Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases
Open accessAbstract
TNFalpha is a pleiotropic cytokine that induces either cell proliferation or cell death. Inhibition of NF-kappaB activation increases susceptibility to TNFalpha-induced death, concurrent with sustained JNK activation, an important contributor to the death response. Sustained JNK activation in NF-kappaB-deficient cells was suggested to depend on reactive oxygen species (ROS), but how ROS affect JNK activation was unclear. We now show that TNFalpha-induced ROS, whose accumulation is suppressed by mitochondrial superoxide dismutase, cause oxidation and inhibition of JNK-inactivating phosphatases by converting their catalytic cysteine to sulfenic acid. This results in sustained JNK activation, which is required for cytochrome c release and caspase 3 cleavage, as well as necrotic cell death. Treatment of cells or experimental animals with an antioxidant prevents H(2)O(2) accumulation, JNK phosphatase oxidation, sustained JNK activity, and both forms of cell death. Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Kinases may be inhibited or activated by ROS.
“In general, phosphatases are inhibited by ROS11, whereas kinases may be inhibited or activated12.”
From ROS in cancer therapy: the bright side of the moon (2020) · cites this paper as [12]
mtROS production is actively triggered by a number of different stimuli including recognition of pathogens and PAMPs or endogenous molecules such as TNF.
“In recent years, however, several studies have shown that mtROS production is actively triggered by a number of different stimuli including the recognition of pathogens and pathogen-associated molecular patterns (PAMPs) [30,61] or endogenous molecules such as TNF [48,136].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [48]
This pro-oxidant effect blunts redox-sensitive phosphatases controlling JNK activation, inducing programmed cell death in response to TNF.
“This pro-oxidant effect blunts the activity of redoxsensitive phosphatases controlling JNK activation [213,214], thus inducing programmed cell death in response to TNF [107,213,215].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [214]
There is a threshold range of ROS concentrations beyond which ROS become harmful, although some increases in ROS can stimulate essential pathways.
“Although some increases in ROS can stimulate these essential pathways, there is a threshold range of concentrations beyond which ROS become harmful (83, 206, 349).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [206]
Prolonged JNK activation can be caused by oxidative inactivation of DUSPs that dephosphorylate JNK.
“Prolonged JNK activation can also be caused by oxidative inactivation of DUSPs that dephosphorylate JNK (206).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [206]
ROS act as inhibitors of protein phosphatases PTEN and PTP1B, and activators of Src family kinases and MAPK.
“To this end, ROS act as inhibitors of protein phosphatases such as PTEN and PTP1B, as well as activators of Src family kinases and MAPK (Denu and Tanner, 1998; Kamata et al., 2005; Lee et al., 2002; Yan and Berton, 1996).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Kamata et al., 2005
The inactivation of MAPK-phosphatases leads to activation of various stress-activated JNK and p38K.
“The inactivation of MAPK-phosphatases leads to activation of various stress-activated JNK and p38K [104], [105].”
The key regulator of NF-κB-mediated inhibition of the JNK pathway is the mitochondrial antioxidant protein SOD2.
“Although NF-κB regulates the expression of several anti-apoptotic genes, the key regulator of NF-κB-mediated inhibition of the JNK pathway is the mitochondrial antioxidant protein SOD2 53.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [53]
ROS have been shown to inhibit other classes of phosphatases, including PTEN and MAPK phosphatases.
“Since then, ROS have been shown to inhibit other classes of phosphatases, including phosphatase and tensin homolog (PTEN, lipid phosphatase) and MAPK phosphatases 51–53.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [53]
Cells without intact NF-κB lack SOD2 induction and accumulate ROS at much higher levels than wild-type cells when treated with TNFα, corresponding with increased JNK activation.
“Cells without intact NF-κB lack SOD2 induction and accumulate ROS at much higher levels than their wild-type counterparts when treated with TNFα, corresponding with increased JNK activation 53, 60.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [53]
The mechanism by which SOD2 confers survival to cells treated with TNFα lies in the ability of ROS to inactivate JNK phosphatases.
