Ricerc@Sapienza

Among the reactive species with oxidant action produced in organisms, hypochlorite (HOCl) is released in the extracellular environment as a key component of the inflammatory immune response in mammals. It has bactericidal activity but collateral damage to host tissues is also highly likely, and proteins are by far the major targets of HOCl-mediated modifications since are rich of potential reactive sites. Regarding the possible consequences of HOCl-induced chemical modification on protein behavior, at least two classes of proteins could be defined: those that do not aggregate and can even become effective chaperones, and those that become prone to precipitation.
We recently investigated the fate of Human Serum Albumin (HSA), the most abundant protein in blood plasma, undergoing HOCl-induced chemical damage at increasing doses of the oxidant, by applying a combination of techniques aimed at obtaining both chemical and structural information directly in solution. This led to discover a reproducible structural transition of the protein induced above a critical level of oxidative modification which could be relevant to explain the general suitability of the albumin structure to work as a scavenger in blood.
In the project we would like to characterize the consequences of HOCl-induced damage on another highly studied protein, Hen Egg White Lysozyme (HEWL). Preliminary experiments suggested that HEWL, differently from HSA, undergoes aggregation and precipitation when oxidized with HOCl.
Understanding the molecular basis of protein resistance to chemical damage, or, on the other hand, of the processes leading to the formation of insoluble precipitates as a consequence of these oxidative modifications, can be relevant for understanding physiological phenomena taking place in conditions of chronical inflammation and oxidative stress. In addition this knowledge can be useful to prevent inactivation of enzymes or protein carriers in applications.