scholarly journals Serum Lipoproteins Promote Efficient Presentation of the Malaria Virulence Protein PfEMP1 at the Erythrocyte Surface

2007 ◽  
Vol 6 (9) ◽  
pp. 1584-1594 ◽  
Author(s):  
Sarah Frankland ◽  
Salenna R. Elliott ◽  
Francisca Yosaatmadja ◽  
James G. Beeson ◽  
Stephen J. Rogerson ◽  
...  

ABSTRACT The virulence of the malaria parasite Plasmodium falciparum is related to its ability to express a family of adhesive proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1) at the infected red blood cell surface. The mechanism for the transport and delivery of these adhesins to the erythrocyte membrane is only poorly understood. In this work, we have used specific immune reagents in a flow cytometric assay to monitor the effects of serum components on the surface presentation of PfEMP1. We show that efficient presentation of the A4 and VAR2CSA variants of PfEMP1 is dependent on the presence of serum in the bathing medium during parasite maturation. Lipid-loaded albumin supports parasite growth but allows much less efficient presentation of PfEMP1 at the red blood cell surface. Analysis of the serum components reveals that lipoproteins, especially those of the low-density lipoprotein fraction, promote PfEMP1 presentation. Cytoadhesion of infected erythrocytes to the host cell receptors CD36 and ICAM-1 is also decreased in infected erythrocytes cultured in the absence of serum. The defect appears to be in the transfer of PfEMP1 from parasite-derived structures known as the Maurer's clefts to the erythrocyte membrane or in surface conformation rather than a down-regulation or switching of particular PfEMP1 variants.

2021 ◽  
Author(s):  
Olivia M. S. Carmo ◽  
Gerald J Shami ◽  
Dezerae Cox ◽  
Boyin Liu ◽  
Adam J Blanch ◽  
...  

Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on the surface of infected red blood cells, underpins P. falciparum malaria pathogenicity. Here we describe a protein PF3D7_0301700 (PTP7), that functions at the nexus between the intermediate trafficking organelle, the Maurer’s cleft, and the red blood cell surface. Genetic disruption of PTP7 leads to accumulation of vesicles at the Maurer’s clefts, grossly aberrant knob morphology, and failure to deliver EMP1 to the red blood cell surface.  We show that an expanded low complexity sequence in the C-terminal region of PTP7, found only in the Laverania clade of Plasmodium , is critical for efficient virulence protein trafficking.


2000 ◽  
Vol 11 (8) ◽  
pp. 2643-2655 ◽  
Author(s):  
Lolita Zaliauskiene ◽  
Sunghyun Kang ◽  
Christie G. Brouillette ◽  
Jacob Lebowitz ◽  
Ramin B. Arani ◽  
...  

How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this study, we demonstrate that the “signal” within the TM necessary and sufficient for down-regulation is Thr11Gln17Thr19 (numbering in TM). Transplantation of these polar residues into the wild-type TR promotes receptor down-regulation that can be demonstrated by changes in protein half-life and in receptor recycling. Surprisingly, this modification dramatically increases the TR internalization rate as well (∼79% increase). Sucrose gradient centrifugation and cross-linking studies reveal that propensity of the receptors to self-associate correlates with down-regulation. Interestingly, a number of cell surface proteins that contain TM polar residues are known to be efficiently down-regulated, whereas recycling receptors for low-density lipoprotein and transferrin conspicuously lack these residues. Our data, therefore, suggest a simple model in which specific residues within the TM sequences dramatically influence the fate of membrane proteins after endocytosis, providing an alternative signal for down-regulation of receptor complexes to the well-characterized cytoplasmic tail targeting signals.


2015 ◽  
Vol 39 (2) ◽  
pp. 26-31
Author(s):  
Alia Hussein Ali

     The aim of this study is to explain the effect of Ethanolic extract 70% of Metracaria chamomella on some physiological parameters in male rabbits. Twelve adult male rabbits were used in this study and were divided equally into two groups: First group was control (C) and received normal saline for four weeks, the second group (Treated group) was intubated orally with ethanolic extract of Metracaria chamomella in a dose 70 mg/kg B.W. for four weeks. Blood samples were collected by heart puncture from each animal at the end of experiment. Blood sample was divided into a part for hematological study and a part for biochemical analysis. The value of serum urea, and creatinine were reduced in animals that received Metracaria chamomella extract at dose of 70 mg/ kg B.W. as compared with the control group. Significant decrease in serum activity of aspartate aminotransferase alanine aminotransferase and alkaline phosphatase activity was observed in Metracaria treated animal as compared with the control group. This study explained that there was significant increase in serum total protein, serum albumin and serum globulin in treated animals as compared with the control group. The value of total cholesterol, serum triacylglycerol, serum low density lipoprotein cholesterol and very low density lipoprotein cholesterol concentration were reduced significantly in animal received Metracaria chamomella extract while the high density lipoprotein cholesterol was elevated significantly as compared with control group. While the effect of Metracaria chamomella extract on blood picture showed no changes in red blood cell count, hemoglobin concentration and hematocrit value but showed significant decrease in platelet count, and significant   increase in white blood cell count as compared with control group. Over all this study explained that Metracaria chamomella extract had Reno protective and hypolipidimic effect in male rabbit.  


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Maria del Pilar Quintana ◽  
Jun-Hong Ch’ng ◽  
Kirsten Moll ◽  
Arash Zandian ◽  
Peter Nilsson ◽  
...  

2018 ◽  
Vol 6 ◽  
pp. 205031211875666 ◽  
Author(s):  
Alemu Gebrie ◽  
Natesan Gnanasekaran ◽  
Menakath Menon ◽  
Mekonnen Sisay ◽  
Abriham Zegeye

Introduction: Hypertension and dyslipidemia are the two coexisting and synergizing major risk factors for cardiovascular diseases. The cellular constituents of blood affect the volume and viscosity of blood, thus playing a key role in regulating blood pressure. Overweight and obesity are key determinants of adverse metabolic changes including an increase in blood pressure. The aim of this study was to evaluate lipid profiles and hematological parameters in hypertensive patients at Debre Markos Referral Hospital, Northwest Ethiopia. Methods: Laboratory-based cross-sectional study was conducted in 100 eligible hypertensive patients at the hospital. The required amount of blood was withdrawn from the patients by healthcare professionals for immediate automated laboratory analyses. Data were collected on socio-demographic factors, anthropometric measurements, blood pressure, lipid profiles, and hematological parameters. Result: The mean serum levels of triglyceride, total cholesterol, and low-density lipoprotein were significantly higher than their respective cut-off values in the hypertensive patients. Besides, 54%, 52%, 35%, and 11% of the hypertensive patients had abnormal low-density lipoprotein, total cholesterol, triglyceride, and high-density lipoprotein levels, respectively. Higher levels of low-density lipoprotein, hemoglobin, and red blood cell count were observed in the hypertensive patients whose blood pressure had been poorly controlled than the controlled ones ( p < 0.05). Waist circumference had a significant positive association with the serum levels of total cholesterol and white blood cell count ( p < 0.05). Conclusion: Hypertensive patients had a high prevalence of lipid profile abnormalities and poorly controlled blood pressure which synergize in accelerating other cardiovascular diseases. Some hematological parameters such as red blood cell count are also increased as do the severity of hypertension.


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