scholarly journals Resistance to Tumor Necrosis Factor-α (TNF-α)-induced Apoptosis in Rat Hepatoma Cells Expressing TNF-α Is Linked to Low Antioxidant Enzyme Expression

2003 ◽  
Vol 278 (32) ◽  
pp. 29626-29632 ◽  
Author(s):  
Yvonni Chovolou ◽  
Wim Watjen ◽  
Andreas Kampkotter ◽  
Regine Kahl
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Enzyme Expression ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells

Tumor necrosis factor-α and ceramide induce cell death through different mechanisms in rat mesangial cells

1999 ◽  
Vol 276 (3) ◽  
pp. F390-F397 ◽  
Author(s):  
Yan-Lin Guo ◽  
Baobin Kang ◽  
Li-Jun Yang ◽  
John R. Williamson
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mesangial Cells ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

It has been proposed that ceramide acts as a cellular messenger to mediate tumor necrosis factor-α (TNF-α)-induced apoptosis. Based on this hypothesis, it was postulated that resistance of some cells to TNF-α cytotoxicity was due to an insufficient production of ceramide on stimulation by TNF-α. The present study was initiated to investigate whether this was the case in mesangial cells, which normally are insensitive to TNF-α-induced apoptosis. Our results indicate that although C2ceramide was toxic to mesangial cells, the cell death it induced differed both morphologically and biochemically from that induced by TNF-α in the presence of cycloheximide (CHX). The most apparent effect of C2ceramide was to cause cells to swell, followed by disruption of the cell membrane. It is evident that C2ceramide caused cell death by necrosis, whereas TNF-α in the presence of CHX killed the cells by apoptosis. C2ceramide did not mimic the effects of TNF-α on the activation of c-Jun NH2-terminal protein kinase and nuclear factor-κB transcription factor. Although mitogen-activated protein kinase [extracellular signal-related kinase (ERK)] was activated by both C2ceramide and TNF-α, such activation appeared to be mediated by different mechanisms as judged from the kinetics of ERK activation. Furthermore, the cleavage of cytosolic phospholipase A2during cell death induced by C2ceramide and by TNF-α in the presence of CHX showed distinctive patterns. The present study provides evidence that apoptosis and necrosis use distinctive signaling machinery to cause cell death.

scholarly journals Contrasting Effects of IG20 and Its Splice Isoforms, MADD and DENN-SV, on Tumor Necrosis Factor α-induced Apoptosis and Activation of Caspase-8 and -3

2001 ◽  
Vol 276 (50) ◽  
pp. 47202-47211 ◽  
Author(s):  
Adeeb M. Al-Zoubi ◽  
Elena V. Efimova ◽  
Shashi Kaithamana ◽  
Osvaldo Martinez ◽  
Mohammed El-Azami El-Idrissi ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Single Gene ◽  
Caspase 8 ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

We identified a novel cDNA (IG20) that is homologous to cDNAs encoding a proteindifferentiallyexpressed innormal andneoplastic cells (DENN-SV) and human MADD (MAPK-activatingdeathdomain-containing protein). Furthermore, we show that the above variants most likely result from alternative splicing of a single gene. Functional analyses of these variants in permanently transfected HeLa cells revealed that IG20 and DENN-SV render them more susceptible or resistant to tumor necrosis factor α (TNF-α)-induced apoptosis, respectively. All variants tested could interact with TNF receptor 1 and activate ERK and nuclear factor κB. However, relative to control cells, only cells expressing IG20 showed enhanced TNF-α-induced activation of caspase-8 and -3, whereas cells expressing DENN-SV showed either reduced or no caspase activation. Transfection of these cells with a cDNA encoding CrmA maximally inhibited apoptosis in HeLa-IG20 cells. Our results show that IG20 can promote TNF-α-induced apoptosis and activation of caspase-8 and -3 and suggest that it may play a novel role in the regulation of the pleiotropic effects of TNF-α through alternative splicing.

scholarly journals Nuclear Factor (NF)-κB–regulated X-chromosome–linked iap Gene Expression Protects Endothelial Cells from Tumor Necrosis Factor α–induced Apoptosis

1998 ◽  
Vol 188 (1) ◽  
pp. 211-216 ◽  
Author(s):  
Christian Stehlik ◽  
Rainer de Martin ◽  
Ichiro Kumabashiri ◽  
Johannes A. Schmid ◽  
Bernd R. Binder ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
X Chromosome ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ectopic Expression ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

