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Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Research

Comparative 1D Blue-Native electrophoresis analysis of Plasmodium falciparum and human proteins associated with cytoadherence

Authors: Yang Wu, Simon C. Wagstaff, Saeed A. Al-Harthi, Alister G. Craig

Published in: Malaria Journal | Issue 1/2018

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Abstract

Background

To understand more about changes to the molecular components that occur when host endothelium interacts with Plasmodium falciparum-infected erythrocytes, a combined technique of protein separation (1D Blue-Native electrophoresis) and mass spectrometry of infected erythrocytes with endothelial cells (EC) in a co-culture system has been used.

Methods

Native proteins were extracted from co-cultures and identified by mass spectrometry. Proteomic data from different parasite strains, either adhesion proficient (to endothelial cells) or non-adherent, were analysed in parallel to reveal protein associations linked to cytoadherence. Informatic approaches were developed to facilitate this comparison.

Results

Blue-Native gel separation and LC/MS/MS identification revealed major differences in samples produced from endothelial cell co-culture with adherent and non-adherent parasite strains. This approach enabled us to identify protein associations seen only with the adhesion proficient parasite strain.

Conclusions

The combination of proteomic and analytical approaches has identified differences between adherent and non-adherent parasite lines in co-culture with EC, providing potential candidates for complexes or associations formed during cytoadherence involved in cell structure, signalling and apoptosis.
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Literature
1.
go back to reference MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985;119:385–401.PubMedPubMedCentral MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985;119:385–401.PubMedPubMedCentral
2.
go back to reference Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10:143–5.CrossRefPubMed Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10:143–5.CrossRefPubMed
3.
go back to reference Singh H, Madnani K, Lim YB, Cao J, Preiser PR, Lim CT. Expression dynamics & physiologically relevant functional study of STEVOR in asexual stages of Plasmodium falciparum infection. Cell Microbiol. 2017;19:e12715.CrossRef Singh H, Madnani K, Lim YB, Cao J, Preiser PR, Lim CT. Expression dynamics & physiologically relevant functional study of STEVOR in asexual stages of Plasmodium falciparum infection. Cell Microbiol. 2017;19:e12715.CrossRef
4.
go back to reference Goel S, Palmkvist M, Moll K, Joannin N, Lara P, Akhouri RR, et al. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria. Nat Med. 2015;21:314–7.CrossRefPubMed Goel S, Palmkvist M, Moll K, Joannin N, Lara P, Akhouri RR, et al. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria. Nat Med. 2015;21:314–7.CrossRefPubMed
6.
go back to reference Gray C, McCormick C, Turner G, Craig A. ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Mol Biochem Parasitol. 2003;128:187–93.CrossRefPubMed Gray C, McCormick C, Turner G, Craig A. ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Mol Biochem Parasitol. 2003;128:187–93.CrossRefPubMed
7.
go back to reference McCormick CJ, Craig A, Roberts D, Newbold CI, Berendt AR. Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest. 1997;100:2521–9.CrossRefPubMedPubMedCentral McCormick CJ, Craig A, Roberts D, Newbold CI, Berendt AR. Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest. 1997;100:2521–9.CrossRefPubMedPubMedCentral
8.
go back to reference Yipp BG, Hickey MJ, Andonegui G, Murray AG, Looareesuwan S, Kubes P, et al. Differential roles of CD36, ICAM-1, and P-selectin in Plasmodium falciparum cytoadherence in vivo. Microcirculation. 2007;14:593–602.CrossRefPubMed Yipp BG, Hickey MJ, Andonegui G, Murray AG, Looareesuwan S, Kubes P, et al. Differential roles of CD36, ICAM-1, and P-selectin in Plasmodium falciparum cytoadherence in vivo. Microcirculation. 2007;14:593–602.CrossRefPubMed
9.