“The mechanism by which SOD2 confers survival to cells treated with TNFα lies in the ability of ROS to inactivate JNK phosphatases 53.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [53]
SOD2 provides a protective effect by lowering cellular ROS levels and decreasing JNK activation after TNFα treatment.
“SOD2 provides a protective effect by lowering cellular ROS levels and decreasing JNK activation after TNFα treatment 53.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [53]
Enforced expression of SOD2 in the absence of NF-κB can counteract TNFα-induced cell death.
“and enforced expression of SOD2 in the absence of NF-κB can counteract TNFα-induced cell death 53.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [53]
Cites
Yamada, Y., Kirillova, I., Peschon, J. J., & Fausto, N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1441 · Cited by 944 · see citing works
Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling
De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D. U., Jin, R., Jones, J., Cong, R., & Franzoso, G. (2001) · Nature · doi:10.1038/35104560 · Cited by 732 · see citing works
IKKβ Is Required for Prevention of Apoptosis Mediated by Cell-Bound but Not by Circulating TNFα
Maeda, S., Chang, L., Li, Z.-W., Luo, J.-L., Leffert, H., & Karin, M. (2003) · Immunity · doi:10.1016/s1074-7613(03)00301-7 · Cited by 286 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · see citing works
Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897 · see citing works
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373 · see citing works
Nuclear factor-κB in cancer development and progression
Karin, M. (2006) · Nature · doi:10.1038/nature04870 · Cited by 3,519 · see citing works
Self-citationCrosstalk of reactive oxygen species and NF-κB signaling
Morgan, M. J., & Liu, Z.-G. (2011) · Cell Research · doi:10.1038/cr.2010.178 · Cited by 3,505 · see citing works
Reactive oxygen species, cellular redox systems, and apoptosis
Circu, M. L., & Aw, T. Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.022 · Cited by 3,340 · see citing works
Reactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · see citing works
Integrating cell-signalling pathways with NF-κB and IKK function
Perkins, N. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2083 · Cited by 2,350 · see citing works
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322 · see citing works
ROS in cancer therapy: the bright side of the moon
Perillo, B., Di Donato, M., Pezone, A., Di Zazzo, E., Giovannelli, P., Galasso, G., Castoria, G., & Migliaccio, A. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0384-2 · Cited by 2,176 · see citing works
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781 · see citing works
Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652 · see citing works
Protein misfolding in the endoplasmic reticulum as a conduit to human disease
Wang, M., & Kaufman, R. J. (2016) · Nature · doi:10.1038/nature17041 · Cited by 1,630 · see citing works
Hydrogen peroxide sensing and signaling
Veal, E. A., Day, A. M., & Morgan, B. A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.016 · Cited by 1,604 · see citing works
Sena, L. A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D. A., Wang, C.-R., Schumacker, P. T., Licht, J. D., Perlman, H., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.020 · Cited by 1,338 · see citing works
NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma
Luedde, T., & Schwabe, R. F. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.213 · Cited by 1,345 · see citing works
ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence
Cagnol, S., & Chambard, J. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2009.07366.x · Cited by 1,290 · see citing works
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241 · see citing works
Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?
