Inhibition of Protein Fibrillation by Hydrogen Sulfide¹

Abstract

Amyloid fibrils are misfolded proteins, which are often associated with various neurodegenerative diseases such as Alzheimer's. The amount of hydrogen sulfide (H 2 S) is known to be reduced in the brain tissue of people diagnosed with Alzheimer's disease relative to that of healthy individuals. Hen Egg-White Lysozyme (HEWL) forms typical β-sheet-rich fibrils during 70 minutes at low pH and high temperatures. These results are consistent with the ThT findings that β-sheets structure is also present in myoglobin (Mb), and hemoglobin (Hb) in the presence of 45% TFE. The addition of H 2 S in the process completely inhibits the formation of amyloid fibrils in HEWL, Mb, and Hb as revealed by several spectroscopic techniques. Non-resonance Raman bands corresponding to disulfide (RSSR) vibrational modes in the 550-500 cm-1 spectral range decreases in intensity and is accompanied by the appearance of a new 490 cm-1 band assigned to the trisulfide group (RSSSR). Intrinsic tryptophan fluorescence shows a partial denaturation of HEWL containing trisulfide bonds. Overall, the Mb and Hb result ties excellent with the HEWL data showing that the presence of H 2 S during these proteins fibrillation processes protects the α-helical protein structures, preventing the formation of amyloids in these different proteins moieties.

Inhibition of amyloid formation of bovine hemoglobin by bioactive phenolic acids: an elaborate investigation into their binding properties with the protein using multi-spectroscopic and computational techniques

“…Health disorders associated with hemoglobin fibrillation include diabetes mellitus, hemophilia, hemolytic anemia, cardiovascular diseases, and renal diseases. 120–123 In this study, fibrillation of BHb was carried out with fructose, as literature studies report that the fructation of hemoglobin leads to numerous structural changes and modifications of protein function. These include heme loss resulting in iron release and ROS generation, a transition of α to β conformation, increase in protein surface hydrophobicity, loss of oxygen binding affinity, reduced peroxidase activity, and an increase in esterase activity.…”

In vitro interactions of esculin and esculetin with bovine hemoglobin alter its structure and inhibit aggregation: insights from spectroscopic and computational studies

“…Any imbalance in physiological levels of hemoglobin, which could be due to protein loss of function, is closely linked to various diseases such as hemophilia, hemolytic anemia, diabetes mellitus, cardiovascular diseases, and renal diseases. [77][78][79][80] The fructation of hemoglobin has been reported to cause a number of structural alterations and functional modifications of the protein, which include heme loss which results in the release of iron and free radical production, 81 ultimately leading to an a to b conformational transition, increasing hydrophobicity of the protein surface, interfering with oxygen affinity and peroxidase activity and conversely enhancing esterase activity. 82,83 In this study, BHb was fibrillated in the presence of fructose and the anti-fibrillating properties of esculin and esculetin were monitored using various methodologies.…”