Degradation of the Transcription Factors NF-κB, STAT3, and STAT5 Is Involved in Entamoeba histolytica-Induced Cell Death in Caco-2 Colonic Epithelial Cells
| Autor: | Arim Min, Young Ah Lee, Myeong Heon Shin, Kyeong Ah Kim |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
STAT3 Transcription Factor
Programmed cell death Necrosis Colon NF-κB Entamoeba histolytica parasitic diseases STAT5 Transcription Factor medicine Humans Intestinal Mucosa RNA Small Interfering STAT3 STAT5 Caspase Cell Death biology Calpain Caspase 3 STAT Calcium-Binding Proteins NF-kappa B Epithelial Cells Caco-2 biology.organism_classification Molecular biology digestive system diseases Cell biology Infectious Diseases Apoptosis Caspases biology.protein I-kappa B Proteins RNA Interference Original Article Parasitology Caco-2 Cells m-calpain medicine.symptom Signal Transduction |
| Zdroj: | The Korean Journal of Parasitology |
| ISSN: | 1738-0006 |
| DOI: | 10.3347/kjp.2014.52.5.459 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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