Helicobacter pylori gamma-glutamyltranspeptidase induces cell cycle arrest at the G1-S phase transition.
In our previous study, we showed that Helicobacter pylori gamma-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 cyclin-dependent kinase (Cdk) inhibitors p27 and p21. Our results suggest that H. pylori GGT induces cell cycle arrest at the G1-S phase transition.
Kim
Kyung-Mi
KM
Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, 660-751, Republic of Korea.
Lee
Seung-Gyu
SG
Kim
Jung-Min
JM
Kim
Do-Su
DS
Song
Jea-Young
JY
Kang
Hyung-Lyun
HL
Lee
Woo-Kon
WK
Cho
Myung-Je
MJ
Rhee
Kwang-Ho
KH
Youn
Hee-Shang
HS
Baik
Seung-Chul
SC
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity*; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D005723:gamma-Glutamyltransferase / Q000494:pharmacology / Q000502:physiology*
D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D005723:gamma-Glutamyltransferase