2016
DOI: 10.1038/srep22093
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Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2α) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum

Abstract: In mammals, haem degradation to biliverdin (BV) through the action of haem oxygenase (HO) is a critical step in haem metabolism. The malaria parasite converts haem into the chemically inert haemozoin to avoid toxicity. We discovered that the knock-out of HO in P. berghei is lethal; therefore, we investigated the function of biliverdin (BV) and haem in the parasite. Addition of external BV and haem to P. falciparum-infected red blood cell (RBC) cultures delays the progression of parasite development. The search… Show more

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Cited by 14 publications
(11 citation statements)
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“…Hb is present at low millimolar concentrations in the RBC cytoplasm and is imported into the DV via cytostomes or endocytic vesicles 42 , 43 . In the DV, Hb catabolism employs aspartic and cysteine proteases that generate oligopeptides 44 as well as free Fe 2+ -heme (which is biomineralized into chemically inert hemozoin 8 , 45 47 ). Oligopeptides are degraded by the Cl − dependent exopeptidase dipeptidyl aminopeptidase 1 (PfDPAP1) and the Zn 2+ and/or Mn 2+ -dependent peptidases falcilysin, aminopeptidase P (PfAPP), and aminopeptidase N (PfA-M1).…”
Section: Introductionmentioning
confidence: 99%
“…Hb is present at low millimolar concentrations in the RBC cytoplasm and is imported into the DV via cytostomes or endocytic vesicles 42 , 43 . In the DV, Hb catabolism employs aspartic and cysteine proteases that generate oligopeptides 44 as well as free Fe 2+ -heme (which is biomineralized into chemically inert hemozoin 8 , 45 47 ). Oligopeptides are degraded by the Cl − dependent exopeptidase dipeptidyl aminopeptidase 1 (PfDPAP1) and the Zn 2+ and/or Mn 2+ -dependent peptidases falcilysin, aminopeptidase P (PfAPP), and aminopeptidase N (PfA-M1).…”
Section: Introductionmentioning
confidence: 99%
“…Surface expressed enolase has been identified as a plasminogen receptor, which can be subsequently converted into active plasmin, a strong serine protease facilitating the host invasion process ( Pancholi, 2001 ; Ghosh and Jacobs-Lorena, 2011 ; Diaz-Ramos et al, 2012 ). In recent years, a variety of pathogenic parasites have also been found to express enolase on their surface, and it is thus thought to aid with host invasion ( Figueiredo et al, 2015 ; Alves et al, 2016 ; Mahana et al, 2016 ). Remarkably, enolase has also been identified on the surface of vector-borne pathogens (e.g., Plasmodium falciparum and Borrelia burgdorferi ), and plays an important role during pathogen invasion of vector gut by binding mammalian plasminogen ( Ghosh et al, 2011 ; Toledo et al, 2012 ).…”
Section: Introductionmentioning
confidence: 99%
“…The host catalytically degrades hemin into biliverdin (BV) [197]. Nanomolar concentration of BV can delay the intraerythrocytic development of P. falciparum by targeting parasite enolase [198]. Moreover, the malaria digestive vacuole (DV), where hemoglobin degradation and hemozoin formation takes place, is also an important compartment for calcium homeostasis [199].…”
Section: Formulation Techniquesmentioning
confidence: 99%