Inhibition of Plasmodium falciparum proliferation in vitro by double-stranded RNA directed against malaria histone deacetylase
- Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120 (Thailand)
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand)
- Institute of Molecular Biology and Genetics, Mahidol University, Salaya, Nakornpathom 73170 (Thailand)
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand)
Acetylation and deacetylation of histones play important roles in transcription regulation, cell cycle progression and development events. The steady state status of histone acetylation is controlled by a dynamic equilibrium between competing histone acetylase and deacetylase (HDAC). We have used long PfHDAC-1 double-stranded (ds)RNA to interfere with its cognate mRNA expression and determined the effect on malaria parasite growth and development. Chloroquine- and pyrimethamine-resistant Plasmodium falciparum K1 strain was exposed to 1-25 {mu}g of dsRNA/ml of culture for 48 h and growth was determined by [{sup 3}H]-hypoxanthine incorporation and microscopic examination. Parasite culture treated with 10 {mu}g/ml pfHDAC-1 dsRNA exhibited 47% growth inhibition when compared with either untreated control or culture treated with an unrelated dsRNA. PfHDAC-1 dsRNA specifically blocked maturation of trophozoite to schizont stages and decreased PfHDAC-1 transcript 44% in treated trophozoites. These results indicate the potential of HDAC-1 as a target for development of novel antimalarials.
- OSTI ID:
- 21255951
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 381, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2009.01.165; PII: S0006-291X(09)00219-8; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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