NITROXIDE METABOLISM IN ADENOVIRUS TRANSFORMED CELLS

腺病毒转化细胞中的氮氧化物代谢

• 批准号: 6120611
• 负责人: PHILIP D MORSE
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-15 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120611
• 关键词: animal tissue; biomedical resource; drug adverse effect

Krishna et al (Proc. Natl. Acad. Sci. USA 89:5537-5541, 1992) showed that nitroxides act as superoxide disumate (SOD) mimetics but are oxidized to the oxoammonium instead of reduced to the hydroxylamine (as they previously stated, Samuni et al (J. Biol. Chem. 263:17921-17924, 1988). Our data supports their more recent conclusions. In our mechanism, TEMPOL is reduced by two mechanisms, 1) by one electron reduction via the electron transport system and 2) by two electron reduction from the oxoammonium ion produced by SOD-like activity of the nitroxide. Peroxide re-oxidizes the hydroxylamine to the nitroxide and plays a major role in determining overall nitroxide reduction rates. Catalase activity in the 983.2 cells is only 5% of that in the BHK cells which may allow excess peroxide to recycle the hydroxylamine back to the nitroxide. This would explain the lower overall TEMPOL reduction rates seen in 983.2 cells compared to BHK cells. Our model and the evidence in support of it was presen ted in detail during 1995, and some further progress was made in 1996 and 1997. Supported by NIH grants R15 GM 44365-01 to PDM and R15 CA52091-01A1 to LAL.

Krishna等人（Proc. Natl. Acad. Sci. USA 89：5537-5541，1992） 表明，氮氧化物作为超氧化物歧化酶（SOD）模拟物，但 被氧化成氧代铵，而不是被还原成 羟胺（如他们先前所述，Samuni等人（J. Biol. Chem. 263：17921-17924，1988）。 我们的数据支持他们最近的 结论. 在我们的机制中，TEMPO通过两种机制减少， 1)通过经由电子传输系统的一个电子还原，和2） 通过两个电子还原产生的氧铵离子， 氮氧自由基的SOD样活性。 过氧化氢再氧化 羟胺的氮氧自由基，并发挥了主要作用，在确定 总氮氧化物还原速率。 过氧化氢酶活性983.2 细胞中的浓度仅为BHK细胞中的5%，这可能允许过量的 过氧化物以将羟胺再循环回到氮氧化物。 这 这可以解释983.2中TEMPOL总体减少率较低的原因。 与BHK细胞相比。 我们的模型和证据支持 1995年期间详细介绍了该计划， 在1996年和1997年。 由NIH赠款R15 GM 44365-01给PDM 和R15 CA 52091 - 01 A1至LAL。