| 19094990 |
Azzi A, Cosseau C, Grunau C: Schistosoma mansoni: developmental arrest of miracidia treated with histone deacetylase inhibitors. Exp Parasitol. 2009 Mar;121(3):288-91. Epub 2008 Dec 6.
In the present study, we examined the effect of the histone deacetylase (HDAC) inhibitors trichostatin A (TSA), valproic acid (VA) and sodium-butyrate on the metamorphosis of larvae of the human blood-fluke Schistosoma mansoni from the free-swimming miracidia into the intramolluskal sporocyst. We show that HDAC inhibitors block transformation in concentration dependant manner. TSA reversibly blocks this developmental process: only 13+/-11% of TSA treated miracidia transform into sporocysts in-vitro, compared to 92+/-3% in the mock-treated control. Other enzyme inhibitors such as cycloheximide or hydroxyurea had no effect on metamorphosis. For treatment of up to 4 h, the effect of TSA was completely reversible. Our data indicates that HDAC activity is necessary for the transformation of S. mansoni miracidia during infection of the snail host. |
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