scholarly journals Tumor Necrosis Factor α Regulates Responses to Nerve Growth Factor, Promoting Neural Cell Survival but Suppressing Differentiation of Neuroblastoma Cells

2008 ◽  
Vol 19 (3) ◽  
pp. 855-864 ◽  
Author(s):  
Yoshinori Takei ◽  
Ronald Laskey

Although nerve growth factor (NGF) promotes survival of neurons, tumor necrosis factor α (TNF-α) contributes to cell death triggered by NGF depletion, through TNF-α receptor (TNFR) 1. In contrast to this effect, TNF-α can promote neural cell survival via TNF-α receptor TNFR2. Although these findings demonstrate pivotal roles of TNF-α and NGF in cell fate decisions, cross-talk between these signaling pathways has not been clarified. We find that NGF can induce TNF-α synthesis through the nuclear factor-κB transcription factor. This provides a new basis for examining the cross-talk between NGF and TNF-α. Inhibition of TNFR2 shows opposite effects on two downstream kinases of NGF, extracellular signal-regulated kinase (Erk) and Akt. It increases Erk activation by NGF, and this increased activation induces differentiation of neuroblastoma cell lines. Reciprocally, inhibition of TNFR2 decreases Akt activation by NGF. Consistent with an essential role of Akt in survival signaling, inhibition of TNF-α signaling decreases NGF-dependent survival of neurons from rat dorsal root ganglia. Thus, NGF and NGF-induced TNF-α cooperate to activate Akt, promoting survival of normal neural cells. However, the NGF-induced TNF-α suppresses Erk activation by NGF, blocking NGF-induced differentiation of neuroblastoma cells. TNFR2 signaling could be a novel target to modulate cell responses to NGF.

2000 ◽  
Vol 275 (21) ◽  
pp. 16360-16365 ◽  
Author(s):  
Riya Takano ◽  
Shin Hisahara ◽  
Kazuhiko Namikawa ◽  
Hiroshi Kiyama ◽  
Hideyuki Okano ◽  
...  

Reproduction ◽  
2011 ◽  
Vol 142 (2) ◽  
pp. 319-331 ◽  
Author(s):  
Cecilia Garcia-Rudaz ◽  
Mauricio Dorfman ◽  
Srinivasa Nagalla ◽  
Konstantin Svechnikov ◽  
Olle Söder ◽  
...  

Excessive nerve growth factor (NGF) production by the ovary, achieved via a transgenic approach, results in arrested antral follicle growth, reduced ovulatory capacity, and a predisposition to cyst formation in response to mildly elevated LH levels. Two salient features in these mutant mice (termed 17NF) are an elevated production of 17α-hydroxyprogesterone (17-OHP4), testosterone, and estradiol (E2) in response to gonadotropins, and an increased frequency of granulosa cell (GC) apoptosis. In this study, we show that the increase in steroidal response is associated with enhanced expression ofCyp17a1,Hsd17b, andCyp19a1, which encode the enzymes catalyzing the synthesis of 17-OHP4, testosterone, and E2respectively. Using a proteomic approach, we identified stathmin (STMN1), as a protein that is overproduced in 17NF ovaries. In its phosphorylated state, STMN1 mediates a cell death signal initiated by tumor necrosis factor α (TNF). STMN1 is expressed in GCs and excessive NGF increases its abundance as well as that of its forms phosphorylated at serine (Ser) 16, 25, and 38. TNF synthesis is also increased in 17NF ovaries, and this change is abolished by blocking neurotrophic tyrosine kinase receptors. Inhibiting TNF actionsin vivoby administering a soluble TNF receptor prevented the increase in total and phosphorylated STMN1 production, as well as GC apoptosis in NGF-overproducing ovaries. These results indicate that an excess of NGF in the ovary promotes steroidogenesis by enhancing the expression of enzyme genes involved in 17-OHP4, testosterone, and E2synthesis, and causes GC apoptosis by activating a TNF/ STMN1-mediated cell death pathway.


2008 ◽  
Vol 62 (4) ◽  
pp. 1337-1344 ◽  
Author(s):  
Etsuro Ito ◽  
Kotaro Oka ◽  
Carlos Collin ◽  
Bernard G. Schreurs ◽  
Manabu Sakakibara ◽  
...  

2019 ◽  
Vol 16 (1) ◽  
pp. 33-37
Author(s):  
Asadallah Keshmiri ◽  
Ali Reza Derakhshan ◽  
Afsoon Fazlinejad ◽  
Reza Farid-Hosseini

Background: Early mortality rate due to acute myocardial infarction (AMI) is approximately 30%, and half of these deaths occur before reaching a hospital. The prevention and early detection play a key role in reducing mortality in AMI. Hepatocyte Growth Factor (HGF), Interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF-α) are most recent prognostic biomarkers for AMI. The present study was aimed to evaluate the level of these cytokines in AMI. Methods: In this case control study, 39 patients with AMI were compared with 30 healthy subjects. Age, sex and other possible confounding factors were matched. AMI diagnosis was confirmed by typical symptoms, electrocardiogram changes and serum concentration of troponin I and creatine kinase-MB. The levels of TNF-α, IL-6 an HGF at baseline and 3 and 7 days later were measured using ELISA method. Results: Levels of IL-6, TNF-α and HGF increased over time after AMI with ST-segment elevation in study group. The baseline IL-6 levels in AMI group were significantly higher than control group (P<0.05). Conclusions: The results of this study suggest that baseline levels of IL-6 as well as serial changes of serum IL-6, TNF-α and HGF concentrations can be used as potential diagnostic biomarkers in AMI.


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