Son, Y., Cheong, Y.-K., Kim, N.-H., Chung, H.-T., Kang, D. G., & Pae, H.-O. (2011) · Journal of Signal Transduction · doi:10.1155/2011/792639 · Cited by 1,219 · see citing works
Lingappan, K. (2018) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2017.11.002 · Cited by 1,051 · see citing works
The JNK signal transduction pathway
Weston, C. R., & Davis, R. J. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.001 · Cited by 1,021 · see citing works
TNF and ROS crosstalk in inflammation
Blaser, H., Dostert, C., Mak, T. W., & Brenner, D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.12.002 · Cited by 1,008 · see citing works
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011 · see citing works
Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration
Liu, L., Zhang, K., Sandoval, H., Yamamoto, S., Jaiswal, M., Sanz, E., Li, Z., Hui, J., Graham, B. H., Quintana, A., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.019 · Cited by 876 · see citing works
Bulua, A. C., Simon, A., Maddipati, R., Pelletier, M., Park, H., Kim, K.-Y., Sack, M. N., Kastner, D. L., & Siegel, R. M. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102049 · Cited by 860 · see citing works
Tebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.021 · Cited by 837 · see citing works
Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival
Junttila, M. R., Li, S., & Westermarck, J. (2008) · The FASEB Journal · doi:10.1096/fj.06-7859rev · Cited by 826 · see citing works
Cruz, C. M., Rinna, A., Forman, H. J., Ventura, A. L. M., Persechini, P. M., & Ojcius, D. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608083200 · Cited by 786 · see citing works
Mitochondrial reactive oxygen species drive proinflammatory cytokine production
Naik, E., & Dixit, V. M. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110367 · Cited by 783 · see citing works
Redox-based regulation of signal transduction: principles, pitfalls, and promises
Janssen-Heininger, Y. M. W., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., & van der Vliet, A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.011 · Cited by 784 · see citing works
Dual-specificity phosphatases: critical regulators with diverse cellular targets
Patterson, K. I., Brummer, T., O'brien, P. M., & Daly, R. J. (2009) · Biochemical Journal · doi:10.1042/bj20082234 · Cited by 744 · see citing works
Mitochondrial dysfunction in Nash: causes, consequences and possible means to prevent it
Begriche, K., Igoudjil, A., Pessayre, D., & Fromenty, B. (2006) · Mitochondrion · doi:10.1016/j.mito.2005.10.004 · Cited by 753 · see citing works
Takeuchi, H., Jin, S., Wang, J., Zhang, G., Kawanokuchi, J., Kuno, R., Sonobe, Y., Mizuno, T., & Suzumura, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600504200 · Cited by 749 · see citing works
Festjens, N., Vanden Berghe, T., & Vandenabeele, P. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.06.014 · Cited by 710 · see citing works
Chang, L., Kamata, H., Solinas, G., Luo, J.-L., Maeda, S., Venuprasad, K., Liu, Y.-C., & Karin, M. (2006) · Cell · doi:10.1016/j.cell.2006.01.021 · Cited by 706 · see citing works
Self-citationTan, H.-Y., Wang, N., Li, S., Hong, M., Wang, X., & Feng, Y. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/2795090 · Cited by 657 · see citing works
Functions of ROS in Macrophages and Antimicrobial Immunity
Herb, M., & Schramm, M. (2021) · Antioxidants · doi:10.3390/antiox10020313 · Cited by 633 · see citing works
Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Kazama, H., Ricci, J.-E., Herndon, J. M., Hoppe, G., Green, D. R., & Ferguson, T. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.013 · Cited by 627 · see citing works
Bauernfeind, F., Bartok, E., Rieger, A., Franchi, L., Núñez, G., & Hornung, V. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100613 · Cited by 617 · see citing works
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Targeting dual-specificity phosphatases: Manipulating MAP kinase signalling and immune responses
Jeffrey, K. L., Camps, M., Rommel, C., & Mackay, C. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2289 · Cited by 533 · see citing works
