Over-expression of nm23-H1 in HeLa cells provides cells with higher resistance to oxidative stress possibly due to raising intracellular p53 and GPX1

• Published in: Acta pharmacologica Sinica Vol. 29; no. 12; pp. 1451 - 1458
• Main Authors: An, Run, Chu, Yong-lie, Tian, Chan, Dai, Xiao-xia, Chen, Jing-hong, Shi, Qi, Han, Jun, Dong, Xiao-ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2008; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Glutathione Peroxidase - genetics; Glutathione Peroxidase - metabolism; HeLa Cells; Humans; Hydrogen Peroxide - metabolism; Immunology; Internal Medicine; Medical Microbiology; NM23 Nucleoside Diphosphate Kinases - genetics; NM23 Nucleoside Diphosphate Kinases - metabolism; original-article; Oxidants - metabolism; Oxidative Stress; Pharmacology/Toxicology; Reactive Oxygen Species - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Vaccine; nm23-H1; cell viability; GPX1; oxidative stress; reactive oxygen species; p53
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2008.00902.x

Aim: To determine whether the antitumor factor nm23 is related with antioxidation. Methods: Full-length human nm23-H1 was cloned into a mammalian-expressing vector and transiently introduced into HeLa cells. Results: A remarkably low level of reactive oxygen species (ROS) was detected in the cells over-expressing 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-regulatedgene 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. Conclusion: The findings suggest that nm23-H1 may act as a cellular protector against oxidative stress, possibly triggering the p53-related antioxidative pathway.