Differential Protection with Inhibitors of Caspase-8 and Caspase-3 in Murine Models of Tumor Necrosis Factor and Fas Receptor-Mediated Hepatocellular Apoptosis

2001 ◽  
Vol 175 (3) ◽  
pp. 243-252 ◽  
Author(s):  
Mary Lynn Bajt ◽  
Steven L. Vonderfecht ◽  
Hartmut Jaeschke
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Differential Protection ◽  
Murine Models ◽  
Fas Receptor ◽  
Hepatocellular Apoptosis ◽  
Necrosis Factor

scholarly journals LIGHT, a Member of the Tumor Necrosis Factor Ligand Superfamily, Prevents Tumor Necrosis Factor-α-mediated Human Primary Hepatocyte Apoptosis, but Not Fas-mediated Apoptosis

2002 ◽  
Vol 277 (51) ◽  
pp. 50054-50061 ◽  
Author(s):  
Hideki Matsui ◽  
Yukiko Hikichi ◽  
Isamu Tsuji ◽  
Takao Yamada ◽  
Yasushi Shintani
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Caspase 8 ◽  
Death Domain ◽  
Human Primary Hepatocytes ◽  
Induced Apoptosis ◽  
Necrosis Factor

LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its receptors have been identified as lymphotoxin-β receptor (LTβR) and the herpesvirus entry mediator (HVEM)/ATAR/TR2, both of which lack the cytoplasmic sequence termed the “death domain.” The present study has demonstrated that LIGHT inhibits TNFα-mediated apoptosis of human primary hepatocytes sensitized by actinomycin D (ActD), but not Fas- or TRAIL-mediated apoptosis. Furthermore, LIGHT does not prevent some cell lines such as HepG2 or HeLa from undergoing ActD/TNFα-induced apoptosis. This protective effect requires LIGHT pretreatment at least 3 h prior to ActD sensitization. LIGHT stimulates nuclear factor-κB (NF-κB)-dependent transcriptional activity in human hepatocytes like TNFα. The time course of NF-κB activation after LIGHT administration is similar to that of the pretreatment required for the anti-apoptotic effect of LIGHT. LIGHT inhibits caspase-3 processing on the apoptotic protease cascade in TNFα-mediated apoptosis but not Fas-mediated apoptosis. In addition, increased caspase-3 and caspase-8 activities in ActD/TNFα-treated cells are effectively blocked by LIGHT pretreatment. However, LIGHT does not change the expression of TNFRp55, TNFRp75, and Fas. These results indicate that LIGHT may act as an anti-apoptotic agent against TNFα-mediated liver injury by blocking the activation of both caspase-3 and caspase-8.

Caspases Mediate Tumor Necrosis Factor-–Induced Neutrophil Apoptosis and Downregulation of Reactive Oxygen Production

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 674-685 ◽  
Author(s):  
Kouhei Yamashita ◽  
Atsushi Takahashi ◽  
Susumu Kobayashi ◽  
Hirokazu Hirata ◽  
Peter W. Mesner ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Caspase 8 ◽  
Neutrophil Apoptosis ◽  
Oxygen Production ◽  
Caspase Activation ◽  
Necrosis Factor ◽  
Superoxide Release

Tumor necrosis factor- (TNF-) exerts two separate effects on neutrophils, stimulating effector functions while simultaneously inducing apoptosis. We examined here the involvement of caspases in neutrophil apoptosis and the effect of TNF-–induced apoptosis on reactive oxygen production. Immunoblotting and affinity labeling showed activation of caspase-8, caspase-3, and a caspase with a large subunit of 18 kD (T18) in TNF-–treated neutrophils. Active caspase-6 and -7 were not detectable in this cell type. Caspase-8 activated caspase-3 and T18 in neutrophil cytoplasmic extracts. zVAD-fmk blocked neutrophil apoptosis, in parallel with the inhibition of caspase activation. TNF-–induced caspase activation was accompanied by a decrease in the ability of neutrophils to release superoxide anion. Conversely, TNF- treatment in the presence of zVAD-fmk caused a prolonged augmentation of superoxide release. Granulocyte-macrophage colony-stimulating factor inhibited TNF-–induced caspase activation and apoptosis, while reversing the diminution in superoxide release. These observations not only suggest that a caspase cascade mediates apoptotic events and downregulates oxygen radical production in TNF-–treated neutrophils, but also raise the possibility that suppression of caspase activation with enhanced proinflammatory actions of TNF- may underlie the pathogenesis of inflammatory diseases.

Caspases Mediate Tumor Necrosis Factor-–Induced Neutrophil Apoptosis and Downregulation of Reactive Oxygen Production

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 674-685 ◽  
Author(s):  
Kouhei Yamashita ◽  
Atsushi Takahashi ◽  
Susumu Kobayashi ◽  
Hirokazu Hirata ◽  
Peter W. Mesner ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Caspase 8 ◽  
Neutrophil Apoptosis ◽  
Oxygen Production ◽  
Caspase Activation ◽  
Necrosis Factor ◽  
Superoxide Release