go back to reference Waller KL, Nunomura W, Cooke BM, Mohandas N, Coppel RL. Mapping the domains of the cytoadherence ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) that bind to the knob-associated histidine-rich protein (KAHRP). Mol Biochem Parasitol. 2002;119:125–9.CrossRefPubMed Waller KL, Nunomura W, Cooke BM, Mohandas N, Coppel RL. Mapping the domains of the cytoadherence ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) that bind to the knob-associated histidine-rich protein (KAHRP). Mol Biochem Parasitol. 2002;119:125–9.CrossRefPubMed
10.
go back to reference Ganguly AK, Ranjan P, Kumar A, Bhavesh NS. Dynamic association of PfEMP1 and KAHRP in knobs mediates cytoadherence during Plasmodium invasion. Sci Rep. 2015;5:8617.CrossRefPubMedPubMedCentral Ganguly AK, Ranjan P, Kumar A, Bhavesh NS. Dynamic association of PfEMP1 and KAHRP in knobs mediates cytoadherence during Plasmodium invasion. Sci Rep. 2015;5:8617.CrossRefPubMedPubMedCentral
11.
go back to reference Oberli A, Slater LM, Cutts E, Brand F, Mundwiler-Pachlatko E, Rusch S, et al. A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface. FASEB J. 2014;28:4420–33.CrossRefPubMedPubMedCentral Oberli A, Slater LM, Cutts E, Brand F, Mundwiler-Pachlatko E, Rusch S, et al. A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface. FASEB J. 2014;28:4420–33.CrossRefPubMedPubMedCentral
12.
go back to reference Oberli A, Zurbrugg L, Rusch S, Brand F, Butler ME, Day JL, et al. Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton. Cell Microbiol. 2016;18:1415–28.CrossRefPubMedPubMedCentral Oberli A, Zurbrugg L, Rusch S, Brand F, Butler ME, Day JL, et al. Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteins contribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein 1 to the host cell cytoskeleton. Cell Microbiol. 2016;18:1415–28.CrossRefPubMedPubMedCentral
13.
go back to reference Moss A. The angiopoietin: Tie 2 interaction: a potential target for future therapies in human vascular disease. Cytokine Growth Factor Rev. 2013;24:579–92.CrossRefPubMed Moss A. The angiopoietin: Tie 2 interaction: a potential target for future therapies in human vascular disease. Cytokine Growth Factor Rev. 2013;24:579–92.CrossRefPubMed
14.
go back to reference Schagger H, von Jagow G. Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal Biochem. 1991;199:223–31.CrossRefPubMed Schagger H, von Jagow G. Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal Biochem. 1991;199:223–31.CrossRefPubMed
15.
go back to reference Roberts DJ, Craig AG, Berendt AR, Pinches R, Nash G, Marsh K, et al. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992;57:689–92.CrossRef Roberts DJ, Craig AG, Berendt AR, Pinches R, Nash G, Marsh K, et al. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992;57:689–92.CrossRef
16.
go back to reference Ockenhouse CF, Ho M, Tandon NN, Van Seventer GA, Shaw S, White NJ, et al. Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. J Infect Dis. 1991;164:163–9.CrossRefPubMed Ockenhouse CF, Ho M, Tandon NN, Van Seventer GA, Shaw S, White NJ, et al. Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. J Infect Dis. 1991;164:163–9.CrossRefPubMed
17.
go back to reference Delemarre BJ, van der Kaay HJ. Tropical malaria contracted the natural way in the Netherlands. Ned Tijdschr Geneeskd. 1979;123:1981–2 (in Dutch).PubMed Delemarre BJ, van der Kaay HJ. Tropical malaria contracted the natural way in the Netherlands. Ned Tijdschr Geneeskd. 1979;123:1981–2 (in Dutch).PubMed
18.
go back to reference Trager W, Gill GS, Lawrence C, Nagel RL. Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood. Exp Parasitol. 1999;91:115–8.CrossRefPubMed Trager W, Gill GS, Lawrence C, Nagel RL. Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood. Exp Parasitol. 1999;91:115–8.CrossRefPubMed
19.
go back to reference Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91:3527–61.PubMed Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91:3527–61.PubMed
20.
go back to reference Jenkins N, Wu Y, Chakravorty S, Kai O, Marsh K, Craig A. Plasmodium falciparum intercellular adhesion molecule-1-based cytoadherence-related signaling in human endothelial cells. J Infect Dis. 2007;196:321–7.CrossRefPubMed Jenkins N, Wu Y, Chakravorty S, Kai O, Marsh K, Craig A. Plasmodium falciparum intercellular adhesion molecule-1-based cytoadherence-related signaling in human endothelial cells. J Infect Dis. 2007;196:321–7.CrossRefPubMed
21.
