PXD003772-1

PXD003772 is an original dataset announced via ProteomeXchange.

Title	Characterisation of the protein cargo of murine plasma microparticles released during experimental cerebral malaria
Description	Cerebral malaria (CM) is a severe complication of a Plasmodium falciparum infection and is still responsible for a high number of deaths and long term disabilities in children in sub-Saharan Africa. The pathogenesis of this syndrome remains incompletely understood but a number of mechanisms and effectors have been proposed, including plasma microparticles (MP). These submicron vesicles released by potentially all cells carry proteins and nucleic acids derived from the mother cell. In CM, their numbers are increased in patients’ circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their involvement in vascular damage. In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the overarching hypothesis that characterising this content could help in better understand CM pathogenesis. Using qualitative and quantitative high-throughput proteomics we compared MP proteins from non-infected mice and mice infected with P. berghei ANKA at two different stages of infection, i.e., pre-clinical phase and full blown syndrome. Overall, we identified 368 proteins, 60 of which were differentially expressed, as determined by quantitative comparison using the TMT® isobaric labelling. The analysis with Ingenuity® IPA highlighted important networks significantly represented among the proteins over-expressed (n=42) or identified only (n=21) in ECM, comprising mechanisms already proposed to be involved in CM, such as endothelial activation. Two proteins of interest, carbonic anhydrase I (CA-I) and S100A8, were verified by western blot on newly collected MP samples from DBA/1 (n=16) and C57BL/6 (n=8) mice, and confirmed to be associated with ECM MP. These results demonstrate that MP protein cargo represents a novel ECM pathogenic trait to consider in the understanding of CM pathogenesis. The identification of the cellular source of MP containing proteins associated to the disease state will contribute to further understanding their involvement in CM.
HostingRepository	PRIDE
AnnounceDate	2016-12-13
AnnouncementXML	Submission_2016-12-13_01:51:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalia Tiberti
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-11 03:10:15	ID requested
⏵ 1	2016-12-13 01:51:51	announced
2	2017-10-24 02:40:04	announced	Updated project metadata.

Tiberti N, Latham SL, Bush S, Cohen A, Opoka RO, John CC, Juillard A, Grau GE, Combes V, Exploring experimental cerebral malaria pathogenesis through the characterisation of host-derived plasma microparticle protein content. Sci Rep, 6():37871(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Microparticles, Protein cargo, Experimental cerebral malaria, Tandem Mass Tag (TMT), QExactive Orbitrap

Valery Combes
contact affiliation	School of Life Sciences Faculty of Sciences University of Technology Sydney Australia
contact email	valery.combes@uts.edu.au
lab head
Natalia Tiberti
contact affiliation	Translational Biomarker Group, Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland
contact email	natalia.tiberti@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003772
     1. Label: PRIDE project
     2. Name: Characterisation of the protein cargo of murine plasma microparticles released during experimental cerebral malaria