Dual effect of oxidative stress on NF-kappaB activation in HeLa cells.
- Author:
Mi Sun BYUN
1
;
Kye Im JEON
;
Jae Won CHOI
;
Jae Yong SHIM
;
Dae Myung JUE
Author Information
1. Department of Biochemostry, College of Medicine, The Catholic University of Korea, Seoul, Korea. dmjue@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
NF-kappaB;
oxidative stress;
hydrogen peroxide;
diamide;
protein kinases;
oxidation-reduction
- MeSH:
Cell Nucleus/drug effects/metabolism;
Cytosol/drug effects/metabolism;
Diamide/pharmacology;
Hela Cells/drug effects/metabolism;
Human;
Hydrogen Peroxide/pharmacology;
I-kappa B/drug effects/metabolism;
NF-kappa B/drug effects/genetics/*metabolism;
Oxidants/pharmacology;
*Oxidative Stress;
Protein-Serine-Threonine Kinases/metabolism;
Signal Transduction/drug effects;
Time Factors;
Transcription, Genetic;
Tumor Necrosis Factor/pharmacology
- From:Experimental & Molecular Medicine
2002;34(5):332-339
- CountryRepublic of Korea
- Language:English
-
Abstract:
Reactive oxygen species (ROS) has been implicated as an inducer of NF-kappaB activity in numbers of cell types where exposure of cells to ROS such as H2O2 leads to NF-kappaB activation. In contrast, exposure to oxidative stress in certain cell types induced reduction of tumor necrosis factor (TNF)-induced NF-kappaB activation. And various thiol-modifying agents including gold compounds and cyclopentenone prostaglandins inhibit NF-kappaB activation by blocking IkappaB kinase (IKK). To understand such conflicting effect of oxidative stress on NF-kappaB activation, HeLa cells were incubated with H2O2 or diamide and TNF-induced expression of NF-kappaB reporter gene was measured. NF-kappaB activation was significantly blocked by these oxidizing agents, and the inhibition was accompanied with reduced nuclear NF-kappaB and inappropriate cytosolic IkappaB degradation. H2O2 and diamide also inhibited IKK activation in HeLa and RAW 264.7 cells stimulated with TNF and lipopolysaccharide, respectively, and directly blocked IKK activity in vitro. In cells treated with H2O2 alone, nuclear NF-kappaB was induced after 2 h without detectible degradation of cytosolic IkBa or activation of IKK. Our results suggest that ROS has a dual effect on NF-kappaB activation in the same HeLa cells: it inhibits acute IKK-mediated NF-kappaB activation induced by inflammatory signals, while longer-term exposure to ROS induces NF-kappaB activity through an IKK-independent pathway.
