scholarly journals PUMA is directly activated by NF-κB and contributes to TNF-α-induced apoptosis

2009 ◽  
Vol 16 (9) ◽  
pp. 1192-1202 ◽  
Author(s):  
P Wang ◽  
W Qiu ◽  
C Dudgeon ◽  
H Liu ◽  
C Huang ◽  
...  
Keyword(s):  
Tnf Α ◽  
Induced Apoptosis

scholarly journals Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced by Vibrio cholerae

Toxins ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 12
Author(s):  
Kohei Ogura ◽  
Kinnosuke Yahiro ◽  
Joel Moss
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Vibrio Cholerae ◽  
Elongation Factor ◽  
Host Cells ◽  
Mitogen Activated Protein Kinase ◽  
Pseudomonas Exotoxin A ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Adp Ribosyltransferase

Pathogenic microorganisms produce various virulence factors, e.g., enzymes, cytotoxins, effectors, which trigger development of pathologies in infectious diseases. Cholera toxin (CT) produced by O1 and O139 serotypes of Vibrio cholerae (V. cholerae) is a major cytotoxin causing severe diarrhea. Cholix cytotoxin (Cholix) was identified as a novel eukaryotic elongation factor 2 (eEF2) adenosine-diphosphate (ADP)-ribosyltransferase produced mainly in non-O1/non-O139 V. cholerae. The function and role of Cholix in infectious disease caused by V. cholerae remain unknown. The crystal structure of Cholix is similar to Pseudomonas exotoxin A (PEA) which is composed of an N-terminal receptor-recognition domain and a C-terminal ADP-ribosyltransferase domain. The endocytosed Cholix catalyzes ADP-ribosylation of eEF2 in host cells and inhibits protein synthesis, resulting in cell death. In a mouse model, Cholix caused lethality with severe liver damage. In this review, we describe the mechanism underlying Cholix-induced cytotoxicity. Cholix-induced apoptosis was regulated by mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways, which dramatically enhanced tumor necrosis factor-α (TNF-α) production in human liver, as well as the amount of epithelial-like HepG2 cancer cells. In contrast, Cholix induced apoptosis in hepatocytes through a mitochondrial-dependent pathway, which was not stimulated by TNF-α. These findings suggest that sensitivity to Cholix depends on the target cell. A substantial amount of information on PEA is provided in order to compare/contrast this well-characterized mono-ADP-ribosyltransferase (mART) with Cholix.

NF-κB Activation Is Related to the Resistance of Lung Cancer Cells to TNF-α-Induced Apoptosis

2000 ◽  
Vol 273 (1) ◽  
pp. 140-146 ◽  
Author(s):  
Jae-Yeol Kim ◽  
Seunghee Lee ◽  
Bin Hwangbo ◽  
Choon-Taek Lee ◽  
Young Whan Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Tnf Α ◽  
Induced Apoptosis

scholarly journals Transcription Factor AP-2α Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer Cells

2001 ◽  
Vol 21 (15) ◽  
pp. 4856-4867 ◽  
Author(s):  
Okot Nyormoi ◽  
Zhi Wang ◽  
Dao Doan ◽  
Maribelis Ruiz ◽  
David McConkey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Caspase 6 ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT Several reports have linked activating protein 2α (AP-2α) to apoptosis, leading us to hypothesize that AP-2α is a substrate for caspases. We tested this hypothesis by examining the effects of tumor necrosis factor alpha (TNF-α) on the expression of AP-2 in breast cancer cells. Here, we provide evidence that TNF-α downregulates AP-2α and AP-2γ expression posttranscriptionally during TNF-α-induced apoptosis. Both a general caspase antagonist (zVADfmk) and a caspase 6-preferred antagonist (zVEIDfmk) inhibited TNF-α-induced apoptosis and AP-2α downregulation. In vivo tests showed that AP-2α was cleaved by caspases ahead of the DNA fragmentation phase of apoptosis. Recombinant caspase 6 cleaved AP-2α preferentially, although caspases 1 and 3 also cleaved it, albeit at 50-fold or higher concentrations. Activated caspase 6 was detected in TNF-α-treated cells, thus confirming its involvement in AP-2α cleavage. All three caspases cleaved AP-2α at asp19 of the sequence asp-arg-his-asp (DRHD19). Mutating D19 to A19abrogated AP-2α cleavage by all three caspases. TNF-α-induced cleavage of AP-2α in vivo led to AP-2α degradation and loss of DNA-binding activity, both of which were prevented by pretreatment with zVEIDfmk. AP-2α degradation but not cleavage was inhibited in vivo by PS-431 (a proteasome antagonist), suggesting that AP-2α is degraded subsequent to cleavage by caspase 6 or caspase 6-like enzymes. Cells transfected with green fluorescent protein-tagged mutant AP-2α are resistant to TNF-α-induced apoptosis, further demonstrating the link between caspase-mediated cleavage of AP-2α and apoptosis. This is the first report to demonstrate that degradation of AP-2α is a critical event in TNF-α-induced apoptosis. Since the DRHD sequence in vertebrate AP-2 is widely conserved, its cleavage by caspases may represent an important mechanism for regulating cell survival, proliferation, differentiation, and apoptosis.

