Decreased O-glycosylation level is closely involved in cell death of human hepatocytes induced by tissue-invading protozoan parasite Entamoeba histolytica
Young Ah Lee, Arim Min, Young Hee Nam, David Mirelman, Jin Won Cho, Myeong Heon Shin
언어
영어(ENG)
URL
https://www.earticle.net/Article/A192933
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원문정보
초록
영어
Entamoeba histolytica is anenteric tissue-invasion protozoan parasite that causes amoebic colitis and occasionally liver abscess in humans. E. histolytica can induce host cell apoptosis by the induction of various intracellular signal mechanisms. These modulations triggered by E. histolytica are closely associated with tissue pathogenesis and parasitic immune evasion mechanism. O-GlcNAcyation, similar to phosphorylation, has been thought to contribute the various cellular signal processes including apoptosis and proliferation. However, it is unknown whether E. histolytica can affect the O-GlcNAc level in host cells during Entamoeba-induced cell death. In this study, we investigated whether modulation of O-GlcNAcylated protein levels in host cells is involved in HepG2 cell death induced by E. histolytica using virulent strain HM-1 and non-virulent Rahman. Co-incubation of HepG2 cells with HM-1 strain remarkably increased DNA fragmentation and LDH release compared to cells incubated with Rahman strain or medium alone. In addition, Entamoeba HM-1induced tyrosine dephosphorylation, and activation of caspases-3 and calpain in HepG2 cells. Gal-lectin-mediated amoebic adherence of live HM-1 trophozoites to the HepG2 cells decreased of O-GlcNAcylated protein levels in HepG2 cells within 2 min, while non-virulent Rahman strain did not. Indeed, E. histolytica-induced deGlcNAcylation in HepG2 cells was prevented by O-GlcNAcase inhibitors, PUGNAc or Thi-Met G. In addition, DNA fragmentation and LDH release triggered by E. histolytica HM-1 were strongly inhibited by pretreatment of host cells with OGA inhibitor PUGNAc. Our results suggest that decreased O-glycosylation is required for cell death in hepatocytes induced by adherence of E. histolytica.
저자
Young Ah Lee [ Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ]
Arim Min [ Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ]
Young Hee Nam [ Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ]
David Mirelman [ Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel ]
Jin Won Cho [ Department of Integrated OMICS for Biomedical Science and Systems Biology, Yonsei University, Seoul, 120-749, Korea ]
Myeong Heon Shin [ Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.