Abstract Tumor necrosis factor- (TNF-) exerts two separate effects on neutrophils, stimulating effector functions while simultaneously inducing apoptosis. We examined here the involvement of caspases in neutrophil apoptosis and the effect of TNF-–induced apoptosis on reactive oxygen production. Immunoblotting and affinity labeling showed activation of caspase-8, caspase-3, and a caspase with a large subunit of 18 kD (T18) in TNF-–treated neutrophils. Active caspase-6 and -7 were not detectable in this cell type. Caspase-8 activated caspase-3 and T18 in neutrophil cytoplasmic extracts. zVAD-fmk blocked neutrophil apoptosis, in parallel with the inhibition of caspase activation. TNF-–induced caspase activation was accompanied by a decrease in the ability of neutrophils to release superoxide anion. Conversely, TNF- treatment in the presence of zVAD-fmk caused a prolonged augmentation of superoxide release. Granulocyte-macrophage colony-stimulating factor inhibited TNF-–induced caspase activation and apoptosis, while reversing the diminution in superoxide release. These observations not only suggest that a caspase cascade mediates apoptotic events and downregulates oxygen radical production in TNF-–treated neutrophils, but also raise the possibility that suppression of caspase activation with enhanced proinflammatory actions of TNF- may underlie the pathogenesis of inflammatory diseases.

scholarly journals Antiapoptotic effect of exercise training on ovariectomized rat hearts

2016 ◽  
Vol 121 (2) ◽  
pp. 457-465 ◽  
Author(s):  
Chih-Yang Huang ◽  
Yi-Yuan Lin ◽  
Chih-Chao Hsu ◽  
Shiu-Min Cheng ◽  
Woei-Cherng Shyu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Exercise Training ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Treadmill Running ◽  
Ovariectomized Rats ◽  
Ovariectomized Rat ◽  
Fas Receptor ◽  
Apoptotic Pathways ◽  
Necrosis Factor

The purpose of this study was to evaluate the effects of exercise training on cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats, which were divided into a sham-operated group, a bilaterally ovariectomized group (OVX), and a bilaterally ovariectomized group that underwent treadmill running exercise for 60 min/day, 5 sessions/wk, for 10 wk (OVX-EX). The abnormal myocardial architecture, cardiac trichome-stained fibrosis and cardiac TUNEL-positive apoptotic cells in ovariectomized rats improved after exercise training. The protein levels of tumor necrosis factor-α, tumor necrosis factor receptor 1, Fas ligand, Fas receptors, Fas-associated death domain, activated caspase-8 and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid, Bad, Bak, Bax, cytosolic cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the OVX-EX group compared with the OVX group. Exercise training suppressed ovariectomy-induced cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rat models. These findings might indicate a new therapeutic effect for exercise training to prevent cardiac apoptosis in menopausal or bilaterally oophorectomized women.

Increased sensitivity of T lymphocytes to tumor necrosis factor receptor 1 (TNFR1)– and TNFR2-mediated apoptosis in HIV infection: relation to expression of Bcl-2 and active caspase-8 and caspase-3

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1666-1675 ◽  
Author(s):  
Luzia Maria de Oliveira Pinto ◽  
Sylvie Garcia ◽  
Hervé Lecoeur ◽  
Christophe Rapp ◽  
Marie-Lise Gougeon
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Hiv Infection ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Tumor Necrosis Factor Receptor ◽  
Caspase 8 ◽  
Hiv Patients ◽  
Necrosis Factor

The destruction of CD4 T cells in human immunodeficiency virus (HIV) infection is associated with activation of apoptotic programs, partly mediated by death receptors. The role of CD95L/CD95 in depletion of patients' CD4 T cells is well documented, but the possible contribution of the tumor necrosis factor/tumor necrosis factor receptor (TNF/TNFR) pathway has not been examined. In this study, we found that both TNFR1 and TNFR2 induced marked apoptosis in peripheral T cells from HIV-infected persons, involving both CD4 and CD8 T cells. Longitudinal follow-up of HIV+ patients suggests an association between the in vivo evolution of CD4 T-cell numbers and variations in susceptibility to TNFR-induced apoptosis. Analysis of molecular mechanisms involved showed that it was not related to altered ex vivo expression of TNFR1-associated death domain, receptor interacting protein, or TNFR-associated factor 2. Susceptibility to TNFR-mediated apoptosis was rather related to Bcl-2 expression, because patients' T cells expressing high levels of Bcl-2 were completely protected from TNFR1- and TNFR2-induced cell death, whereas T cells expressing normal levels of Bcl-2 were not protected in patients in contrast to controls. Early recruitment of caspase-8 and caspase-3 is needed to transduce the apoptotic signals, and expression of both caspases in their active form was detected in blood T cells from HIV+ patients, whereas it was hardly detected in controls. Moreover, ligation of TNFRs induced increased activation of both caspases in patients' T cells. Together these data demonstrate that exacerbated TNFR-mediated cell death of T cells from HIV-infected individuals is associated with both alteration of Bcl-2 expression and activation of caspase-8 and caspase-3 and may contribute to the pathogenesis of acquired immunodeficiency syndrome.

scholarly journals Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis

Neoplasia ◽  
2011 ◽  
Vol 13 (10) ◽  
pp. 971-IN29 ◽  
Author(s):  
Bram Laukens ◽  
Claudia Jennewein ◽  
Barbara Schenk ◽  
Nele Vanlangenakker ◽  
Alexander Schier ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Caspase 8 ◽  
Apoptosis Resistance ◽  
Smac Mimetic ◽  
Factor Α ◽  
Necrosis Factor
Sign in / Sign up

Export Citation Format

Share Document