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Published on: December 12, 2010
Inhibition of encystation of Entamoeba invadens by wortmannin
A Makioka1, M Kumagai, H Ohtomo
1Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan. makioka@jikei.ac.jp
Abstract:
Using an axenic encystation system in vitro, we examined the effect of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), which is a signaling molecule responsible for numerous cellular responses, on the encystation of Entamoeba invadens. Wortmannin inhibited both encystation and growth of E. invadens strain IP-1 in a dose-dependent manner, the former being more resistant to the drug than the latter. There was little decrease in the number of trophozoites after 3 days of culture in encystation medium containing wortmannin; and the cells remained motile, suggesting that the inhibitory effect of the drug on encystation was not due to its toxic effect on trophozoites. The addition of wortmannin after the induction of encystation was also inhibitory for encystation. Trophozoites incubated for 1 day in encystation medium with wortmannin did not encyst after removal of the drug, suggesting that the drug effect was not reversible in encystation medium. In contrast, trophozoites cultured in growth medium with wortmannin did encyst after their transfer to encystation medium without the drug. Encystation with wortmannin was more strongly inhibited among trophozoites grown in the presence of the drug than among those grown in the absence of the drug. The process of cyst maturation was slightly affected by wortmannin. These results suggest a possible role for PI 3-kinase in the signaling involved in the encystation of E. invadens.
Insights
Wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, significantly reduced Entamoeba invadens encystation and growth. The drug
Area of Science:
- Cell Biology
- Parasitology
- Biochemistry
Background:
- Entamoeba invadens undergoes encystation, a crucial process for its survival and transmission.
- Phosphatidylinositol 3-kinase (PI 3-kinase) is a key signaling molecule involved in various cellular functions.
- Understanding the molecular mechanisms regulating encystation is vital for developing control strategies.
Purpose of the Study:
- To investigate the role of PI 3-kinase signaling in the encystation of Entamoeba invadens.
- To determine the effect of wortmannin, a PI 3-kinase inhibitor, on E. invadens encystation and growth.
Main Methods:
- Utilized an axenic encystation system in vitro.
- Treated Entamoeba invadens strain IP-1 with varying concentrations of wortmannin.
- Assessed the impact of wortmannin on trophozoite growth, encystation rates, and cyst maturation.
Main Results:
- Wortmannin inhibited both encystation and growth of E. invadens in a dose-dependent manner.
- Encystation was more resistant to wortmannin than growth, and the drug's effect was not immediately toxic to trophozoites.
- Wortmannin treatment inhibited encystation even when applied after induction, and the effect was largely irreversible in encystation medium.
Conclusions:
- PI 3-kinase signaling appears to play a significant role in the regulation of Entamoeba invadens encystation.
- Wortmannin's inhibitory effect suggests PI 3-kinase is essential for key steps in the encystation pathway.
- Further research into PI 3-kinase's specific functions during encystation is warranted.
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