Prevention of TNF-α-induced apoptosis in polyamine-depleted IEC-6 cells is mediated through the activation of ERK1/2

2004 ◽  
Vol 286 (3) ◽  
pp. G479-G490 ◽  
Author(s):  
Sujoy Bhattacharya ◽  
Ramesh M. Ray ◽  
Leonard R. Johnson
Keyword(s):  
Epithelial Cells ◽  
Cytochrome C ◽  
Critical Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Cytochrome C Release ◽  
Erk Phosphorylation ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Jnk Activation

It has been documented that polyamines play a critical role in the regulation of apoptosis in intestinal epithelial cells. We have recently reported that protection from TNF-α/cycloheximide (CHX)-induced apoptosis in epithelial cells depleted of polyamines is mediated through the inactivation of a proapoptotic mediator, JNK. In this study, we addressed the involvement of the MAPK pathway in the regulation of apoptosis after polyamine depletion of IEC-6 cells. Polyamine depletion by α-difluromethylornithine (DFMO) resulted in the sustained activation of ERK in response to TNF-α/CHX treatment. Pretreatment of polyamine-depleted IEC-6 cells with a cell membrane-permeable MEK1/2 inhibitor, U-0126, significantly inhibited TNF-α/CHX-induced ERK phosphorylation and significantly increased DNA fragmentation, JNK activity, and caspase-3 activity in response to TNF-α/CHX. Moreover, the dose dependency of U-0126-mediated inhibition of TNF-α/ CHX-induced ERK phosphorylation correlated with the reversal of the antiapoptotic effect of DFMO. IEC-6 cells expressing constitutively active MEK1 had decreased TNF-α/CHX-induced JNK phosphorylation and were significantly protected from apoptosis. Conversely, a dominant-negative MEK1 resulted in high basal activation of JNK, cytochrome c release, and spontaneous apoptosis. Polyamine depletion of the dominant-negative MEK1 cells did not prevent JNK activation or cytochrome c release and failed to confer protection from both TNF-α/CHX and camptothecin-induced apoptosis. Finally, expression of a dominant-negative mutant of JNK significantly protected IEC-6 cells from TNF-α/CHX-induced apoptosis. These data indicate that polyamine depletion results in the activation of ERK, which inhibits JNK activation and protects cells from apoptosis.

scholarly journals CXCL16 suppresses liver metastasis of colorectal cancer by promoting TNF-α-induced apoptosis by tumor-associated macrophages

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Ji-Ye Kee ◽  
Aya Ito ◽  
Shozo Hojo ◽  
Isaya Hashimoto ◽  
Yoshiko Igarashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Tumor Associated Macrophages ◽  
Tnf Α ◽  
Induced Apoptosis

scholarly journals P-165 Cytometry-Based Single Cell Analysis of Intact Epithelial Signaling Reveals MAPK Activation Divergent from TNF-α-Induced Apoptosis in Vivo

2016 ◽  
Vol 22 ◽  
pp. S59-S60
Author(s):  
Alan Simmons ◽  
Amrita Banerjee ◽  
Eliot McKinley ◽  
Cherieʼ Scurrah ◽  
Jeffrey Franklin ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Mapk Activation ◽  
Tnf Α ◽  
Induced Apoptosis

scholarly journals The protective mechanism of Ginkgolides and Ginkgo flavonoids on the TNF-α induced apoptosis of rat hippocampal neurons and its mechanisms in vitro

Heliyon ◽  
2015 ◽  
Vol 1 (1) ◽  
pp. e00020 ◽  
Author(s):  
Maojuan Guo ◽  
Yanrong Suo ◽  
Qing Gao ◽  
Huan Du ◽  
Wenyun Zeng ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Protective Mechanism ◽  
Tnf Α ◽  
Induced Apoptosis

Local production of TGF β1 inhibits cerebral edema, enhances TNF-α induced apoptosis and improves survival in a murine glioma model

1998 ◽  
Vol 86 (1) ◽  
pp. 46-52 ◽  
Author(s):  
David M Ashley ◽  
John H Sampson ◽  
Gary E Archer ◽  
Laura P Hale ◽  
Darell D Bigner
Keyword(s):  
Cerebral Edema ◽  
Local Production ◽  
Tnf Α ◽  
Glioma Model ◽  
Induced Apoptosis ◽  
Tgf Β1 ◽  
Murine Glioma

scholarly journals Mesothelin confers pancreatic cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and IL-6/Mcl-1 overexpression

2011 ◽  
Vol 10 (1) ◽  
pp. 106 ◽  
Author(s):  
Uddalak Bharadwaj ◽  
Christian Marin-Muller ◽  
Min Li ◽  
Changyi Chen ◽  
Qizhi Yao
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cell Resistance ◽  
Tnf Α ◽  
Induced Apoptosis

Interferon-γ rescues TNF-α-induced apoptosis mediated by up-regulation of TNFR2 on EoL-1 cells

1999 ◽  
Vol 27 (3) ◽  
pp. 512-519 ◽  
Author(s):  
Takeo Horie ◽  
Kunio Dobashi ◽  
Kunihiko Iizuka ◽  
Akihiro Yoshii ◽  
Yasuo Shimizu ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Tnf Α ◽  
Induced Apoptosis
Sign in / Sign up

Export Citation Format

Share Document