ERK and p38 MAPK signaling pathways are involved in ochratoxin A-induced G2 phase arrest in human gastric epithelium cells.
Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic, and immunotoxic effects. Recent work from our laboratory found that OTA evoked G2 phase arrest in GES-1 cells in vitro by modulating the key factors Cdc25C, Cdc2 and cyclinB1, which were critical to the G2/M phase transmission, suggested that OTA-induced G2 arrest mediate at least in part OTA toxicity effect. However, the molecular mechanism of this effect is currently unclear. In the present study, we showed that treatment of GES-1 cells with OTA could induce the activation of MAPK family members ERK and p38. ERK inhibitor PD98059 and p38 inhibitor SB203580 significantly reversed the depression of Cdc25C/p-Cdc25C, Cdc2/p-Cdc2, cyclinB1 as well as the cyclinB1-Cdc2 complex, thereby, abolished the delay in G2 phase. In addition, silencing ERK and p38 expression with siRNA significantly inhibited OTA-induced G2 arrest in GES-1 cells as well. Collectively, these data suggest that the ERK and p38 MAPK signaling pathways play important roles in the regulation of OTA-induced G2 arrest in GES-1 cells.
Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China.
Yuan
Y
Wang
Jing
J
Liu
Jinfeng
J
Cui
Lingxiao
L
Xing
Junling
J
Wang
Xia
X
Yan
Xianghong
X
Zhang
D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009793:Ochratoxins / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005419:Flavonoids; D009793:Ochratoxins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C025589:ochratoxin A; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one