scholarly journals Genistein Protects against Tumor Necrosis Factor‐alpha‐Induced Apoptosis of Human Vascular Endothelial Cells

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Hongwei Si ◽  
Dongmin Liu
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

scholarly journals Regulation of thrombomodulin by tumor necrosis factor-alpha: comparison of transcriptional and posttranscriptional mechanisms

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 542-550 ◽  
Author(s):  
SR Lentz ◽  
M Tsiang ◽  
JE Sadler
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Posttranscriptional Regulation ◽  
Tumor Necrosis ◽  
Vascular Endothelial Cells ◽  
Necrosis Factor Alpha ◽  
Subsequent Decrease ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract The procoagulant properties of cultured vascular endothelial cells are enhanced in response to inflammatory cytokines such as tumor necrosis factor-alpha (TNF). A major component of this response is a reduction in expression of thrombomodulin, a cell surface cofactor for the activation of protein C. Regulation of thrombomodulin expression by TNF has been reported to occur through multiple mechanisms. To determine the relative roles of transcriptional and posttranscriptional regulation, the effect of TNF on the turnover of thrombomodulin protein and mRNA was examined in human and bovine endothelial cells. Quantitative nuclease S1 protection assays showed a 70% to 90% reduction in thrombomodulin mRNA within 4 hours of the addition of 1.0 nmol/L TNF to the culture medium. The decrease in thrombomodulin mRNA resulted from inhibition of transcription, followed by rapid degradation of thrombomodulin transcripts (t1/2 less than or equal to 3 hours). In pulse-chase incubations, thrombomodulin synthesis decreased parallel with mRNA, but the rate of degradation of radiolabeled thrombomodulin was not significantly altered by TNF. Human thrombomodulin was degraded with a t1/2 of 8.2 +/- 2.4 hours (SD) or 7.5 +/- 1.3 hours (SD) in the absence or presence of TNF, respectively. We conclude that TNF acts primarily to inhibit thrombomodulin transcription. The subsequent decrease in activity results from the inherent instability of thrombomodulin mRNA and protein in these cells, and not from the regulation of thrombomodulin degradation.

scholarly journals Regulation of thrombomodulin by tumor necrosis factor-alpha: comparison of transcriptional and posttranscriptional mechanisms

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 542-550 ◽  
Author(s):  
SR Lentz ◽  
M Tsiang ◽  
JE Sadler
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Posttranscriptional Regulation ◽  
Tumor Necrosis ◽  
Vascular Endothelial Cells ◽  
Necrosis Factor Alpha ◽  
Subsequent Decrease ◽  
Factor Alpha ◽  
Necrosis Factor

The procoagulant properties of cultured vascular endothelial cells are enhanced in response to inflammatory cytokines such as tumor necrosis factor-alpha (TNF). A major component of this response is a reduction in expression of thrombomodulin, a cell surface cofactor for the activation of protein C. Regulation of thrombomodulin expression by TNF has been reported to occur through multiple mechanisms. To determine the relative roles of transcriptional and posttranscriptional regulation, the effect of TNF on the turnover of thrombomodulin protein and mRNA was examined in human and bovine endothelial cells. Quantitative nuclease S1 protection assays showed a 70% to 90% reduction in thrombomodulin mRNA within 4 hours of the addition of 1.0 nmol/L TNF to the culture medium. The decrease in thrombomodulin mRNA resulted from inhibition of transcription, followed by rapid degradation of thrombomodulin transcripts (t1/2 less than or equal to 3 hours). In pulse-chase incubations, thrombomodulin synthesis decreased parallel with mRNA, but the rate of degradation of radiolabeled thrombomodulin was not significantly altered by TNF. Human thrombomodulin was degraded with a t1/2 of 8.2 +/- 2.4 hours (SD) or 7.5 +/- 1.3 hours (SD) in the absence or presence of TNF, respectively. We conclude that TNF acts primarily to inhibit thrombomodulin transcription. The subsequent decrease in activity results from the inherent instability of thrombomodulin mRNA and protein in these cells, and not from the regulation of thrombomodulin degradation.

scholarly journals Critical involvement of transmembrane tumor necrosis factor-alpha in endothelial programmed cell death mediated by ionizing radiation and bacterial endotoxin

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4184-4193 ◽  
Author(s):  
G Eissner ◽  
F Kohlhuber ◽  
M Grell ◽  
M Ueffing ◽  
P Scheurich ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Programmed Cell Death ◽  
Ionizing Radiation ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

In this report, we show that ionizing radiation (IR) at a clinically relevant dose (4 Gy) causes apoptosis in macrovascular and microvascular human endothelial cells. Treatment of irradiated cells with a low dose of bacterial endotoxin (LPS), similar to the levels observed in serum during endotoxemia, enhanced the rate of apoptosis, although LPS alone was unable to induce programmed cell death. The cytokine and endotoxin antagonist interleukin-10 (IL-10) reduced the rate of LPS + IR-induced apoptosis to levels obtained with irradiation alone. Using neutralizing antibodies against tumor necrosis factor- alpha (TNF), we could show crucial involvement of TNF in the LPS- mediated enhancement of IR-induced apoptosis, but not in the IR-induced apoptosis per se. However, further analysis strongly suggested the transmembrane form of TNF (mTNF), but not soluble TNF, to be accountable for the LPS-mediated cytotoxic effects. Studies with anatagonistic receptor specific antibodies clearly showed that TNF receptor type I (TR60) is essential and sufficient to elicit this effect. These findings are of potential clinical importance because they may disclose a relevant mechanism that leads to endothelial damage after radiotherapy or total body irradiation used for conditioning in bone marrow transplantation and that may thus contribute to transplant related complications, especially in association with endotoxemia or related inflammatory states.

scholarly journals Tumor Necrosis Factor Alpha-Induced Apoptosis Requires p73 and c-ABL Activation Downstream of RB Degradation

2004 ◽  
Vol 24 (10) ◽  
pp. 4438-4447 ◽  
Author(s):  
B. Nelson Chau ◽  
Tung-Ti Chen ◽  
Yisong Y. Wan ◽  
James DeGregori ◽  
Jean Y. J. Wang
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Abl Tyrosine Kinase ◽  
Tnf Α ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT The retinoblastoma protein (RB) suppresses cell proliferation and apoptosis. We have previously shown that RB degradation is required for tumor necrosis factor alpha (TNF-α) to induce apoptosis. We show here the identification of two apoptotic effectors, i.e., c-ABL tyrosine kinase and p73, which are activated by TNF-α following RB degradation. In cells expressing a degradation-resistant RB protein (RB-MI), TNF-α does not activate c-ABL. RB-MI also inhibits TNF-α-mediated activation of p73. Genetic deletion and pharmacological inhibition of c-ABL or p73 diminish the apoptotic response to TNF-α in human cell lines and mouse fibroblasts. Thymocytes isolated from RbMI/MI , Abl −/−, or p73 −/− mice are resistant to TNF-α-induced apoptosis compared to their wild-type counterparts. This is in contrast to p53 −/− thymocytes, which exhibit a wild-type level of apoptosis in response to TNF-α. Thus, c-ABL and p73 contribute to apoptosis induced by TNF-α, in addition to their role in promoting DNA damage-associated cell death.

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