Integrated Proteomics Reveals Apoptosis-related Mechanisms Associated with Placental Malaria.

ABSTRACT

Malaria in pregnancy is a public health concern in malaria-endemic areas. Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction. Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection). We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria. A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas. This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.