Integrated proteomics reveals apoptosis-related mechanisms associated with placental malaria

Rebeca Kawahara, Livia Rosa-Fernandes, Ancély Ferreira Dos Santos, Carla Letícia Bandeira, Jamille G. Dombrowski, Rodrigo M. Souza, Micaella Pereira Da Fonseca, William T. Festuccia, Leticia Labriola, Martin R. Larsen, Claudio R. F. Marinho*, Giuseppe Palmisano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
1 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)182-199
Number of pages18
JournalMolecular & cellular proteomics : MCP
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2019
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Animals
  • Disease Models, Animal
  • Female
  • Glycosylation
  • Humans
  • MAP Kinase Signaling System
  • Malaria, Falciparum/drug therapy
  • Mice
  • Phosphorylation
  • Placenta/metabolism
  • Pregnancy
  • Pregnancy Complications, Parasitic/drug therapy
  • Protein Interaction Maps
  • Proteomics/methods

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