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

Takei, Yoshiaki; Laskey, Ronald A.

doi:10.1091/mbc.e07-06-0624

Cited by 25 publications

(27 citation statements)

References 30 publications

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“…Although TNFR1 is ubiquitously expressed, TNFR2 expression is more limited (21). Previous research has shown, however, that TNF-␣ can promote cell survival in PC12 cells through TNFR2 (22). In our model, TNF-␣ may be preferentially activating TNFR2, leading to the activation of IKK and subsequent ASK1 inhibition.…”

Section: Discussionmentioning

confidence: 83%

Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade

Puckett

Goldman²,

Cockrell³

et al. 2013

Molecular and Cellular Biology

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g Cellular processes are tightly controlled through well-coordinated signaling networks that respond to conflicting cues, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress signals, and survival factors to ensure proper cell function. We report here a direct interaction between inhibitor of B kinase (IKK) and apoptosis signal-regulating kinase 1 (ASK1), unveiling a critical node at the junction of survival, inflammation, and stress signaling networks. IKK can be activated by growth factor stimulation or tumor necrosis factor alpha engagement. IKK forms a complex with and phosphorylates ASK1 at a sensor site, Ser967, leading to the recruitment of 14-3-3, counteracts stress signal-triggered ASK1 activation, and suppresses ASK1-mediated functions. An inhibitory role of IKK in JNK signaling has been previously reported to depend on NF-B-mediated gene expression. Our data suggest that IKK has a dual role: a transcription-dependent and a transcription-independent action in controlling the ASK1-JNK axis, coupling IKK to ROS and ER stress response. Direct phosphorylation of ASK1 by IKK also defines a novel IKK phosphorylation motif. Because of the intimate involvement of ASK1 in diverse diseases, the IKK/ASK1 interface offers a promising target for therapeutic development.

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Section: Discussionmentioning

confidence: 83%

Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade

Puckett

Goldman²,

Cockrell³

et al. 2013

Molecular and Cellular Biology

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“…For neurite outgrowth, in addition to NGF, evidence points to the participation of the p75 NTR neurotrophin and Akt pathways. Earlier works suggest that NGF, TNF-␣ and their receptors may all be involved in regulating the proliferation and differentiation of B12-lacking cells (26,27). NGF can induce the synthesis of TNF-␣ through NF-B in neurons, and TNF-␣ can induce the expression of NGF in glia.…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACE

Battaglia-Hsu

Akchiche

Noel

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Vitamin B12 (cobalamin, Cbl) is indispensable for proper brain development and functioning, suggesting that it has neurotrophic effects beside its well-known importance in metabolism. The molecular basis of these effects remains hypothetical, one of the reasons being that no efficient cell model has been made available for investigating the consequences of B12 cellular deficiency in neuronal cells. Here, we designed an approach by stable transfection of NIE115 neuroblastoma cells to impose the anchorage of a chimeric B12-binding protein, transcobalamin-oleosin (TO) to the intracellular membrane. This model produced an intracellular sequestration of B12 evidenced by decreased methyl-Cbl and Sadenosylmethionine and increased homocysteine and methylmalonic acid concentrations. B12 deficiency affected the proliferation of NIE115 cells through an overall increase in catalytic protein phosphatase 2A (PP2A), despite its demethylation. It promoted cellular differentiation by improving initial outgrowth of neurites and, at the molecular level, by augmenting the levels of proNGF and p75 NTR . The up-regulation of PP2A and pro-nerve growth factor (NGF) triggered changes in ERK1/2 and Akt, two signaling pathways that influence the balance between proliferation and neurite outgrowth. Compared with control cells, a 2-fold increase of p75 NTR -regulated intramembraneous proteolysis (RIP) was observed in proliferating TO cells (P < 0.0001) that was associated with an increased expression of two tumor necrosis factor (TNF)-␣ converting enzyme (TACE) secretase enzymes, Adam 10 and Adam 17. In conclusion, our data show that B12 cellular deficiency produces a slower proliferation and a speedier differentiation of neuroblastoma cells through interacting signaling pathways that are related with increased expression of PP2A, proNGF, and TACE.homocysteine ͉ neurotrophin V itamin B12 (B12, also named cobalamin, Cbl) deficiency has long been associated with pernicious anaemia (1) and neurological disorders that range from minor behavior changes to severe neurodegenerative disorders (2). Molecular mechanisms are still lacking to explain how the deficiency can bring about all of the symptoms observed. Indeed, only two enzymes are B12-dependent in mammalian cells: the mitochondrial enzyme L-methylmalonyl-CoA mutase (EC 5.4.99.2) and the cytoplasmic homocysteine methyltransferase, also referred as methionine synthase (EC 2.1.1.13). Inferences are thus based on the two direct consequences of B12 deficiency: the accumulation of methylmalonic acid (MMA) and homocysteine (Hcy). Until now, the consequences of B12 deficiency in the brain have been difficult to evidence because of the experimental limitations of the classical cell models. Indeed, the minute amount of vitamin B12 needed by cells can be provided in vitro by B12 from the FCS, which can bind the ''autocrine'' B12 carrier protein, transcobalamin (TC) (3, 4).To delineate the role of B12 in neurological disorders, we designed a neuronal cell model made deficient in B12 through the stable ...

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“…cells, as described below. More recently, NGF has been reported to induce TNF-a expression in neurons [11]. These findings suggest a positive-feedback loop of TNF-a and NGF expression between glial cells and neurons.…”

Section: Introductionmentioning

confidence: 83%

“…Then, in 2003, it was shown that human and rat, but not mouse, adult neural stem cells express TNF-a under standard growth conditions in vitro [17]. Recently, our group reported that undifferentiated SH-SY5Y and BE(2)-C human neuroblastoma cell lines, as well as the human non-transformed cortical neural cell line HCN-1A, exhibit increased TNF-a expression in response to NGF [11]. These reports indicate that neurons can produce TNF-a from early stages of differentiation to terminal stages.…”

Section: Introductionmentioning

confidence: 99%

Interpreting crosstalk between TNF-α and NGF: potential implications for disease

Takei

Laskey

2008

Trends in Molecular Medicine

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

Cited by 25 publications

References 30 publications

Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade

Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade

Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACE

Interpreting crosstalk between TNF-α and NGF: potential implications for disease

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