go back to reference Wu Y, Craig A. Comparative proteomic analysis of metabolically labelled proteins from Plasmodium falciparum isolates with different adhesion properties. Malar J. 2006;5:67.CrossRefPubMedPubMedCentral Wu Y, Craig A. Comparative proteomic analysis of metabolically labelled proteins from Plasmodium falciparum isolates with different adhesion properties. Malar J. 2006;5:67.CrossRefPubMedPubMedCentral
22.
go back to reference Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.CrossRefPubMed Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.CrossRefPubMed
23.
go back to reference Rappsilber J, Ishihama Y, Mann M. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal Chem. 2003;75:663–70.CrossRefPubMed Rappsilber J, Ishihama Y, Mann M. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal Chem. 2003;75:663–70.CrossRefPubMed
24.
go back to reference Washburn MP, Wolters D, Yates JR 3rd. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol. 2001;19:242–7.CrossRefPubMed Washburn MP, Wolters D, Yates JR 3rd. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol. 2001;19:242–7.CrossRefPubMed
25.
go back to reference Gisselberg JE, Zhang L, Elias JE, Yeh E. The prenylated proteome of Plasmodium falciparum reveals pathogen-specific prenylation activity and drug mechanism-of-action. Mol Cell Proteomics. 2017;16(Suppl 1):54–64.CrossRef Gisselberg JE, Zhang L, Elias JE, Yeh E. The prenylated proteome of Plasmodium falciparum reveals pathogen-specific prenylation activity and drug mechanism-of-action. Mol Cell Proteomics. 2017;16(Suppl 1):54–64.CrossRef
26.
go back to reference Miao J, Chen Z, Wang Z, Shrestha S, Li X, Li R, et al. Sex-specific biology of the human malaria parasite revealed from the proteomes of mature male and female gametocytes. Mol Cell Proteomics. 2017;16:537–51.CrossRefPubMedPubMedCentral Miao J, Chen Z, Wang Z, Shrestha S, Li X, Li R, et al. Sex-specific biology of the human malaria parasite revealed from the proteomes of mature male and female gametocytes. Mol Cell Proteomics. 2017;16:537–51.CrossRefPubMedPubMedCentral
27.
go back to reference Carpen O, Pallai P, Staunton DE, Springer TA. Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and alpha-actinin. J Cell Biol. 1992;118:1223–34.CrossRefPubMed Carpen O, Pallai P, Staunton DE, Springer TA. Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and alpha-actinin. J Cell Biol. 1992;118:1223–34.CrossRefPubMed
28.
go back to reference Pino P, Vouldoukis I, Kolb JP, Mahmoudi N, Desportes-Livage I, Bricaire F, et al. Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis. 2003;187:1283–90.CrossRefPubMed Pino P, Vouldoukis I, Kolb JP, Mahmoudi N, Desportes-Livage I, Bricaire F, et al. Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis. 2003;187:1283–90.CrossRefPubMed
29.
go back to reference Toure FS, Ouwe-Missi-Oukem-Boyer O, Bisvigou U, Moussa O, Rogier C, Pino P, et al. Apoptosis: a potential triggering mechanism of neurological manifestation in Plasmodium falciparum malaria. Parasite Immunol. 2008;30:47–51.PubMed Toure FS, Ouwe-Missi-Oukem-Boyer O, Bisvigou U, Moussa O, Rogier C, Pino P, et al. Apoptosis: a potential triggering mechanism of neurological manifestation in Plasmodium falciparum malaria. Parasite Immunol. 2008;30:47–51.PubMed
30.
go back to reference Zougbede S, Miller F, Ravassard P, Rebollo A, Ciceron L, Couraud PO, et al. Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood–brain barrier integrity. J Cereb Blood Flow Metab. 2011;31:514–26.CrossRefPubMed Zougbede S, Miller F, Ravassard P, Rebollo A, Ciceron L, Couraud PO, et al. Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood–brain barrier integrity. J Cereb Blood Flow Metab. 2011;31:514–26.CrossRefPubMed
31.
go back to reference Starr ME, Ueda J, Yamamoto S, Evers BM, Saito H. The effects of aging on pulmonary oxidative damage, protein nitration, and extracellular superoxide dismutase down-regulation during systemic inflammation. Free Radic Biol Med. 2011;50:371–80.CrossRefPubMed Starr ME, Ueda J, Yamamoto S, Evers BM, Saito H. The effects of aging on pulmonary oxidative damage, protein nitration, and extracellular superoxide dismutase down-regulation during systemic inflammation. Free Radic Biol Med. 2011;50:371–80.CrossRefPubMed
32.
go back to reference Li AY, Yang Q, Yang K. miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes. Mol Cell Biochem. 2015;400:173–81.CrossRefPubMed Li AY, Yang Q, Yang K. miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes. Mol Cell Biochem. 2015;400:173–81.CrossRefPubMed