The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis
Duran, A., Linares, J. F., Galvez, A. S., Wikenheiser, K., Flores, J. M., Diaz-Meco, M. T., & Moscat, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.02.001 · Cited by 541 · see citing works
Both cIAP1 and cIAP2 regulate TNFα-mediated NF-κB activation
Mahoney, D. J., Cheung, H. H., Mrad, R. L., Plenchette, S., Simard, C., Enwere, E., Arora, V., Mak, T. W., Lacasse, E. C., Waring, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711122105 · Cited by 540 · see citing works
Glutathione primes t cell metabolism for inflammation
Mak, T. W., Grusdat, M., Duncan, G. S., Dostert, C., Nonnenmacher, Y., Cox, M., Binsfeld, C., Hao, Z., Brüstle, A., Itsumi, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.019 · Cited by 511 · see citing works
Molecular Mechanisms and Clinical Implications of Reversible Protein <i>S</i> -Glutathionylation
Mieyal, J. J., Gallogly, M. M., Qanungo, S., Sabens, E. A., & Shelton, M. D. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2089 · Cited by 523 · see citing works
Hanawa, N., Shinohara, M., Saberi, B., Gaarde, W. A., Han, D., & Kaplowitz, N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708916200 · Cited by 527 · see citing works
Nox enzymes and new thinking on reactive oxygen: A double-edged sword revisited
Lambeth, J. D., & Neish, A. S. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104651 · Cited by 495 · see citing works
Good cop, bad cop: the different faces of NF-κB
Perkins, N. D., & Gilmore, T. D. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401838 · Cited by 489 · see citing works
Sakurai, T., He, G., Matsuzawa, A., Yu, G.-Y., Maeda, S., Hardiman, G., & Karin, M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.06.016 · Cited by 487 · see citing works
Self-citationCellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess
Wellen, K. E., & Thompson, C. B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.004 · Cited by 486 · see citing works
Kim, B.-J., Ryu, S.-W., & Song, B.-J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510644200 · Cited by 470 · see citing works
C-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity
Gunawan, B. K., Liu, Z., Han, D., Hanawa, N., Gaarde, W. A., & Kaplowitz, N. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.045 · Cited by 471 · see citing works
Inflammatory process in Alzheimer's Disease
Meraz-Ríos, M. A., Toral-Rios, D., Franco-Bocanegra, D., Villeda-Hernández, J., & Campos-Peña, V. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00059 · Cited by 427 · see citing works
Sturrock, A., Cahill, B., Norman, K., Huecksteadt, T. P., Hill, K., Sanders, K., Karwande, S. V., Stringham, J. C., Bull, D. A., Gleich, M., et al. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00269.2005 · Cited by 402 · see citing works
Bubici, C., Papa, S., Dean, K., & Franzoso, G. (2006) · Oncogene · doi:10.1038/sj.onc.1209936 · Cited by 399 · see citing works
Signal Transduction by Mitochondrial Oxidants
Finkel, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.271999 · Cited by 390 · see citing works
Thomas, S. R., Witting, P. K., & Drummond, G. R. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2027 · Cited by 383 · see citing works
Thiol-based redox switches in eukaryotic proteins
Brandes, N., Schmitt, S., & Jakob, U. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2285 · Cited by 373 · see citing works
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347 · see citing works
Self-citationTNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL
Kim, J. J., Lee, S. B., Park, J. K., & Yoo, Y. D. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2010.19 · Cited by 344 · see citing works
CCN1/CYR61: the very model of a modern matricellular protein
Lau, L. F. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0778-3 · Cited by 338 · see citing works
Roles of oxidative stress in polycystic ovary syndrome and cancers
Zuo, T., Zhu, M., & Xu, W. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8589318 · Cited by 319 · see citing works
Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1
Tang, D., Shi, Y., Kang, R., Li, T., Xiao, W., Wang, H., & Xiao, X. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0806540 · Cited by 312 · see citing works
Molecular Mechanisms of Alcoholic Fatty Liver
Purohit, V., Gao, B., & Song, B. (2009) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00827.x · Cited by 312 · see citing works
Redox regulation of protein kinases
Corcoran, A., & Cotter, T. G. (2013) · The FEBS Journal · doi:10.1111/febs.12224 · Cited by 306 · see citing works
Reactive oxygen species and insulin resistance: the good, the bad and the ugly
Tiganis, T. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.11.006 · Cited by 256 · see citing works
Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors
Canli, Ö., Alankuş, Y. B., Grootjans, S., Vegi, N., Hültner, L., Hoppe, P. S., Schroeder, T., Vandenabeele, P., Bornkamm, G. W., & Greten, F. R. (2016) · Blood · doi:10.1182/blood-2015-06-654194 · Cited by 247 · see citing works
Radical medicine: treating ageing to cure disease
Finkel, T. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1763 · Cited by 234 · see citing works
Bell, E. L., Klimova, T. A., Eisenbart, J., Schumacker, P. T., & Chandel, N. S. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02265-06 · Cited by 237 · see citing works
Cannito, S., Novo, E., di Bonzo, L. V., Busletta, C., Colombatto, S., & Parola, M. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2737 · Cited by 239 · see citing works
ABCA1 and ABCG1 Protect Against Oxidative Stress–Induced Macrophage Apoptosis During Efferocytosis
Yvan-Charvet, L., Pagler, T. A., Seimon, T. A., Thorp, E., Welch, C. L., Witztum, J. L., Tabas, I., & Tall, A. R. (2010) · Circulation Research · doi:10.1161/circresaha.110.217281 · Cited by 217 · see citing works
The Iron age of host–microbe interactions
Soares, M. P., & Weiss, G. (2015) · The EMBO Reports · doi:10.15252/embr.201540558 · Cited by 227 · see citing works
Li, Q., & Engelhardt, J. F. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511153200 · Cited by 219 · see citing works
Bordt, E. A., & Polster, B. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.033 · Cited by 202 · see citing works
Win, S., Than, T. A., Han, D., Petrovic, L. M., & Kaplowitz, N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.276089 · Cited by 197 · see citing works
Chambers, J. W., & LoGrasso, P. V. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.223602 · Cited by 194 · see citing works
Lim, Y.-M., Lim, H., Hur, K. Y., Quan, W., Lee, H.-Y., Cheon, H., Ryu, D., Koo, S.-H., Kim, H. L., Kim, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms5934 · Cited by 189 · see citing works
Zou, J., Wang, Y.-X., Dou, F.-F., Lü, H.-Z., Ma, Z.-W., Lu, P.-H., & Xu, X.-M. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2009.12.021 · Cited by 181 · see citing works
Bianchi, G., Martella, R., Ravera, S., Marini, C., Capitanio, S., Orengo, A., Emionite, L., Lavarello, C., Amaro, A., Petretto, A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3688 · Cited by 173 · see citing works
High Levels of SIRT1 Expression as a Protective Mechanism Against Disease-Related Conditions
Elibol, B., & Kilic, U. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00614 · Cited by 171 · see citing works
VDAC1 at the crossroads of cell metabolism, apoptosis and cell stress
Shoshan-Barmatz, V., N. Maldonado, E., & Krelin, Y. (2017) · Cell Stress · doi:10.15698/cst2017.10.104 · Cited by 170 · see citing works
Nadph oxidase-1 plays a crucial role in hyperoxia-induced acute lung injury in mice
Carnesecchi, S., Deffert, C., Pagano, A., Garrido-Urbani, S., Métrailler-Ruchonnet, I., Schäppi, M., Donati, Y., Matthay, M. A., Krause, K.-H., & Barazzone Argiroffo, C. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200902-0296oc · Cited by 160 · see citing works
Zhang, Z., Teruya, K., Eto, H., & Shirahata, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027441 · Cited by 167 · see citing works
