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.
Methods: In our present study, the effect of glyoxal was monitored on human transferrin using multispectroscopic
and multi-microscopic studies.
Results: 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.
Conclusion: 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.