Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/95689
Title: Comparative gene expression profiling of P. falciparum malaria parasites exposed to three different histone deacetylase inhibitors
Authors: Andrews, Katherine T.
Gupta, Archna P.
Tran, Thanh N.
Fairlie, David P.
Gobert, Geoffrey N.
Bozdech, Zbynek
Keywords: DRNTU::Science::Biological sciences::Microbiology
Issue Date: 2012
Source: Andrews, K. T., Gupta, A. P., Tran, T. N., Fairlie, D. P., Gobert, G. N., & Bozdech, Z. (2012). Comparative Gene Expression Profiling of P. falciparum Malaria Parasites Exposed to Three Different Histone Deacetylase Inhibitors. PLoS ONE, 7(2).
Series/Report no.: PLoS ONE
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; Vorinostat®) 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 culturing for a further 2 h. Despite some structural similarity, the three inhibitors caused quite diverse transcriptional effects, possibly reflecting subtle differences in mode of action or cellular distribution. This dataset represents an important contribution to our understanding of how HDAC inhibitors act on malaria parasites and identifies alpha tubulin II as a potential transcriptional marker of HDAC inhibition in malaria parasites that may be able to be exploited for future development of HDAC inhibitors as new antimalarial agents.
URI: https://hdl.handle.net/10356/95689
http://hdl.handle.net/10220/9369
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0031847
Schools: School of Biological Sciences 
Rights: © 2012 The Authors.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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