METALLOTHIONEIN IN THE LUNG--THE ROLE AS AN ANTIOXIDANT

肺中的金属硫蛋白——作为抗氧化剂的作用

• 批准号: 5211960
• 负责人: SUMIO YANO
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5211960
• 关键词: RNA biosynthesis; animal mortality; antioxidants; cell type; cytotoxicity; free radical scavengers; hydroxyl radical; interferon inducers; isozymes; laboratory rabbit; laboratory rat; lipid peroxides; lung; metallothionein; oxygen tension; radioimmunoassay; tissue /cell culture

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.

该项目旨在评估肺金属硫蛋白的作用 （MT）作为自由基清除剂和脂质过氧化抑制剂。 我们已经获得初步数据，多种干扰素诱导剂不会 不仅抑制肺部高氧脂质过氧化作用，而且还具有保护作用 大鼠因高氧。 我们建议这种保护与 由于干扰素诱导剂导致 MT 含量增加，因此肺部 MT 增加 在各种器官中，也可能在肺中。 虽然其他抗氧化剂 这些药物也可能会增加，但我们没有观察到常见的 肺超氧化物歧化酶（SOD）活性增加 这些药物不会增加过氧化氢酶活性 检查了。 初步结果还表明，MT 相对 脂质过氧化的强抑制剂以及有效的羟基 激进的清道夫。 我们的第一个方法是将肺损伤和高氧相关联 （大于 95% O2）死亡率与肺 MT 数量的关系 将尝试通过干扰素诱导剂等各种药物进行调节 和金属。 其次，我们将估计 MT 的生物活性，例如 SOD 样活性、羟自由基活性和脂质过氧化 抑制活性，测定MT各亚型的含量后， 识别金属种类并量化相关金属含量 与每个亚型。 我们的第三种方法是从大鼠肺中分离出各种细胞类型 测定其 MTs 含量和对高氧的敏感性 调节 MT 内容。 MT随代理增加的机制 还将尝试通过确定周转率来阐明 MT 并通过测量 MT mRNA 合成率。 我们预计执行这些方法后的结果会给我们带来 为总结 MT 作为重要抗氧化剂的作用奠定了坚实的基础 在肺部至少可以防止高氧损伤。