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Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins
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Document Title
Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins
Author
Ponmee N, Chuchue T, Wilairat P, Yuthavong Y, Kamchonwongpaisan S
Name from Authors Collection
Affiliations
National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Mahidol University
Type
Article
Source Title
BIOCHEMICAL PHARMACOLOGY
ISSN
0006-2952
Year
2007
Volume
74
Issue
1
Open Access
Green Accepted
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI
10.1016/j.bcp.2007.03.008
Format
Abstract
Artemisinin loses its antimalarial activity on prolonged exposure to erythrocytes, especially alpha-thalassemic erythrocytes. In this report, we show that the major artemisinin-inactivating factor in cytosol of normal erythrocytes was heat-labile but a heat-stable factor from gamma-thalassemic cells also played a significant role in reducing artemisinin effectiveness, which was shown to be heme released from hemoglobin (Hb). Studies of fractionated lysate from genetically normal erythrocytes revealed that the protein fraction with molecular weight greater than 100 kDa was capable of reducing artemisinin effectiveness more readily than lower molecular weight fraction. Catalase and Hb A, but not selenoprotein glutathione peroxidase, were capable of reducing artemisinin effectiveness. Hemin (ferriprotoporphyrin IX) also reduced artemisinin effectiveness in a concentration- and time-dependent manner. It is concluded that heme and heme-containing proteins in erythrocyte are largely responsible for reducing artemisinin effectiveness and may contribute to resistance of Plasmodium falciparum infecting alpha-thalassemic erythrocytes observed in vitro. (c) 2007 Elsevier Inc. All rights reserved.
Keyword
Artemisinin | Catalase | Heme | Malaria | Plasmodium falciparum | Thalassemia
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
NIAID NIH HHS [U01 AI035827-06, U01-AI35827] Funding Source: Medline; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI035827] Funding Source: NIH RePORTER
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