title: Inhibition of Plasmodium falciparum proliferation in vitro by double-stranded RNA directed against malaria histone deacetylase.
abstract: 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 microg of dsRNA/ml of culture for 48 h and growth was determined by [3H]-hypoxanthine incorporation and microscopic examination. Parasite culture treated with 10 microg/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.
authors.affiliation: Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Sriwilaijaroen
authors.forename: S
authors.initials: S
authors.lastname: Boonma
authors.forename: P
authors.initials: P
authors.lastname: Attasart
authors.forename: J
authors.initials: J
authors.lastname: Pothikasikorn
authors.forename: S
authors.initials: S
authors.lastname: Panyim
authors.forename: W
authors.initials: W
authors.lastname: Noonpakdee