title: Amoebic PI3K and PKC is required for Jurkat T cell death induced by Entamoeba histolytica.
abstract: The enteric protozoan parasite Entamoeba histolytica is the causative agent of human amebiasis. During infection, adherence of E. histolytica through Gal/GalNAc lectin on the surface of the amoeba can induce caspase-3-dependent or -independent host cell death. Phosphorylinositol 3-kinase (PI3K) and protein kinase C (PKC) in E. histolytica play an important function in the adhesion, killing, or phagocytosis of target cells. In this study, we examined the role of amoebic PI3K and PKC in amoeba-induced apoptotic cell death in Jurkat T cells. When Jurkat T cells were incubated with E. histolytica trophozoites, phosphatidylserine (PS) externalization and DNA fragmentation in Jurkat cells were markedly increased compared to those of cells incubated with medium alone. However, when amoebae were pretreated with a PI3K inhibitor, wortmannin before being incubated with E. histolytica, E. histolytica-induced PS externalization and DNA fragmentation in Jurkat cells were significantly reduced compared to results for amoebae pretreated with DMSO. In addition, pretreatment of amoebae with a PKC inhibitor, staurosporine strongly inhibited Jurkat T cell death. However, E. histolytica-induced cleavage of caspase-3, -6, and -7 were not inhibited by pretreatment of amoebae with wortmannin or staurosporin. In addition, we found that amoebic PI3K and PKC have an important role on amoeba adhesion to host compartment. These results suggest that amebic PI3K and PKC activation may play an important role in caspase-independent cell death in Entamoeba-induced apoptosis.
authors.affiliation: Department of Environmental Medical Biology and Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Lee
authors.affiliation: Department of Environmental Medical Biology and Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Kyeong Ah
authors.initials: KA
authors.lastname: Kim
authors.affiliation: Department of Environmental Medical Biology and Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Arim
authors.initials: A
authors.lastname: Min
authors.affiliation: Department of Environmental Medical Biology and Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Myeong Heon
authors.initials: MH
authors.lastname: Shin
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000254:growth & development*; D006801:Humans; D006868:Hydrolysis; D019169:Jurkat Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D013601:T-Lymphocytes / Q000469:parasitology* / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020169:Caspases
keywords: Entamoeba histolytica; adhesion; caspase; host cell death; phosphorylinositol 3-kinase (PI3K); protein kinase C (PKC)