Lu Naihao, He Yingjie, Chen Chao, Tian Rong, Xiao Qiang, Peng Yi-Yuan
Jiangxi Key Laboratory of Functional Organic Molecules, Jiangxi Science and Technology Normal University, Nanchang 330013, China; Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
Toxicol In Vitro. 2014 Aug;28(5):847-55. doi: 10.1016/j.tiv.2014.03.014. Epub 2014 Apr 1.
The toxic mechanism of hemoglobin (Hb) under oxidative stress is linked to the formations of highly cytotoxic ferryl species and subsequently heme-to-protein cross-linked derivative of Hb (Hb-X). In this study, we have examined the effects of free tyrosine and its analogues (3-chlorotyrosine, phenylalanine) on the stability of ferryl hemoglobin and the formation of Hb-X. The results showed that free tyrosine (not phenylalanine, 10-500 μM) was an efficient reducing agent of ferryl species and also effective at preventing the formation of cytotoxic Hb-X. Meanwhile, the dimeric tyrosine was formed as the oxidation product of tyrosine during Hb redox reaction. Compared with free tyrosine, 3-chlorotyrosine, an oxidation product of tyrosine and a proposed biomarker for hypochlorous acid (HOCl) in vivo, exhibited stronger antioxidant properties in Hb-induced oxidative stress, which was consistent with its more efficient ability in the reduction of ferryl species. These results showed that the presence of tyrosine and its derivative in vivo and vitro could ameliorate oxidative damage through ferryl heme reduction. The antioxidant ability, therefore, may provide new insights into the nutritional and physiological significance of free tyrosine with redox active heme proteins-related oxidative stress.
血红蛋白（Hb）在氧化应激下的毒性机制与高细胞毒性的高铁血红素物种的形成以及随后血红蛋白的血红素与蛋白质交联衍生物（Hb-X）的形成有关。在本研究中，我们研究了游离酪氨酸及其类似物（3-氯酪氨酸、苯丙氨酸）对高铁血红蛋白稳定性和Hb-X形成的影响。结果表明，游离酪氨酸（而非苯丙氨酸，10 - 500 μM）是高铁血红素物种的有效还原剂，并且在防止细胞毒性Hb-X的形成方面也有效。同时，二聚体酪氨酸是酪氨酸在Hb氧化还原反应过程中的氧化产物。与游离酪氨酸相比，3-氯酪氨酸是酪氨酸的氧化产物，也是体内次氯酸（HOCl）的一种假定生物标志物，在Hb诱导的氧化应激中表现出更强的抗氧化特性，这与其还原高铁血红素物种的能力更强是一致的。这些结果表明，酪氨酸及其衍生物在体内和体外的存在可通过还原高铁血红素减轻氧化损伤。因此，这种抗氧化能力可能为游离酪氨酸与氧化还原活性血红素蛋白相关氧化应激的营养和生理意义提供新的见解。
