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(The FASEB Journal. 1999;13:1137-1143.)
© 1999 FASEB

Is NF-{kappa}B the sensor of oxidative stress?

NANXIN LI1 and MICHAEL KARIN1

Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0636, USA

1Correspondence: Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0636, USA. E-mail: karinoffice{at}ucsd.edu

NF-{kappa}B is a dimeric transcription factor that is involved in the regulation of a large number of genes that control various aspects of the immune and inflammatory response. It is activated by a variety of stimuli ranging from cytokines, to various forms of radiation, to oxidative stress (such as exposure to H2O2). Recent studies have advanced our understanding of the signal transduction pathway leading to NF-{kappa}B activation by cytokines and will provide insights for the mechanism by which NF-{kappa}B is regulated by oxidative stress. An important question that is yet to be answered is whether reactive oxygen species play a physiological role in NF-{kappa}B activation.—Li, N., Karin, M. Is NF-{kappa}B the sensor of oxidative stress?


Key Words: I{kappa}B degradation • IKK • reactive oxygen species • tumor necrosis factor • GSH




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N. Sugino, A. Karube-Harada, A. Sakata, S. Takiguchi, and H. Kato
Nuclear Factor-{kappa}B Is Required for Tumor Necrosis Factor-{alpha}-Induced Manganese Superoxide Dismutase Expression in Human Endometrial Stromal Cells
J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3845 - 3850.
[Abstract] [Full Text] [PDF]


Home page
Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
D. Hamerman
Molecular-Based Therapeutic Approaches in Treatment of Anorexia of Aging and Cancer Cachexia
J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2002; 57(8): M511 - 518.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
P. Gergely Jr., B. Niland, N. Gonchoroff, R. Pullmann Jr., P. E. Phillips, and A. Perl
Persistent Mitochondrial Hyperpolarization, Increased Reactive Oxygen Intermediate Production, and Cytoplasmic Alkalinization Characterize Altered IL-10 Signaling in Patients with Systemic Lupus Erythematosus
J. Immunol., July 15, 2002; 169(2): 1092 - 1101.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
A. Masamune, K. Kikuta, M. Satoh, A. Satoh, and T. Shimosegawa
Alcohol Activates Activator Protein-1 and Mitogen-Activated Protein Kinases in Rat Pancreatic Stellate Cells
J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 36 - 42.
[Abstract] [Full Text] [PDF]


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Hum ReprodHome page
N. Sugino, A. Karube-Harada, A. Sakata, S. Takiguchi, and H. Kato
Different mechanisms for the induction of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone in human endometrial stromal cells
Hum. Reprod., July 1, 2002; 17(7): 1709 - 1714.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
K. N. Islam and C. R. Mendelson
Potential Role of Nuclear Factor {kappa}B and Reactive Oxygen Species in cAMP and Cytokine Regulation of Surfactant Protein-A Gene Expression in Lung Type II Cells
Mol. Endocrinol., June 1, 2002; 16(6): 1428 - 1440.
[Abstract] [Full Text] [PDF]


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Am. J. Respir. Cell Mol. Bio.Home page
I. Kosmidou, T. Vassilakopoulos, A. Xagorari, S. Zakynthinos, A. Papapetropoulos, and C. Roussos
Production of Interleukin-6 by Skeletal Myotubes . Role of Reactive Oxygen Species
Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 587 - 593.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
M. Rodriguez-Porcel, L. O Lerman, D. R Holmes Jr., D. Richardson, C. Napoli, and A. Lerman
Chronic antioxidant supplementation attenuates nuclear factor-{kappa}B activation and preserves endothelial function in hypercholesterolemic pigs
Cardiovasc Res, March 1, 2002; 53(4): 1010 - 1018.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
C. Weiss, A. Bierhaus, R. Kinscherf, V. Hack, T. Luther, P. P. Nawroth, and P. Bartsch
Tissue factor-dependent pathway is not involved in exercise-induced formation of thrombin and fibrin
J Appl Physiol, January 1, 2002; 92(1): 211 - 218.
[Abstract] [Full Text] [PDF]


