Document Detail


Molecular genetics evidence for the in vivo roles of the two major NADPH-dependent disulfide reductases in the malaria parasite.
MedLine Citation:
PMID:  20852334     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Malaria-associated pathology is caused by the continuous expansion of Plasmodium parasites inside host erythrocytes. To maintain a reducing intracellular milieu in an oxygen-rich environment, malaria parasites have evolved a complex antioxidative network based on two central electron donors, glutathione and thioredoxin. Here, we dissected the in vivo roles of both redox pathways by gene targeting of the respective NADPH-dependent disulfide reductases. We show that Plasmodium berghei glutathione reductase and thioredoxin reductase are dispensable for proliferation of the pathogenic blood stages. Intriguingly, glutathione reductase is vital for extracellular parasite development inside the insect vector, whereas thioredoxin reductase is dispensable during the entire parasite life cycle. Our findings suggest that glutathione reductase is the central player of the parasite redox network, whereas thioredoxin reductase fulfils a specialized and dispensable role for P. berghei. These results also indicate redundant roles of the Plasmodium redox pathways during the pathogenic blood phase and query their suitability as promising drug targets for antimalarial intervention strategies.
Authors:
Kathrin Buchholz; Elyzana D Putrianti; Stefan Rahlfs; R Heiner Schirmer; Katja Becker; Kai Matuschewski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-19
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2010-12-30     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37388-95     Citation Subset:  IM    
Affiliation:
Interdisciplinary Research Centre, Justus-Liebig University, Giessen 35390, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation
Gene Silencing*
Glutathione Reductase / chemistry,  genetics,  metabolism*
Humans
Malaria / parasitology
Mice
Mice, Inbred C57BL
NADP / metabolism*
Plasmodium berghei / chemistry,  cytology,  enzymology*,  genetics*,  growth & development
Protozoan Proteins / chemistry,  genetics,  metabolism*
Rats
Rats, Sprague-Dawley
Thioredoxin-Disulfide Reductase / chemistry,  genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Protozoan Proteins; 53-59-8/NADP; EC 1.8.1.7/Glutathione Reductase; EC 1.8.1.9/Thioredoxin-Disulfide Reductase
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