scholarly journals Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death.

1996 ◽  
Vol 98 (12) ◽  
pp. 2854-2865 ◽  
Author(s):  
K A Krown ◽  
M T Page ◽  
C Nguyen ◽  
D Zechner ◽  
V Gutierrez ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Signaling Cascade ◽  
Cardiac Cell ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

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.

Role of lipopolysaccharide and tumor necrosis factor-alpha in induction of hepatocyte necrosis

1995 ◽  
Vol 269 (2) ◽  
pp. G297-G304 ◽  
Author(s):  
J. H. Wang ◽  
H. P. Redmond ◽  
R. W. Watson ◽  
D. Bouchier-Hayes
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Acute Hepatic Failure ◽  
Tnf Alpha ◽  
Enzyme Release ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

The occurrence of acute hepatic failure during systemic inflammatory response syndrome (SIRS) is related to the extent of hepatocyte (HC) damage and cell death resulting from necrosis or apoptosis. We hypothesized that proinflammatory mediators such as lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) can, either directly or indirectly through neutrophil (PMN) and Kupffer cell (KC) activation, induce HC damage and cell death, and that the mechanism is cellular necrosis rather than apoptosis. The results in this study demonstrated that LPS and TNF-alpha alone and in combination are directly cytotoxic to cultured rat HC as indicated by the hepatocellular enzyme release and HC necrosis. However, LPS and TNF-alpha, in the presence of sodium arsenite (a heat shock inducer), were unable to induce HC apoptosis. Both KC and PMN activated by either LPS or TNF-alpha induced significant hepatocellular enzyme release and HC necrosis, which was dependent on the ratio of KC and PMN to HC. It is concluded that LPS and TNF-alpha may play a central role in the development of acute hepatic failure after severe trauma and sepsis by directly or indirectly inducing HC necrosis rather than apoptosis.

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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