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Physiol. Rev.Home page
W. Droge
Free Radicals in the Physiological Control of Cell Function
Physiol Rev, January 1, 2002; 82(1): 47 - 95.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y.-W. Mao, H. Xiang, J. Wang, S. Korsmeyer, J. Reddan, and D. W.-C. Li
Human bcl-2 Gene Attenuates the Ability of Rabbit Lens Epithelial Cells against H2O2-induced Apoptosis through Down-regulation of the alpha B-crystallin Gene
J. Biol. Chem., November 9, 2001; 276(46): 43435 - 43445.
[Abstract] [Full Text] [PDF]


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Mol. Pharmacol.Home page
H. Kim, T.-H. Lee, Y. S. Hwang, M. A. Bang, K. H. Kim, J. M. Suh, H. K. Chung, D.-Y. Yu, K.-K. Lee, O-Y. Kwon, et al.
Methimazole As an Antioxidant and Immunomodulator in Thyroid Cells: Mechanisms Involving Interferon-gamma Signaling and H2O2 Scavenging
Mol. Pharmacol., November 1, 2001; 60(5): 972 - 980.
[Abstract] [Full Text] [PDF]


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GutHome page
T Y Oh, J S Lee, B O Ahn, H Cho, W B Kim, Y B Kim, Y J Surh, S W Cho, K M Lee, and K B Hahm
Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats
Gut, September 1, 2001; 49(3): 364 - 371.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
G. Valen, Z.-q. Yan, and G.o. K. Hansson
Nuclear factor kappa-B and the heart
J. Am. Coll. Cardiol., August 1, 2001; 38(2): 307 - 314.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
G. Gong, G. Waris, R. Tanveer, and A. Siddiqui
Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B
PNAS, July 24, 2001; (2001) 171311298.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
X. Zou, T. Tsutsui, D. Ray, J. F. Blomquist, H. Ichijo, D. S. Ucker, and H. Kiyokawa
The Cell Cycle-Regulatory CDC25A Phosphatase Inhibits Apoptosis Signal-Regulating Kinase 1
Mol. Cell. Biol., July 15, 2001; 21(14): 4818 - 4828.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
M. Yoshida, T. R. Korfhagen, and J. A. Whitsett
Surfactant Protein D Regulates NF-{{kappa}}B and Matrix Metalloproteinase Production in Alveolar Macrophages via Oxidant-Sensitive Pathways
J. Immunol., June 15, 2001; 166(12): 7514 - 7519.
[Abstract] [Full Text] [PDF]


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Am. J. Respir. Cell Mol. Bio.Home page
I. Jaspers, W. Zhang, A. Fraser, J. M. Samet, and W. Reed
Hydrogen Peroxide Has Opposing Effects on IKK Activity and Ikappa Balpha Breakdown in Airway Epithelial Cells
Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 769 - 777.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
C.-H. Yeh, L. Sturgis, J. Haidacher, X.-N. Zhang, S. J. Sherwood, R. J. Bjercke, O. Juhasz, M. T. Crow, R. G. Tilton, and L. Denner
Requirement for p38 and p44/p42 Mitogen-Activated Protein Kinases in RAGE-Mediated Nuclear Factor-{kappa}B Transcriptional Activation and Cytokine Secretion
Diabetes, June 1, 2001; 50(6): 1495 - 1504.
[Abstract] [Full Text]


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J. Leukoc. Biol.Home page
M. D. Wheeler, S. Yamashina, M. Froh, I. Rusyn, and R. G. Thurman
Adenoviral gene delivery can inactivate Kupffer cells: role of oxidants in NF-{kappa}B activation and cytokine production
J. Leukoc. Biol., April 1, 2001; 69(4): 622 - 630.
[Abstract] [Full Text]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
I. Kosmidou, A. Xagorari, C. Roussos, and A. Papapetropoulos
Reactive oxygen species stimulate VEGF production from C2C12 skeletal myotubes through a PI3K/Akt pathway
Am J Physiol Lung Cell Mol Physiol, April 1, 2001; 280(4): L585 - L592.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
T.-S. Lee and L.-Y. Chau
Fas/Fas ligand-mediated death pathway is involved in oxLDL-induced apoptosis in vascular smooth muscle cells
Am J Physiol Cell Physiol, March 1, 2001; 280(3): C709 - C718.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
P.a. Aukrust, R. K. Berge, T. Ueland, E. Aaser, J. K. Damas, L. Wikeby, A. Brunsvig, F. Muller, K. Forfang, S. S. Froland, et al.
Interaction between chemokines and oxidative stress: possible pathogenic role in acute coronary syndromes
J. Am. Coll. Cardiol., February 1, 2001; 37(2): 485 - 491.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
E. Abraham, J. Arcaroli, and R. Shenkar
Activation of Extracellular Signal-Regulated Kinases, NF-{{kappa}}B, and Cyclic Adenosine 5'-Monophosphate Response Element-Binding Protein in Lung Neutrophils Occurs by Differing Mechanisms After Hemorrhage or Endotoxemia
J. Immunol., January 1, 2001; 166(1): 522 - 530.
[Abstract] [Full Text] [PDF]


