BIOLOGICAL CONSEQUENCES OF PROTEIN OXIDATION

蛋白质可以在体外多种条件下被氧化， in vivo. 特异性多肽变化包括醛的形成 （羰基）基团，甲硫氨酸亚砜和二酪氨酸的产生， 二硫键重排、肽键断裂和蛋白质 聚合来 蛋白质氧化修饰的后果是 各种各样。 一些修改导致不同的磁化率的一个 蛋白质的蛋白水解裂解，而其他引起的增益或损失， 生物活性 例如，我们已经发现， 纤维蛋白原的修饰抑制了蛋白质经历 凝血 相反，血浆蛋白酶抑制剂的氧化可导致 凝血活性的增加。 我们的研究旨在 阐明蛋白质获得氧化的条件 修改，并确保所采用的测定提供正确的 评估发生的修改类型。 在最近完成的 实验中，我们确定，碳水化合物部分的 糖蛋白不经历氧化修饰成羰基 在氧化氨基酸侧链的条件下。 另外我们 验证了蛋白质羰基的蛋白质印迹测定法的使用， 对糖蛋白的影响 目前的研究旨在确定 蛋白质在细胞内发生氧化修饰， 不同的生长条件，包括氧化应激。 因为蜂窝 脂质也是氧化攻击的目标， 通过共轭反应，区分 脂质衍生的蛋白质修饰和直接蛋白质氧化 改性 目前正在开发实现这一点的测定法。

Proteins can become oxidized under a variety of conditions in vitro and in vivo. Specific polypeptide changes include formation of aldehyde (carbonyl) groups, generation of methionine sulfoxide and dityrosine, rearrangement of disulfide bonds, cleavage of peptide bonds, and protein aggregation. The consequences of protein oxidative modifications are varied. Some modifications lead to differential susceptibility of a protein to proteolytic cleavage while others cause gain or loss of biological activity. For example, we have found that oxidative modification of fibrinogen inhibits ability of the protein to undergo clotting. Conversely, oxidation of plasma protease inhibitors can lead to an increase of clotting activity. Our research is designed to elucidate the conditions under which proteins acquire oxidative modifications and to ensure that the assays employed provide a correct assessment of the types of modifications incurred. In recently completed experiments, we determined that the carbohydrate moieties of glycoproteins do not undergo oxidative modification to carbonyl groups under conditions that oxidize amino acid side chains. In addition, we validated the use of a Western blot assay for protein carbonyls for use on glycoproteins. Currents studies are aimed at determining the extent to which proteins undergo oxidative modification within cells exposed to varying growth conditions, including oxidative stress. Because cellular lipids are also targets for oxidative attack and can modify proteins through conjugation reactions, it will be important to distinguish between lipid-derived protein modifications and direct protein oxidative modification. Assays to accomplish this are currently being developed.