Lu Naihao, Zhang Mingyi, Li Hailing, Gao Zhonghong
Department of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, People's Republic of China.
Chem Res Toxicol. 2008 Jun;21(6):1229-34. doi: 10.1021/tx800013e. Epub 2008 May 7.
Protein tyrosine nitration is becoming increasingly recognized as a prevalent post-translational modification that could serve as a biomarker of nitric oxide (NO)-mediated oxidative stress. One received protein nitration model is the heme- or hemoprotein-dependent pathway that involves the contribution of iron and the formation of free radicals. Therefore, the iron chelating agent desferrioxamine (DFO) can affect the development of oxidative and nitrative stress. In the hemin/nitrite/H2O2 system-induced bovine serum albumin (BSA) nitration and oxidation model, BSA was analyzed for 3-nitrotyosine and carbonyl groups measured by spectrophotometry, SDS-PAGE, and Western blotting upon exposure to DFO. The results showed a significant dose-dependent inhibitory effect of DFO on BSA nitration, while an enhancement on oxidation was surprisingly observed. The promotion on protein oxidation could not be the result of the formation of ferrioxamine since the antinitration and prooxidant effect of DFO was abolished when it combined with Fe3+ to form ferrioxamine. Our studies also indicated that the abnormal effect of DFO on promoting protein oxidation probably originated from the hemin-DFO complex, which needs further study. The completely different effects of DFO on hemin-induced protein tyrosine nitration and protein oxidation should be taken into account when DFO is used in experimental and clinical applications.
蛋白质酪氨酸硝化作为一种普遍的翻译后修饰，越来越被认为可作为一氧化氮（NO）介导的氧化应激的生物标志物。一种公认的蛋白质硝化模型是血红素或血红蛋白依赖性途径，该途径涉及铁的作用和自由基的形成。因此，铁螯合剂去铁胺（DFO）可影响氧化应激和硝化应激的发展。在血红素/亚硝酸盐/H2O2系统诱导的牛血清白蛋白（BSA）硝化和氧化模型中，通过分光光度法、SDS-PAGE和Western印迹法对暴露于DFO后的BSA进行3-硝基酪氨酸和羰基分析。结果显示DFO对BSA硝化具有显著的剂量依赖性抑制作用，而令人惊讶的是观察到对氧化有增强作用。DFO对蛋白质氧化的促进作用不可能是由于形成了铁胺，因为当DFO与Fe3+结合形成铁胺时，其抗硝化和促氧化作用就消失了。我们的研究还表明，DFO促进蛋白质氧化的异常作用可能源于血红素-DFO复合物，这需要进一步研究。在实验和临床应用中使用DFO时，应考虑DFO对血红素诱导的蛋白质酪氨酸硝化和蛋白质氧化的完全不同的影响。
