Reactive oxygen species mediate crosstalk between NF-κB and JNK

Nakano, Hiroyasu; Nakajima, Ayako; Sakon-Komazawa, Sachiko; Jh, Piao; Xue, Xindong; Okumura, Ko

doi:10.1038/sj.cdd.4401830

Cited by 331 publications

(247 citation statements)

References 78 publications

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“…Although the activation mechanisms of JNK have been extensively investigated, the biological consequence of JNK activation in cell death is still controversial [29,[40][41][42][43]. While the functions of the JNKs under physiological conditions are diverse and incompletely understood, there is increasing evidence that JNKs are potent effectors of apoptosis in both the brain and the mammalian inner ear following a variety of injuries.…”

Section: Discussionmentioning

confidence: 99%

Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors

Mamedova

Gao

2006

Biochemical Pharmacology

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ADP is the endogenous agonist for both P2Y 1 and P2Y 12 receptors, which are important therapeutic targets. It was previously demonstrated that ADP and a synthetic agonist, 2-methylthioadenosine 5′-diphosphate (2MeSADP), can induce apoptosis by activating the human P2Y 1 receptor heterologously expressed in astrocytoma cells. However, it was not known whether the P2Y 12 receptor behaved similarly. We demonstrated here that, unlike with the G q -coupled P2Y 1 receptor, activation of the G i -coupled P2Y 12 receptor does not induce apoptosis. Furthermore, activation of the P2Y 12 receptor by either ADP or 2MeSADP significantly attenuates the tumor necrosis factor α (TNFα)-induced apoptosis in 1321N1 human astrocytoma cells. This protective effect was blocked by the P2Y 12 receptor antagonist 2-methylthioAMP and by inhibitors of phospholipase C (U73122) and protein kinase C (chelerythrin), but not by the P2Y 1 receptor antagonist MRS2179. Toward a greater mechanistic understanding, we showed that hP2Y 12 receptor activation by 10 nM 2MeSADP, activates Erk1/2, Akt, and JNK by phosphorylation. However, at a lower protective concentration of 100 pM 2MeSADP, activation of the hP2Y 12 receptor involves only phosphorylated Erk1/2, but not Akt or JNK. This activation is hypothesized as the major mechanism for the protective effect induced by P2Y 12 receptor activation. Apyrase did not affect the ability of TNFα to induce apoptosis in hP2Y 12 -1321N1 cells, suggesting that the endogenous nucleotides are not involved. These results may have important implications for understanding the signaling cascades that follow activation of P2Y 1 and P2Y 12 receptors and their opposing effects on cell death pathways.

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Section: Discussionmentioning

confidence: 99%

Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors

Mamedova

Gao

2006

Biochemical Pharmacology

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“…NF-kB has emerged as a decisive factor in this choice, as highlighted in several excellent reviews on the interplay between the JNK and NF-kB signaling pathways (Luo et al, 2005;Nakano et al, 2006;Papa et al, 2006). Binding of TNFa to its receptor TNF-R1 activates the NF-kB, caspase and JNK signaling cascades that compete with one another to determine the fate of the cell (Figure 2; Micheau and Tschopp, 2003;reviewed in Jaattela and Tschopp, 2003).…”

Section: Implication Of Nf-jb In Apoptosis and Necrosismentioning

confidence: 99%

Current insights into the regulation of programmed cell death by NF-κB

et al. 2006

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“…In addition to these, recent studies have shown that NF-kB suppresses TNFa-induced cell death by inhibiting prolonged c-Jun N-terminal kinase (JNK) activation and reactive oxygen species (ROS) accumulation (Sakon et al, 2003;Pham et al, 2004;Ventura et al, 2004;Kamata et al, 2005). Although various signaling intermediates including ferritin heavy chain and manganese-dependent superoxide dismutase to eliminate ROS accumulation have been identified (Pham et al, 2004;Kamata et al, 2005), it remains controversial whether their functions are essential and/or sufficient for eliminating ROS accumulation (Nakano et al, 2006). Moreover, a recent study has shown that activated caspase 3 cleaves the p75 subunit of complex I of the mitochondrial electron transport chain, which would impair the function of complex I, resulting in ROS accumulation (Ricci et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of c-FLIP promotes caspase-dependent JNK activation and reactive oxygen species accumulation in tumor cells

et al. 2007

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Nuclear factor-kappa B (NF-jB) inhibits cell death through suppression of the caspase cascade, the c-Jun N-terminal kinase (JNK) pathway, and reactive oxygen species (ROS) accumulation. To suppress this antiapoptotic function of NF-jB might be a promising strategy to increase susceptibility of tumor cells to stress-induced cell death. We have recently shown that tumor necrosis factor (TNF)a induces caspase-dependent and -independent JNK activation and ROS accumulation in cellular FLICEinhibitory protein (c-Flip) À/À murine embryonic fibroblasts (MEFs). To apply this observation to tumor therapy, we knocked down c-FLIP by RNA interference in various tumor cells. Consistent with the results using c-Flip À/À MEFs, we found that TNFa stimulation induced caspase-dependent prolonged JNK activation and ROS accumulation, followed by apoptotic and necrotic cell death in various tumor cells. Furthermore, TNFa and Fas induced the cleavage of mitogen-activated protein kinase/ ERK kinase kinase (MEKK)1, resulting in generation of a constitutive active form of MEKK1 leading to JNK activation in c-FLIP knockdown cells. Given that ROS accumulation and necrotic cell death enhance inflammation followed by compensatory proliferation of tumor cells, selective suppression of caspase-dependent ROS accumulation will be an alternative strategy to protect cells from ROS-dependent DNA damage and compensatory tumor progression.

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Reactive oxygen species mediate crosstalk between NF-κB and JNK

Cited by 331 publications

References 78 publications

Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors

Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors

Current insights into the regulation of programmed cell death by NF-κB

Downregulation of c-FLIP promotes caspase-dependent JNK activation and reactive oxygen species accumulation in tumor cells

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