Trichostatin A regulates peroxiredoxin expression and virulence of the parasite Entamoeba histolytica.
Histone deacetylation is associated with a repressed chromatin state, and histone acetylase and deacetylase activities have been previously described in Entamoeba histolytica. To investigate their roles in the control of Entamoeba gene expression, the parasite was grown in 50 nM trichostatin A (TSA), an inhibitor of histone deacetylase. TSA enhanced the cytopathic and hemolytic activity of the parasite and its resistance to oxidative stress. We first focused our attention on peroxiredoxin, a protein previously associated with E. histolytica virulence and resistance to oxidative stress. We found that the expression of peroxiredoxin was increased after TSA treatment, but were unable to confirm that this was a direct consequence of histone modification at the promoter. By microarray analysis, we found that some other mRNAs encoding some other virulence factors, such as the galactose-inhibitable lectin small subunits, were also increased. The pattern of gene expression was surprisingly different from that previously described after treatment with 150 nM TSA.
Isakov
Elada
E
Department of Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, Haifa, Israel.
Siman-Tov
Rama
R
Weber
Christian
C
Guillen
Nancy
N
Ankri
Serge
S
D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D002470:Cell Survival; D004748:Entamoeba histolytica / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000469:parasitology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006461:Hemolysis; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D037102:Lectins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000096:biosynthesis*; D015800:Protozoan Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
D000982:Antipruritics; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D037102:Lectins; D016877:Oxidants; D015800:Protozoan Proteins; D037521:Virulence Factors; C078014:N-acetylgalactosamine inhibitable lectin 35-kDa subunit, Entamoeba histolytica; C012589:trichostatin A; D054464:Peroxiredoxins