33.
go back to reference Zafar S, Behrens C, Dihazi H, Schmitz M, Zerr I, Schulz-Schaeffer WJ, et al. Cellular prion protein mediates early apoptotic proteome alternation and phospho-modification in human neuroblastoma cells. Cell Death Dis. 2017;8:e2557.CrossRefPubMedPubMedCentral Zafar S, Behrens C, Dihazi H, Schmitz M, Zerr I, Schulz-Schaeffer WJ, et al. Cellular prion protein mediates early apoptotic proteome alternation and phospho-modification in human neuroblastoma cells. Cell Death Dis. 2017;8:e2557.CrossRefPubMedPubMedCentral
34.
go back to reference Hemmer CJ, Lehr HA, Westphal K, Unverricht M, Kratzius M, Reisinger EC. Plasmodium falciparum malaria: reduction of endothelial cell apoptosis in vitro. Infect Immun. 2005;73:1764–70.CrossRefPubMedPubMedCentral Hemmer CJ, Lehr HA, Westphal K, Unverricht M, Kratzius M, Reisinger EC. Plasmodium falciparum malaria: reduction of endothelial cell apoptosis in vitro. Infect Immun. 2005;73:1764–70.CrossRefPubMedPubMedCentral
35.
go back to reference Sullivan DC, Huminiecki L, Moore JW, Boyle JJ, Poulsom R, Creamer D, et al. EndoPDI, a novel protein-disulfide isomerase-like protein that is preferentially expressed in endothelial cells acts as a stress survival factor. J Biol Chem. 2003;278:47079–88.CrossRefPubMed Sullivan DC, Huminiecki L, Moore JW, Boyle JJ, Poulsom R, Creamer D, et al. EndoPDI, a novel protein-disulfide isomerase-like protein that is preferentially expressed in endothelial cells acts as a stress survival factor. J Biol Chem. 2003;278:47079–88.CrossRefPubMed
36.
go back to reference Romero IA, Amos CL, Greenwood J, Adamson P. Ezrin and moesin co-localise with ICAM-1 in brain endothelial cells but are not directly associated. Brain Res Mol Brain Res. 2002;105:47–59.CrossRefPubMed Romero IA, Amos CL, Greenwood J, Adamson P. Ezrin and moesin co-localise with ICAM-1 in brain endothelial cells but are not directly associated. Brain Res Mol Brain Res. 2002;105:47–59.CrossRefPubMed
37.
go back to reference Doerig C, Baker D, Billker O, Blackman MJ, Chitnis C, Dhar Kumar S, et al. Signalling in malaria parasites. The MALSIG consortium. Parasite. 2009;16:169–82.CrossRefPubMed Doerig C, Baker D, Billker O, Blackman MJ, Chitnis C, Dhar Kumar S, et al. Signalling in malaria parasites. The MALSIG consortium. Parasite. 2009;16:169–82.CrossRefPubMed
38.
go back to reference Wu Y, Cruz LN, Szestak T, Laing G, Molyneux GR, Garcia CR, et al. An external sensing system in Plasmodium falciparum-infected erythrocytes. Malar J. 2016;15:103.CrossRefPubMedPubMedCentral Wu Y, Cruz LN, Szestak T, Laing G, Molyneux GR, Garcia CR, et al. An external sensing system in Plasmodium falciparum-infected erythrocytes. Malar J. 2016;15:103.CrossRefPubMedPubMedCentral
39.
go back to reference Cruz LN, Wu Y, Ulrich H, Craig AG, Garcia CR. Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites. Biochim Biophys Acta. 2016;1860:1489–97.CrossRefPubMedPubMedCentral Cruz LN, Wu Y, Ulrich H, Craig AG, Garcia CR. Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites. Biochim Biophys Acta. 2016;1860:1489–97.CrossRefPubMedPubMedCentral
40.
41.
go back to reference Enomoto A, Ping J, Takahashi M. Girdin, a novel actin-binding protein, and its family of proteins possess versatile functions in the Akt and Wnt signaling pathways. Ann N Y Acad Sci. 2006;1086:169–84.CrossRefPubMed Enomoto A, Ping J, Takahashi M. Girdin, a novel actin-binding protein, and its family of proteins possess versatile functions in the Akt and Wnt signaling pathways. Ann N Y Acad Sci. 2006;1086:169–84.CrossRefPubMed
42.
go back to reference Gallego-Delgado J, Basu-Roy U, Ty M, Alique M, Fernandez-Arias C, Movila A, et al. Angiotensin receptors and beta-catenin regulate brain endothelial integrity in malaria. J Clin Invest. 2016;126:4016–29.CrossRefPubMedPubMedCentral Gallego-Delgado J, Basu-Roy U, Ty M, Alique M, Fernandez-Arias C, Movila A, et al. Angiotensin receptors and beta-catenin regulate brain endothelial integrity in malaria. J Clin Invest. 2016;126:4016–29.CrossRefPubMedPubMedCentral
Metadata
Title
Comparative 1D Blue-Native electrophoresis analysis of Plasmodium falciparum and human proteins associated with cytoadherence
Authors
Yang Wu
Simon C. Wagstaff
Saeed A. Al-Harthi
Alister G. Craig
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-018-2445-8

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