Over-expression of nm23-H1 in HeLa cells provides cells with higher resistance to oxidative stress possibly due to raising intracellular p53 and GPX1.
OBJECTIVE
To determine whether the antitumor factor nm23 is related with antioxidation.


METHODS
Full-length human nm23-H1 was cloned into a mammalianexpressing vector and transiently introduced into HeLa cells.


RESULTS
A remarkably low level of reactive oxygen species (ROS) was detected in the cells overexpressing nm23-H1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays found that the cells transfected with a nm23- H1-expressing plasmid had higher viability and stronger resistance to oxidative stress. Immunoprecipitation tests revealed that endogenous nm23-H1 formed a protein complex with p53. Furthermore, the intracellular levels of p53 and p53- regulated gene GPX1 were obviously increased in the cells overexpressing nm23- H1. The downregulation of p53 in the cells overexpressing nm23-H1 resulted in a higher cellular ROS level and lower cell viability.


CONCLUSIONS
The findings suggest that nm23-H1 may act as a cellular protector against oxidative stress, possibly triggering the p53-related antioxidative pathway.
An
Run
R
School of Medicine, Xi'an Jiao-Tong University, Xi'an 710061, China.
Chu
Yong-lie
YL
Tian
Chan
C
Dai
Xiao-xia
XX
Chen
Jing-hong
JH
Shi
Qi
Q
Han
Jun
J
Dong
Xiao-ping
XP
D000818:Animals; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
D054778:NM23 Nucleoside Diphosphate Kinases; D016877:Oxidants; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; C517938:NME1 protein, human; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human