Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
Department of Industrial Chemistry, Faculty of Science, Aligarh Muslim University, Aligarh, India.
Curr Pharm Biotechnol. 2019;20(12):1028-1036. doi: 10.2174/1389201020666190731122806.
BACKGROUND & OBJECTIVE: The present study was aimed at characterizing the conformational alterations induced in human transferrin, the iron regulatory protein by glyoxal. Since protein aggregation is at the core of many disorders, thus interest in this domain has increased significantly during the past years.
In our present study, the effect of glyoxal was monitored on human transferrin using multispectroscopic and multi-microscopic studies.
Intrinsic fluorescence spectroscopy suggested changes in native conformation of human transferrin evident by decreased fluorescence and blue shift in the presence of glyoxal. Further, extrinsic fluorescence was retorted and the results showed the formation of aggregates; apparent by increased Congo red (CR) absorbance, Thioflavin T (ThT) and ANS fluorescence and TEM of human transferrin in the presence of glyoxal. Molecular docking was also employed to see which residues are at core of human transferrin and glyoxal interaction. Reactive oxygen species (ROS) generation assays revealed enhanced ROS levels by human transferrin after treatment with glyoxal.
Thus, our study proposes that glyoxal induces the formation of aggregates in human transferrin. These aggregates further generate ROS which are key players in the complications associated with diabetes mellitus, giving our study clinical perspective.
本研究旨在研究乙二醛诱导人转铁蛋白（一种铁调节蛋白）构象改变的特征。由于蛋白质聚集是许多疾病的核心，因此近年来人们对这一领域的兴趣显著增加。
在本研究中，我们使用多光谱和多显微镜研究监测了乙二醛对人转铁蛋白的影响。
荧光光谱表明，在乙二醛存在的情况下，人转铁蛋白的天然构象发生了变化，表现为荧光强度降低和蓝移。此外，还进行了荧光外推实验，结果表明在乙二醛存在的情况下形成了聚集体；刚果红（CR）吸收增加、硫黄素 T（ThT）和 ANS 荧光增强以及人转铁蛋白的 TEM 图像表明了这一点。还进行了分子对接，以观察哪些残基是人转铁蛋白和乙二醛相互作用的核心。活性氧（ROS）生成测定显示，乙二醛处理后人转铁蛋白的 ROS 水平升高。
因此，我们的研究表明，乙二醛诱导人转铁蛋白形成聚集体。这些聚集体进一步产生 ROS，ROS 是与糖尿病相关并发症的关键因素，使我们的研究具有临床意义。
