively strong inhibitors of lipid peroxidation as well as being potent hydroxyl radical scavengers. Our first approach will be to correlate the lung damages and hyperoxic (greater than 95% O2) mortality with the quantity of lung MTs which we will attempt to modulate by various agents such as interferon inducers and metals. Secondly, we will estimate the biological activities of MTs such as SOD-like activity, hydroxyl radical activity and lipid peroxidation inhibition activity, after determining the content of each isoform of MT, identifying metal species and quantifying the metal content associated with each isoform. Our third approach is to isolate various cell types from rat lung and determine their MTs contents and susceptibility to hyperoxia after modulating MTs contents. The mechanism by which MTs increase with agents also will be attempted to elucidate by determining the turnover rate of MTs and by measuring the rate of MT mRNA synthesis. We anticipate that the results after performing these approaches give us the solid basis to conclude the role of MTs as a significant antioxidant in lung to protect at least against hyperoxic damage.