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J. Nutr.Home page
P. I. Oteiza, M. S. Clegg, and C. L. Keen
Short-Term Zinc Deficiency Affects Nuclear Factor-{{kappa}}B Nuclear Binding Activity in Rat Testes
J. Nutr., January 1, 2001; 131(1): 21 - 26.
[Abstract] [Full Text]


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Plant CellHome page
M. L. Orozco-Cárdenas, J. Narváez-Vásquez, and C. A. Ryan
Hydrogen Peroxide Acts as a Second Messenger for the Induction of Defense Genes in Tomato Plants in Response to Wounding, Systemin, and Methyl Jasmonate
PLANT CELL, January 1, 2001; 13(1): 179 - 191.
[Abstract] [Full Text]


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J. Immunol.Home page
A. G. Bowie and L. A. J. O'Neill
Vitamin C Inhibits NF-{kappa}B Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase
J. Immunol., December 15, 2000; 165(12): 7180 - 7188.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. J. Thannickal and B. L. Fanburg
Reactive oxygen species in cell signaling
Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1005 - L1028.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. Hortelano, A. Castrillo, A. M. Alvarez, and L. Bosca
Contribution of Cyclopentenone Prostaglandins to the Resolution of Inflammation Through the Potentiation of Apoptosis in Activated Macrophages
J. Immunol., December 1, 2000; 165(11): 6525 - 6531.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. K. Manna, A. Mukhopadhyay, and B. B. Aggarwal
Leflunomide Suppresses TNF-Induced Cellular Responses: Effects on NF-{kappa}B, Activator Protein-1, c-Jun N-Terminal Protein Kinase, and Apoptosis
J. Immunol., November 15, 2000; 165(10): 5962 - 5969.
[Abstract] [Full Text] [PDF]


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BloodHome page
A. Khajuria and D. S. Houston
Induction of monocyte tissue factor expression by homocysteine: a possible mechanism for thrombosis
Blood, August 1, 2000; 96(3): 966 - 972.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
N. S. Chandel, W. C. Trzyna, D. S. McClintock, and P. T. Schumacker
Role of Oxidants in NF-{kappa}B Activation and TNF-{alpha} Gene Transcription Induced by Hypoxia and Endotoxin
J. Immunol., July 15, 2000; 165(2): 1013 - 1021.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
M. Holmes-McNary and A. S. Baldwin Jr.
Chemopreventive Properties of trans-Resveratrol Are Associated with Inhibition of Activation of the I{{kappa}}B Kinase
Cancer Res., July 1, 2000; 60(13): 3477 - 3483.
[Abstract] [Full Text]


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Cancer Res.Home page
S. K. Manna, N. K. Sah, R. A. Newman, A. Cisneros, and B. B. Aggarwal
Oleandrin Suppresses Activation of Nuclear Transcription Factor-{{kappa}}B, Activator Protein-1, and c-Jun NH2-Terminal Kinase
Cancer Res., July 1, 2000; 60(14): 3838 - 3847.
[Abstract] [Full Text]


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J. Immunol.Home page
S. K. Manna, A. Mukhopadhyay, and B. B. Aggarwal
Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-{kappa}B, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation
J. Immunol., June 15, 2000; 164(12): 6509 - 6519.
[Abstract] [Full Text] [PDF]




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