title: Involvement of p38MAPK-ATF2 signaling pathway in alternariol induced DNA polymerase β expression.
abstract: Base excision repair (BER) systems are important for maintaining the integrity of genomes in mammalian cells. Aberrant DNA bases or broken single strands can be repaired by BER. Consequently, DNA lesions, which may be caused by cancer and aging, have a close association with BER procedure. DNA polymerase β (polβ) is a critical BER enzyme that can excise 5'-sugar phosphate prior to adding a nucleotide in the gap by its function as a DNA polymerase in the BER process. However, DNA polβ is an error-prone DNA polymerase, and overexpressing polβ increases the cellular spontaneous mutation rate. DNA polβ overexpression has been identified in various human tumors, which implies that DNA polβ overexpression has a close association with tumorigenesis. The present study showed that alternariol (AOH), a secondary product of a fungus that is found in grains and fruits, could cause DNA damage to NIH3T3 cells in a single cell gel electrophoresis, and that 2, 10 and 20 µM AOH induced DNA polβ overexpression in a dose-dependent manner. In the process, the level of phosphorylation of mitogen-activated protein kinase 14 (p38) mitogen-activated protein kinase (MAPK) and activating transcription factor 2 (ATF2) was increased. In addition, SB203580, a p38MAPK inhibitor, resulted in decreased DNA polβ expression. Small hairpin RNA-p38MAPK had the same effect; notably, DNA polβ expression was downregulated in p38MAPK knockdown cells. These data suggest that the p38MAPK-ATF2 signaling pathway may be involved in DNA polβ expression induced by AOH.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Junfen
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Changzhi People's Hospital, Changzhi, Shanxi 046000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Youtian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Kangdong
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
keywords: DNA polymerase β; activating transcription factor 2; alternariol; mitogen-activated protein kinase 14 mitogen-activated protein kinase