comparative gene expression profiling of p. falciparum malaria parasites exposed to three different histone deacetylase inhibitors比较基因表达分析的恶性疟原虫疟疾寄生虫暴露在三个不同的组蛋白脱乙酰酶抑制剂.pdf

Comparative Gene Expression Profiling of P. falciparum Malaria Parasites Exposed to Three Different Histone Deacetylase Inhibitors 1,2 3 1,2 4 2 Katherine T. Andrews *, Archna P. Gupta , Thanh N. Tran , David P. Fairlie , Geoffrey N. Gobert , Zbynek Bozdech3 1 Eskitis Institute for Cell and Molecular Therapies, Griffith University, Queensland, Australia, 2 Queensland Institute of Medical Research, Queensland, Australia, 3 School of Biological Sciences, Nanyang Technological University, Singapore, Singapore, 4 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia Abstract Histone deacetylase (HDAC) inhibitors are being intensively pursued as potential new drugs for a range of diseases, including malaria. HDAC inhibitors are also important tools for the study of epigenetic mechanisms, transcriptional control, and other important cellular processes. In this study the effects of three structurally related antimalarial HDAC inhibitors on P. falciparum malaria parasite gene expression were compared. The three hydroxamate-based compounds, trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA; VorinostatH) and a 2-aminosuberic acid derivative (2-ASA-9), all caused profound transcriptional effects, with ,2–21% of genes having .2-fold altered expression following 2 h exposure to the compounds. Only two genes, alpha tubulin II and a hydrolase, were up-regulated by all three compounds after 2 h exposure in all biological replicates examined. The transcriptional changes observed after 2 h exposure to HDAC inhibitors were found to be largely transitory, with only 1–5% of genes being regulated after removing the compounds and culturi