Hydrogen Sulfide (H2S) Limits Amyloid Development in Hen Egg White Lysozyme (HEWL) as a Function of Concentration

Abstract

Amyloid fibrils are conformations of misfolded proteins with a stable beta‐sheet structure. These structures aggregate in various parts of the human body and disrupt the healthy functioning of vital organs, causing diseases known as amyloidosis. Lysozyme is a bacteriolytic enzyme that is synthesized in macrophages, gastrointestinal cells, and hepatocytes and it is commonly found in human saliva and tears; when this protein misfolds, its amyloidosis can have devastating effects on the health, causing sicca syndrome (dry eyes and mouth), rheumatoid arthritis and even renal failure. Here, it is shown that by adding hydrogen sulfide (H2S) to hen egg white lysozyme (HEWL) the formation of amyloid fibers is inhibited. This inhibition results in small spherical aggregates of unordered protein that exhibit almost no cytotoxicity. This effect was further investigated by exposing HEWL to various concentrations of H2S and exploring the protein's conformational changes. This was done through atomic force microscopy (AFM), non‐resonance Raman spectroscopy and circular dichroism (CD). The results show that when H2S was present, the protein did not undergo fibrillation and instead kept a secondary structure alike its native structure, with this effect increasing as a function of H2S concentration. Additionally, it is seen that HEWL does not form fibers and instead organizes itself in spherical aggregates and that these new aggregates have a higher abundance of trisulfide bonds (S‐S‐S). This fact provides valuable information about the mechanism through which H2S might inhibit the pathogenic fibrillation. Further studies are being conducted to unravel the exact mechanism through which hydrogen sulfide prevents the aggregation of lysozyme; However, the effects observed open the door to a possible preventive therapy for deadly amyloidosis disorders.Support or Funding InformationMARC‐U‐STAR Program, UPR‐MayaguezNIH Grant number: 2T34GM008419‐26RISE‐E‐BASE Program, UPR‐MayaguezNIH Grant number: 1R25GM127191‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.