Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro

dc.contributor.authorStiebler, Renataen_ZA
dc.contributor.authorHoang, Anh Nen_ZA
dc.contributor.authorEgan, Timothy Jen_ZA
dc.contributor.authorWright, David Wen_ZA
dc.contributor.authorOliveira, Marcus Fen_ZA
dc.date.accessioned2015-11-18T07:13:20Z
dc.date.available2015-11-18T07:13:20Z
dc.date.issued2010en_ZA
dc.description.abstractBACKGROUND: Hemozoin (Hz) is a heme crystal that represents a vital pathway for heme disposal in several blood-feeding organisms. Recent evidence demonstrated that β-hematin (βH) (the synthetic counterpart of Hz) formation occurs under physiological conditions near synthetic or biological hydrophilic-hydrophobic interfaces. This seems to require a heme dimer acting as a precursor of Hz crystals that would be formed spontaneously in the absence of the competing water molecules bound to the heme iron. Here, we aimed to investigate the role of medium polarity on spontaneous βH formation in vitro . METHODOLOGY/PRINCIPAL FINDINGS: We assessed the effect of water content on spontaneous βH formation by using the aprotic solvent dimethylsulfoxide (DMSO) and a series of polyethyleneglycols (PEGs). We observed that both DMSO and PEGs (3.350, 6.000, 8.000, and 22.000) increased the levels of soluble heme under acidic conditions. These compounds were able to stimulate the production of βH crystals in the absence of any biological sample. Interestingly, the effects of DMSO and PEGs on βH formation were positively correlated with their capacity to promote previous heme solubilization in acidic conditions. Curiously, a short chain polyethyleneglycol (PEG 300) caused a significant reduction in both soluble heme levels and βH formation. Finally, both heme solubilization and βH formation strongly correlated with reduced medium water activity provided by increased DMSO concentrations. CONCLUSIONS: The data presented here support the notion that reduction of the water activity is an important mechanism to support spontaneous heme crystallization, which depends on the previous increase of soluble heme levels.en_ZA
dc.identifier.apacitationStiebler, R., Hoang, A. N., Egan, T. J., Wright, D. W., & Oliveira, M. F. (2010). Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro. <i>PLoS One</i>, http://hdl.handle.net/11427/15155en_ZA
dc.identifier.chicagocitationStiebler, Renata, Anh N Hoang, Timothy J Egan, David W Wright, and Marcus F Oliveira "Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro." <i>PLoS One</i> (2010) http://hdl.handle.net/11427/15155en_ZA
dc.identifier.citationStiebler, R., Hoang, A. N., Egan, T. J., Wright, D. W., & Oliveira, M. F. (2009). Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro. PloS one, 5(9), e12694-e12694. doi:10.1371/journal.pone.0012694en_ZA
dc.identifier.ris TY - Journal Article AU - Stiebler, Renata AU - Hoang, Anh N AU - Egan, Timothy J AU - Wright, David W AU - Oliveira, Marcus F AB - BACKGROUND: Hemozoin (Hz) is a heme crystal that represents a vital pathway for heme disposal in several blood-feeding organisms. Recent evidence demonstrated that β-hematin (βH) (the synthetic counterpart of Hz) formation occurs under physiological conditions near synthetic or biological hydrophilic-hydrophobic interfaces. This seems to require a heme dimer acting as a precursor of Hz crystals that would be formed spontaneously in the absence of the competing water molecules bound to the heme iron. Here, we aimed to investigate the role of medium polarity on spontaneous βH formation in vitro . METHODOLOGY/PRINCIPAL FINDINGS: We assessed the effect of water content on spontaneous βH formation by using the aprotic solvent dimethylsulfoxide (DMSO) and a series of polyethyleneglycols (PEGs). We observed that both DMSO and PEGs (3.350, 6.000, 8.000, and 22.000) increased the levels of soluble heme under acidic conditions. These compounds were able to stimulate the production of βH crystals in the absence of any biological sample. Interestingly, the effects of DMSO and PEGs on βH formation were positively correlated with their capacity to promote previous heme solubilization in acidic conditions. Curiously, a short chain polyethyleneglycol (PEG 300) caused a significant reduction in both soluble heme levels and βH formation. Finally, both heme solubilization and βH formation strongly correlated with reduced medium water activity provided by increased DMSO concentrations. CONCLUSIONS: The data presented here support the notion that reduction of the water activity is an important mechanism to support spontaneous heme crystallization, which depends on the previous increase of soluble heme levels. DA - 2010 DB - OpenUCT DO - 10.1371/journal.pone.0012694 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro TI - Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro UR - http://hdl.handle.net/11427/15155 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15155
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0012694
dc.identifier.vancouvercitationStiebler R, Hoang AN, Egan TJ, Wright DW, Oliveira MF. Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro. PLoS One. 2010; http://hdl.handle.net/11427/15155.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2010 Stiebler et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherHemeen_ZA
dc.subject.otherCrystallizationen_ZA
dc.subject.otherCrystalsen_ZA
dc.subject.otherNucleationen_ZA
dc.subject.otherScanning electron microscopyen_ZA
dc.subject.otherPigmentsen_ZA
dc.subject.otherSolubilityen_ZA
dc.subject.otherCrystal structureen_ZA
dc.titleIncrease on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitroen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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