Microenvironment could trigger human apolipoproteína A-I amyloid folding

RAMELLA, N.; SCHINELLA, GUILLERMO; PRIETO, E. D.; RIMOLDI. O. J.; TRICERRI, M. A.

Salta

Congreso; XXXIX Congreso Nacional de la Sociedad Argentina de Biofísica.; 2010

Sociedad Argentina de Biofisica

Amyloidosis is characterized by extra cellular deposits of anomalous fibrillar proteins. Human apolipoprotein A-I (apoA-I) does not normally misfold. However, wild type apoA-I has been immuno localized in senile plaques and associated to atherosclerosis lesions. The environmental consequences that chronic inflammatory events could exert on protein structure and folding are important to be considered, as they could induce not only dysfunction but also the pathological deposition as amyloid- like aggregates. Here we analyze the possible consequences of cellular pathological landscapes–acidic or pro inflammatory environments - on the structure and folding of apoA-I, and we discuss the possibility of a change in the role of the protein from anti-to-proatherogenic depending on the modifications that different cellular environment can produce on its structure. We find that both, -mild acidification and activated neutrophil incubation-  promote protein misfolding, aggregation, and increased binding to the cellular matrix, thus favoring its deposition surrounding atherosclerosis lesions. Thus, we conclude that apoA-I is not amyloidogenic, but it could induce in some extent non hereditary amyloidosis as a non-desired consequence.