By differential screening of tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS)- activated endothelial cells (ECs), we have identified a cDNA clone that turned out to be a member of the inhibitor of apoptosis (iap) gene family. iap genes function to protect cells from undergoing apoptotic death in response to a variety of stimuli. These iap genes, hiap1, hiap2, and xiap were found to be strongly upregulated upon treatment of ECs with the inflammatory cytokines TNF-α, interleukin 1β, and LPS, reagents that lead to activation of the nuclear transcription factor κB (NF-κB). Indeed, overexpression of IκBα, an inhibitor of NF-κB, suppresses the induced expression of iap genes and sensitizes ECs to TNF-α–induced apoptosis. Ectopic expression of one member of the human iap genes, human X-chromosome–linked iap (xiap), using recombinant adenovirus overrules the IκBα effect and protects ECs from TNF-α– induced apoptosis. We conclude that xiap represents one of the NF-κB–regulated genes that counteracts the apoptotic signals caused by TNF-α and thereby prevents ECs from undergoing apoptosis during inflammation.

scholarly journals Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis

2018 ◽  
Vol 49 (6) ◽  
pp. 2427-2442 ◽  
Author(s):  
Siming Li ◽  
Xiaohong Yang ◽  
Zhencheng Feng ◽  
Pengzhen Wang ◽  
Weicong Zhu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Oxygen Species ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Background/Aims: Both physiologic remodeling and pathologic regeneration of cartilage tissue rely upon chondrocyte functions and are benefited from factors that promote viability and inhibit apoptosis of the cell, and associated mechanisms. High level of reactive oxygen species (ROS) and proinflammatory cytokines activate apoptosis signaling and initiate cell death, which can be attenuated by antioxidants. This study examined the effect of catalase (CAT) on ROS and tumor necrosis factor-α (TNF-α)-induced apoptosis in human C28/I2 chondrocytes cultured in monolayer. Methods: Chondrocytes were treated with diluted CAT in the presence or absence of TNF-α and compared to untreated cells. Levels of hydrogen peroxide (H2O2) and mitochondrial membrane potential (Δψm) were measured using fluorescent labeling, cell apoptosis was assayed by flow cytometry using Annexin V/propidium iodide (PI) staining, gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and the proteins were investigated by Western blotting. Results: CAT effectively reduced the intracellular ROS caused by the monolayer culture system, enhanced the Δψm depending on the presence of TNF-α and promoted morphological features at sub-cellular level. CAT also attenuated the TNF-α-upregulated expression of factors/mediators of extrinsic cell death cascade and apoptotic caspases, ultimately resulted in promoted cellular viability. Conclusion: The anti-apoptotic effect of CAT on chondrocytes via scavenging ROS and suppressing TNF-α-induced cell apoptosis by TNF/TNF receptor (TNFR) mediated death signaling pathway and potentiate CAT as a complementary agent beneficial to cartilage remodeling and regeneration in vivo, and cell-based therapies of cartilage repair demanding viable cells expanded ex vivo.

Regulation of Fas (CD95)-induced apoptosis by nuclear factor-κB and tumor necrosis factor-α in macrophages

2002 ◽  
Vol 283 (3) ◽  
pp. C831-C838 ◽  
Author(s):  
Bin Lu ◽  
Liying Wang ◽  
Djordje Medan ◽  
David Toledo ◽  
Chuanshu Huang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

The APO-1/Fas ligand (FasL) and tumor necrosis factor-α (TNF-α) are two functionally related molecules that induce apoptosis of susceptible cells. Although the two molecules have been reported to induce apoptosis via distinct signaling pathways, we have shown that FasL can also upregulate the expression of TNF-α, raising the possibility that TNF-α may be involved in FasL-induced apoptosis. Because TNF-α gene expression is under the control of nuclear factor-κB (NF-κB), we investigated whether FasL can induce NF-κB activation and whether such activation plays a role in FasL-mediated cell death in macrophages. Gene transfection studies using NF-κB-dependent reporter plasmid showed that FasL did activate NF-κB promoter activity. Gel shift studies also revealed that FasL mobilized the p50/p65 heterodimeric form of NF-κB. Inhibition of NF-κB by a specific NF-κB inhibitor, caffeic acid phenylethyl ester, or by dominant expression of the NF-κB inhibitory subunit IκB caused an increase in FasL-induced apoptosis and a reduction in TNF-α expression. However, neutralization of TNF-α by specific anti-TNF-α antibody had no effect on FasL-induced apoptosis. These results indicate that FasL-mediated cell death in macrophages is regulated through NF-κB and is independent of TNF-α activation, suggesting the antiapoptotic role of NF-κB and a separate death signaling pathway mediated by FasL.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

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