Plasmodium vivax inhibits erythroid cell growth through altered phosphorylation of the cytoskeletal protein ezrin

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dc.contributor.authorTasanee Panichakul
dc.contributor.authorSaranyoo Ponnikorn
dc.contributor.authorSittiruk Roytrakul
dc.contributor.authorAtchara Paemanee
dc.contributor.authorSuthathip Kittisenachai
dc.contributor.authorSuradej Hongeng
dc.contributor.authorRachanee Udomsangpetch
dc.date.accessioned2025-03-10T07:36:30Z
dc.date.available2025-03-10T07:36:30Z
dc.date.issued2015
dc.description.abstractBackground: The underlying causes of severe malarial anaemia are multifactorial. In previously reports, Plasmodium vivax was found to be able to directly inhibited erythroid cell proliferation and differentiation. The molecular mechanisms underlying the suppression of erythropoiesis by P. vivax are remarkably complex and remain unclear. In this study, a phosphoproteomic approach was performed to dissect the molecular mechanism of phosphoprotein regulation, which is involved in the inhibitory effect of parasites on erythroid cell development. Methods: This study describes the first comparative phosphoproteome analysis of growing erythroid cells (gECs), derived from human haematopoietic stem cells, exposed to lysates of infected erythrocytes (IE)/uninfected erythrocytes (UE) for 24, 48 and 72 h. This study utilized IMAC phosphoprotein isolation directly coupled with LC MS/MS analysis. Results: Lysed IE significantly inhibited gEC growth at 48 and 72 h and cell division resulting in the accumulation of cells in G0 phase. The relative levels of forty four phosphoproteins were determined from gECs exposed to IE/UE for 24-72 h and compared with the media control using the label-free quantitation technique. Interestingly, the levels of three phosphoproteins: ezrin, alpha actinin-1, and Rho kinase were significantly (p_<_0.05) altered. These proteins display interactions and are involved in the regulation of the cellular cytoskeleton. Particularly affected was ezrin (phosphorylated at Thr567), which is normally localized to gEC cell extension peripheral processes. Following exposure to IE, for 48-72 h, the ezrin signal intensity was weak or absent. This result suggests that phospho-ezrin is important for actin cytoskeleton regulation during erythroid cell growth and division. Conclusions: These findings suggest that parasite proteins are able to inhibit erythroid cell growth by down-regulation of ezrin phosphorylation, leading to ineffective erythropoiesis ultimately resulting in severe malarial anaemia. A better understanding of the mechanisms of ineffective erythropoiesis may be beneficial in the development of therapeutic strategies to prevent severe malarial anaemia. � 2015 Panichakul et al.; licensee BioMed Central.
dc.identifier.citationMalaria Journal
dc.identifier.doi10.1186/s12936-015-0648-9
dc.identifier.issn14752875
dc.identifier.scopus2-s2.0-84927521998
dc.identifier.urihttps://repository.dusit.ac.th//handle/123456789/4838
dc.languageEnglish
dc.publisherBioMed Central Ltd.
dc.rightsAll Open Access; Gold Open Access; Green Open Access
dc.rights.holderScopus
dc.subjectAnaemia
dc.subjectErythroid cells
dc.subjectEzrin
dc.subjectHaematopoiesis stem cells
dc.subjectIneffective erythropoiesis
dc.subjectPhosphoproteins
dc.subjectPlasmodium vivax
dc.titlePlasmodium vivax inhibits erythroid cell growth through altered phosphorylation of the cytoskeletal protein ezrin
dc.typeArticle
mods.location.urlhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84927521998&doi=10.1186%2fs12936-015-0648-9&partnerID=40&md5=f74eb5934eaa45d5eed36b549c905e03
oaire.citation.issue1
oaire.citation.volume14
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