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

doi:10.1074/mcp.RA118.000907

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 journal › Article › peer-review

14 Citations (Scopus)

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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 language	English
Pages (from-to)	182-199
Number of pages	18
Journal	Molecular & cellular proteomics : MCP
Volume	18
Issue number	2
DOIs	https://doi.org/10.1074/mcp.RA118.000907
Publication status	Published - Feb 2019
Externally published	Yes

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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10.1074/mcp.RA118.000907

Publisher version (open access)Final published version, 4.28 MBLicence: CC BY

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Kawahara, R., Rosa-Fernandes, L., Dos Santos, A. F., Bandeira, C. L., Dombrowski, J. G., Souza, R. M., Da Fonseca, M. P., Festuccia, W. T., Labriola, L., Larsen, M. R., Marinho, C. R. F., & Palmisano, G. (2019). Integrated proteomics reveals apoptosis-related mechanisms associated with placental malaria. Molecular & cellular proteomics : MCP, 18(2), 182-199. https://doi.org/10.1074/mcp.RA118.000907

@article{75fc405722da4b07baaa8c1d9de9aaa1,

title = "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.",

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",

author = "Rebeca Kawahara and Livia Rosa-Fernandes and {Dos Santos}, {Anc{\'e}ly Ferreira} and Bandeira, {Carla Let{\'i}cia} and Dombrowski, {Jamille G.} and Souza, {Rodrigo M.} and {Da Fonseca}, {Micaella Pereira} and Festuccia, {William T.} and Leticia Labriola and Larsen, {Martin R.} and Marinho, {Claudio R. F.} and Giuseppe Palmisano",

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.",

year = "2019",

month = feb,

doi = "10.1074/mcp.RA118.000907",

language = "English",

volume = "18",

pages = "182--199",

journal = "Molecular & cellular proteomics : MCP",

issn = "1535-9476",

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Kawahara, R, Rosa-Fernandes, L, Dos Santos, AF, Bandeira, CL, Dombrowski, JG, Souza, RM, Da Fonseca, MP, Festuccia, WT, Labriola, L, Larsen, MR, Marinho, CRF & Palmisano, G 2019, 'Integrated proteomics reveals apoptosis-related mechanisms associated with placental malaria', Molecular & cellular proteomics : MCP, vol. 18, no. 2, pp. 182-199. https://doi.org/10.1074/mcp.RA118.000907

TY - JOUR

T1 - Integrated proteomics reveals apoptosis-related mechanisms associated with placental malaria

AU - Kawahara, Rebeca

AU - Rosa-Fernandes, Livia

AU - Dos Santos, Ancély Ferreira

AU - Bandeira, Carla Letícia

AU - Dombrowski, Jamille G.

AU - Souza, Rodrigo M.

AU - Da Fonseca, Micaella Pereira

AU - Festuccia, William T.

AU - Labriola, Leticia

AU - Larsen, Martin R.

AU - Marinho, Claudio R. F.

AU - Palmisano, Giuseppe

N1 - 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.

PY - 2019/2

Y1 - 2019/2

N2 - 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.

AB - 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.

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KW - Disease Models, Animal

KW - Female

KW - Glycosylation

KW - Humans

KW - MAP Kinase Signaling System

KW - Malaria, Falciparum/drug therapy

KW - Mice

KW - Phosphorylation

KW - Placenta/metabolism

KW - Pregnancy

KW - Pregnancy Complications, Parasitic/drug therapy

KW - Protein Interaction Maps

KW - Proteomics/methods

UR - http://www.scopus.com/inward/record.url?scp=85060946245&partnerID=8YFLogxK

U2 - 10.1074/mcp.RA118.000907

DO - 10.1074/mcp.RA118.000907

M3 - Article

C2 - 30242111

SN - 1535-9476

VL - 18

SP - 182

EP - 199

JO - Molecular & cellular proteomics : MCP

JF - Molecular & cellular proteomics : MCP

IS - 2

ER -

Integrated proteomics reveals apoptosis-related mechanisms associated with placental malaria

Abstract

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Keywords

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