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Degradation of the transcription factors NF-kB, STAT3, and STAT5 is involved in Entamoeba histolytica-induced cell death in Caco-2 colonic epithelial cells

 Kyeong Ah Kim  ;  Arim Min  ;  Young Ah Lee  ;  Myeong Heon Shin 
 KOREAN JOURNAL OF PARASITOLOGY, Vol.52(5) : 459-469, 2014 
Journal Title
Issue Date
Caco-2 Cells ; Calcium-Binding Proteins ; Calpain/genetics ; Calpain/metabolism ; Caspase 3/genetics ; Caspase 3/metabolism ; Caspases ; Cell Death* ; Colon/cytology ; Entamoeba histolytica/physiology* ; Epithelial Cells/cytology ; Epithelial Cells/parasitology ; Humans ; I-kappa B Proteins/metabolism ; Intestinal Mucosa/cytology ; NF-kappa B/genetics ; NF-kappa B/metabolism* ; RNA Interference ; RNA, Small Interfering ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism* ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism* ; Signal Transduction
Caco-2 ; Entamoeba histolytica ; NF-κB ; STAT ; m-calpain
Entamoeba histolytica is a tissue-invasive protozoan parasite causing dysentery in humans. During infection of colonic tissues, amoebic trophozoites are able to kill host cells via apoptosis or necrosis, both of which trigger IL-8-mediated acute inflammatory responses. However, the signaling pathways involved in host cell death induced by E. histolytica have not yet been fully defined. In this study, we examined whether calpain plays a role in the cleavage of pro-survival transcription factors during cell death of colonic epithelial cells, induced by live E. histolytica trophozoites. Incubation with amoebic trophozoites induced activation of m-calpain in a time- and dose-dependent manner. Moreover, incubation with amoebae resulted in marked degradation of STAT proteins (STAT3 and STAT5) and NF-κB (p65) in Caco-2 cells. However, IκB, an inhibitor of NF-κB, was not cleaved in Caco-2 cells following adherence of E. histolytica. Entamoeba-induced cleavage of STAT proteins and NF-κB was partially inhibited by pretreatment of cells with a cell-permeable calpain inhibitor, calpeptin. In contrast, E. histolytica did not induce cleavage of caspase-3 in Caco-2 cells. Furthermore, pretreatment of Caco-2 cells with a calpain inhibitor, calpeptin (but not the pan-caspase inhibitor, z-VAD-fmk) or m-calpain siRNA partially reduced Entamoeba-induced DNA fragmentation in Caco-2 cells. These results suggest that calpain plays an important role in E. histolytica-induced degradation of NF-κB and STATs in colonic epithelial cells, which ultimately accelerates cell death.
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1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Ah(김경아)
Min, A Rim(민아림) ORCID logo https://orcid.org/0000-0003-2938-9630
Shin, Myeong Heon(신명헌) ORCID logo https://orcid.org/0000-0001-8207-6110
Lee, Young Ah(이영아) ORCID logo https://orcid.org/0000-0002-0414-842X
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