O-deGlcNAcylation is required for <i>Entamoeba histolytica</i>-induced HepG2 cell death

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P> <I>Entamoeba histolytica</I> is an enteric tissue-invading protozoan parasite that causes amoebic colitis and occasionally liver abscess in humans. <I>E. histolytica</I> can induce host-cell apoptosis by initiating various intracellular signaling mechanisms closely associated with tissue pathogenesis and parasitic immune evasion. O-GlcNAcylation, similar to phosphorylation, is involved in various cell-signaling processes, including apoptosis and proliferation, with O-GlcNAc addition and removal regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. However, whether O-GlcNAc alterations in host cells affect <I>E. histolytica</I>-induced cell death and which signal molecules participate in <I>E. histolytica</I>-induced deglycosylation remain unknown. In this study, co-incubation of HepG2 cells with <I>E. histolytica</I> increased DNA fragmentation and LDH release as compared with control cells. Additionally, Gal-lectin-mediated amoebic adherence of live trophozoites to HepG2 cells decreased O-GlcNAcylated protein levels within 5 min. We also observed a rapid decrease in cellular OGT protein level, but not OGA, in HepG2 cells in a contact-dependent manner. Furthermore, HepG2 pretreatment with OGA inhibitors or OGA siRNA prevented <I>E. histolytica</I>-induced O-deGlcNAcylation, DNA fragmentation, and LDH release. Our results suggested that <I>E. histolytica</I>-induced O-deGlcNAcylation in HepG2 cells was an important process required for hepatocyte cell death induced by <I>E. histolytica</I> adherence.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Entamoeba histolytica</I> remarkably induces cell death in HepG2 cells. </LI> <LI> O-GlcNAcylated proteins were rapidly and dramatically reduced in Entamoeba-treated HepG2 cells in a contact-dependent manner. </LI> <LI> Alteration of OGT/OGA expression with OGA inhibitor reduces <I>E. histolytica</I>-induced O-deGlcNAcylation in HepG2 cells. </LI> <LI> Inhibition of OGA activity reduces <I>Entamoeba</I>-induced host cell death in HepG2 cells. </LI> </UL> </P>