Tomasello, F., Messina, A., Lartigue, L., Schembri, L., Medina, C., Reina, S., Thoraval, D., Crouzet, M., Ichas, F., De Pinto, V., et al. (2009) · Cell Research · doi:10.1038/cr.2009.98 · Cited by 161 · see citing works
Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathways
Papa, S., Bubici, C., Zazzeroni, F., & Franzoso, G. (2009) · bchm · doi:10.1515/bc.2009.111 · Cited by 156 · see citing works
Kudo, H., Takahara, T., Yata, Y., Kawai, K., Zhang, W., & Sugiyama, T. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.02.032 · Cited by 152 · see citing works
Red alert: labile heme is an alarmin
Soares, M. P., & Bozza, M. T. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.11.006 · Cited by 148 · see citing works
Coupling Heme and Iron Metabolism <i>via</i> Ferritin H Chain
Gozzelino, R., & Soares, M. P. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5666 · Cited by 151 · see citing works
Wang, L., Azad, N., Kongkaneramit, L., Chen, F., Lu, Y., Jiang, B.-H., & Rojanasakul, Y. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.3072 · Cited by 151 · see citing works
Cytotoxicity of TNFα is regulated by integrin‐mediated matrix signaling
Chen, C., Young, J. L., Monzon, R. I., Chen, N., Todorović, V., & Lau, L. F. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601596 · Cited by 143 · see citing works
Heijink, A. M., Talens, F., Jae, L. T., van Gijn, S. E., Fehrmann, R. S. N., Brummelkamp, T. R., & van Vugt, M. A. T. M. (2019) · Nature Communications · doi:10.1038/s41467-018-07927-y · Cited by 140 · see citing works
Hou, N., Torii, S., Saito, N., Hosaka, M., & Takeuchi, T. (2008) · Endocrinology · doi:10.1210/en.2007-0988 · Cited by 141 · see citing works
Nitroxidative signaling mechanisms in pathological pain
Grace, P. M., Gaudet, A. D., Staikopoulos, V., Maier, S. F., Hutchinson, M. R., Salvemini, D., & Watkins, L. R. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.10.003 · Cited by 128 · see citing works
Song, B.-J., Akbar, M., Abdelmegeed, M. A., Byun, K., Lee, B., Yoon, S. K., & Hardwick, J. P. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.004 · Cited by 123 · see citing works
Wang, L.-W., Tu, Y.-F., Huang, C.-C., & Ho, C.-J. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-175 · Cited by 119 · see citing works
Herb, M., Gluschko, A., Wiegmann, K., Farid, A., Wolf, A., Utermöhlen, O., Krut, O., Krönke, M., & Schramm, M. (2019) · Science Signaling · doi:10.1126/scisignal.aar5926 · Cited by 119 · see citing works
Kiessling, M. K., Klemke, C. D., Kamiński, M. M., Galani, I. E., Krammer, P. H., & Gülow, K. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3221 · Cited by 115 · see citing works
- Authors
- Kamata, H., Honda, S.-I., Maeda, S., Chang, L., Hirata, H., & Karin, M.
- Affiliations
- University of Hyogo (JP)
- University of California San Diego (US)
- Corresponding author
- Karin, Michael
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 120
- Issue
- 5
- Pages
- 649-661
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2114111268
- Cited by
- 1,792
- References
- 3
- Citations by year
- 2026: 30 · 2025: 41 · 2024: 49 · 2023: 56 · 2022: 56 · 2021: 82 · 2020: 74 · 2019: 74 · 2018: 65 · 2017: 94 · 2016: 80 · 2015: 88 · 2014: 98 · 2013: 97 · 2012: 94
- FWCI
- 46.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5P42 ES10337, AI43477, ES04151, ES06376)
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology (16570121)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- reactive oxygen species, TNF-α, JNK activation, MAP kinase phosphatase, cysteine oxidation, sulfenic acid, mitochondrial superoxide dismutase, NF-κB, cytochrome c release, caspase-3, necrosis, antioxidants, acute liver failure, liver regeneration, oxidative stress
- MeSH terms
- Animals, Antioxidants, Chlorocebus aethiops, Enzyme Activation, HeLa Cells, Humans, Hydrogen Peroxide, Necrosis, Oxidation-Reduction, Phosphoric Monoester Hydrolases, Sulfenic Acids, Superoxide Dismutase, Tumor Necrosis Factor-alpha, Cell Death, Liver Failure, Acute, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, COS Cells, Caspases, Cytochromes c, JNK Mitogen-Activated Protein Kinases, Mice, Caspase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
