Correlation between Sustained c-Jun N-terminal Protein Kinase Activation and Apoptosis Induced by Tumor Necrosis Factor-α in Rat Mesangial Cells

Guo, Yan‐Lin; Baysal, Kemal; Kang, Baobin; Yang, Lijun; Williamson, John

doi:10.1074/jbc.273.7.4027

Cited by 249 publications

(173 citation statements)

References 50 publications

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“…Given our results and evidence that the promoter of g-GCS contains NF-kB and AP-1 binding sites and that TNF induces the expression of g-GCS , it is possible that g-GCS is the critical mediator. Recently, it was reported that TNF-induced apoptosis requires JNK activation, which suggests this is the critical pathway (Guo et al, 1998;Roulston et al, 1998). We, however, show that g-GCS suppresses TNFinduced activation of both JNK and apoptosis.…”

Section: Discussioncontrasting

confidence: 60%

Overexpression of γ-glutamylcysteine synthetase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1

1999

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Tumor necrosis factor (TNF) is a highly pleiotropic cytokine whose activity is at least partially regulated by the redox status of the cell. The cellular redox status is controlled primarily by glutathione, a major cellular antioxidant, whose synthesis is regulated by the ratelimiting enzyme g-glutamylcysteine synthetase (g-GCS).In the present report we investigated the e ect of g-GCS overexpression on the TNF-induced activation of nuclear transcription factors NF-kB and AP-1, stress-activated protein kinase/c-Jun amino-terminal kinase (JNK) and apoptosis. Transfection of cells with g-GCS cDNA blocked TNF-induced NF-kB activation, cytoplasmic IkBa degradation, nuclear translocation of p65, and NF-kB-dependent gene transcription. g-GCS overexpression also completely suppressed NF-kB activation induced by phorbol ester and okadaic acid, whereas that induced by H 2 O 2 , ceramide, and lipopolysaccharide was minimally a ected. g-GCS also abolished the activation of AP-1 induced by TNF and inhibited TNF-induced activation of JNK and mitogen-activated protein kinase kinase. TNF-mediated cytotoxicity and activation of caspase-3 were both abrogated in g-GCS-overexpressing cells. Overall, our results indicate that most of the pleiotropic actions of TNF are regulated by the glutathione-controlled redox status of the cell.

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Section: Discussioncontrasting

confidence: 60%

Overexpression of γ-glutamylcysteine synthetase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1

1999

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“…To ascertain the specificity of GST-p53 for the oligonucleotide probe, competition assays were also performed (lanes 3 and 4). W and M denote unlabeled wild-type and mutant oligonucleotide competitors, respectively because reports have variously stated that vanadate suppresses, 26,27 enhances, [28][29][30] or induces 31 apoptosis. This may be due to differences in the genetic background of the experimental materials, such as the cells' p53 status, and in the apoptotic stimuli used in these studies.…”

Section: Discussionmentioning

confidence: 99%

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53

et al. 2005

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We previously reported that p42/SETb is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETb's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it.

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“…The redox regulation of caspase activation (59,60) suggests that vesnarinone may suppress caspases through its antioxidant activity. Recently, a role for JNK activation in TNF-induced apoptosis was reported (61)(62)(63). Thus, it is possible that vesnarinone inhibits apoptosis by inhibiting JNK activation.…”

Section: Discussionmentioning

confidence: 99%

Vesnarinone Suppresses TNF-Induced Activation of NF-κB, c-Jun Kinase, and Apoptosis

Manna

Aggarwal

2000

The Journal of Immunology

161

180

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Vesnarinone, a synthetic quinolinone derivative used in the treatment of cardiac failure, exhibits immunomodulatory, anti-inflammatory, and cell growth regulatory properties. The mechanisms underlying these properties are not understood, but due to the critical role of nuclear transcription factor NF-κB in these responses, we hypothesized that vesnarinone must modulate NF-κB activation. We investigated the effect of vesnarinone on NF-κB activation induced by inflammatory agents. Vesnarinone blocked TNF-induced activation of NF-κB in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of IκBα, an inhibitor of NF-κB. The effects of vesnarinone were not cell type specific, as it blocked TNF-induced NF-κB activation in a variety of cells. NF-κB-dependent reporter gene transcription activated by TNF was also suppressed by vesnarinone. The TNF-induced NF-κB activation cascade involving TNF receptor 1-TNF receptor associated death domain-TNF receptor associated factor 2 NF-κB-inducing kinase-IKK was interrupted at the TNF receptor associated factor 2 and NF-κB-inducing kinase sites by vesnarinone, thus suppressing NF-κB reporter gene expression. Vesnarinone also blocked NF-κB activation induced by several other inflammatory agents, inhibited the TNF-induced activation of transcription factor AP-1, and suppressed the TNF-induced activation of c-Jun N-terminal kinase and mitogen-activated protein kinase kinase. TNF-induced cytotoxicity, caspase activation, and lipid peroxidation were also abolished by vesnarinone. Overall, our results indicate that vesnarinone inhibits activation of NF-κB and AP-1 and their associated kinases. This may provide a molecular basis for vesnarinone’s ability to suppress inflammation, immunomodulation, and growth regulation.

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Correlation between Sustained c-Jun N-terminal Protein Kinase Activation and Apoptosis Induced by Tumor Necrosis Factor-α in Rat Mesangial Cells

Cited by 249 publications

References 50 publications

Overexpression of γ-glutamylcysteine synthetase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1

Overexpression of γ-glutamylcysteine synthetase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53

Vesnarinone Suppresses TNF-Induced Activation of NF-κB, c-Jun Kinase, and Apoptosis

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