- Morphological changes in human gastric epithelial cells induced by nuclear targeting of Helicobacter pylori urease subunit A
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Jung Hwa Lee , So Hyun Jun , Jung-Min Kim , Seung Chul Baik , Je Chul Lee
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J. Microbiol. 2015;53(6):406-414. Published online May 30, 2015
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DOI: https://doi.org/10.1007/s12275-015-5085-5
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Nuclear targeting of bacterial proteins and their pathological
effects on host cells are an emerging pathogenic mechanism
in bacteria. We have previously reported that urease subunit
A (UreA) of Helicobacter pylori targets the nuclei of COS-7
cells through nuclear localization signals (NLSs). This study
further investigated whether UreA of H. pylori targets the
nuclei of gastric epithelial cells and then induces molecular
and cellular changes in the host cells. H. pylori 26695 strain
produced and secreted outer membrane vesicles (OMVs).
UreA was translocated into gastric epithelial AGS cells through
outer membrane vesicles (OMVs) and then targeted the nuclei
of AGS cells. Nuclear targeting of rUreA did not induce
host cell death, but resulted in morphological changes, such
as cellular elongation, in AGS cells. In contrast, AGS cells
treated with rUreAΔNLS proteins did not show this morphological
change. Next generation sequencing revealed that
nuclear targeting of UreA differentially regulated 102 morphogenesis-
related genes, of which 67 and 35 were up-regulated
and down-regulated, respectively. Our results suggest
that nuclear targeting of H. pylori UreA induces both molecular
and cellular changes in gastric epithelial cells.
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Citations
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- Helicobacter pylori γ-Glutamyltranspeptidase Induces Cell Cycle Arrest at the G1-S Phase Transition
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Kyung-Mi Kim , Seung-Gyu Lee , Jung-Min Kim , Do-Su Kim , Jea-Young Song , Hyung-Lyun Kang , Woo-Kon Lee , Myung-Je Cho , Kwang-Ho Rhee , Hee-Shang Youn , Seung-Chul Baik
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J. Microbiol. 2010;48(3):372-377. Published online June 23, 2010
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DOI: https://doi.org/10.1007/s12275-010-9293-8
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In our previous study, we showed that Helicobacter pylori γ-glutamyltranspeptidase (GGT) is associated with H. pylori-induced apoptosis through a mitochondrial pathway. To better understand the role of GGT in apoptosis, we examined the effect of GGT on cell cycle regulation in AGS cells. To determine the effect of recombinant GGT (rGGT) on cell cycle distribution and apoptosis, rGGT-treated and untreated AGS cells were analyzed in parallel by flow cytometry using propidium iodide (PI). We found that rGGT inhibited the growth of AGS cells in a time-dependent manner, and that the pre-exposure of cells to a caspase-3 inhibitor (z-DEVD-fmk) effectively blocked GGT-induced apoptosis. Cell cycle analysis showed G1 phase arrest and apoptosis in AGS cells following rGGT treatment. The rGGT-mediated G1 phase arrest was found to be associated with down-regulation of cyclin E, cyclin A, Cdk 4, and Cdk 6, and the up-regulation of the cyclindependent kinase (Cdk) inhibitors p27 and p21. Our results suggest that H. pylori GGT induces cell cycle arrest at the G1-S phase transition.
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