Nerve growth factor (NGF) exerts its pro‐apoptotic effect via the P75<sup>NTR</sup> receptor in a cell cycle‐dependent manner

Bono, Françoise; Lamarche, Isabelle; Bornia, Josette; Savi, Pierre; Valle, Giuliano Della; Herbert, Jean‐Marc

doi:10.1016/s0014-5793(99)01006-6

Cited by 24 publications

(13 citation statements)

References 31 publications

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“…The role of NGF is mostly interpreted as a trophic factor that promotes innervation [38]. However, previous studies suggest that NGF could also act as a pro-apoptotic molecule and therefore could induce cell death in the nervous system [39,40]. …”

Section: Discussionmentioning

confidence: 99%

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

Chen¹,

Wang²,

Wang³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Excess maternal salt intake during pregnancy may alter fetal development. However, our knowledge on how an increased salt intake during pregnancy influences fetal eye development is limited. In this study, we investigated the effects of high-salt treatment on the developing eyes in chick embryos, especially focusing on the development of the retina and the lens. Methods: 5.5-day chick embryos were exposed to 280mosm/l (n=17), or 300mosm/l (n=16) NaCl. The treated embryos were then incubated for 96 hours before they were fixed with 4% paraformaldehyde for H&E staining, whole-mount embryo immunostaining and TUNEL staining. BrdU and PH3 incorporation experiments were performed on the chick embryos after high-salt treatment. RT-PCR analyses were conducted from chick retina tissues. Results: We demonstrated that high-salt treatment altered the size of eyes in chick embryos, induced malformation of the eyes and impaired the development of the lens and the retina. We found an impaired expression of Paired box 6 (PAX6) and neuronal cells in the developing retina as revealed by neurofilament immunofluorescent staining. There was a reduction in the number of BrdU-positive cells and PH3-positive cells in the retina, indicating an impaired cell proliferation with high-salt treatment. High-salt treatment also resulted in an increased number of TUNEL-positive cells in the retina, indicating a higher amount of cell death. RT-PCR data displayed that the expression of the pro-apoptotic molecule nerve growth factor (NGF) in chick retina was increased and CyclinD1 was reduced with high-salt treatment. The size of the lens was reduced and Pax6 expression in the lens was significantly inhibited. High salt-treatment was detrimental to the migration of neural crest cells. Conclusion: Taken together, our study demonstrated that high-salt exposure of 5.5-day chick embryos led to an impairment of retina and lens development, possibly through interfering with Pax6 expression.

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Section: Discussionmentioning

confidence: 99%

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

Chen¹,

Wang²,

Wang³

et al. 2014

Cell Physiol Biochem

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“…Enforced expression of Schlafen 2 in transgenic mice has been reported to block double positive thymocyte maturation and to retard fibroblast cell growth in vitro (96). Nerve growth factor has been reported to illicit proapoptotic effects on neuroblastoma cells via the p75 neurotrophin receptor, whereas it can also promote a survival response upon signaling via the homologous TrkA neurotrophin receptor (97). The p75NTR has also been shown to promote apoptosis by binding to ␤ amyloid peptide, an effect that is enhanced by IL-1 signaling (98).…”

Section: Figmentioning

confidence: 99%

IKKα, IKKβ, and NEMO/IKKγ Are Each Required for the NF-κB-mediated Inflammatory Response Program

Li¹,

Massa²,

Hanidu³

et al. 2002

Journal of Biological Chemistry

210

177

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The IKK␤ and NEMO/IKK␥ subunits of the NF-B-activating signalsome complex are known to be essential for activating NF-B by inflammatory and other stresslike stimuli. However, the IKK␣ subunit is believed to be dispensable for the latter responses and instead functions as an in vivo mediator of other novel NF-B-dependent and -independent functions. In contrast to this generally accepted view of IKK␣'s physiological functions, we demonstrate in mouse embryonic fibroblasts (MEFs) that, akin to IKK␤ and NEMO/IKK␥, IKK␣ is also a global regulator of tumor necrosis factor ␣-and IL-1-responsive IKK signalsome-dependent target genes including many known NF-B targets such as serum amyloid A3, C3, interleukin (IL)-6, IL-11, IL-1 receptor antagonist, vascular endothelial growth factor, Ptx3, ␤ 2 -microglobulin, IL-1␣, Mcp-1 and -3, RANTES (regulated on activation normal T cell expressed and secreted), Fas antigen, Jun-B, c-Fos, macrophage colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Only a small number of NF-B-dependent target genes were preferentially dependent on IKK␣ or IKK␤. Constitutive expression of a trans-dominant I B␣ superrepressor (I B␣SR) in wild type MEFs confirmed that these signalsome-dependent target genes were also dependent on NF-B. A subset of NF-B target genes were IKK-dependent in the absence of exogenous stimuli, suggesting that the signalsome was also required to regulate basal levels of activated NF-B in established MEFs. Overall, a sizable number of novel NF-B/IKK-dependent genes were identified including Secreted Frizzled, cadherin 13, protocadherin 7, CCAAT/enhancer-binding protein-␤ and -␦, osteoprotegerin, FOXC2 and FOXF2, BMP-2, p75 neurotrophin receptor, caspase-11, guanylate-binding proteins 1 and 2, ApoJ/clusterin, interferon (␣ and ␤) receptor 2, decorin, osteoglycin, epiregulin, proliferins 2 and 3, stromal cell-derived factor, and cathepsins B, F, and Z. SOCS-3, a negative effector of STAT3 signaling, was found to be an NF-B/IKK-induced gene, suggesting that IKKmediated NF-B activation can coordinately illicit negative effects on STAT signaling.The NF-B transcription factors are pivotal regulators of gene expression programs culminating in stress-like responses and the genesis of innate and acquired immunity (reviewed in Refs. 1-4). A host of extracellular stimuli including inflammatory cytokines, viral and bacterial infections, oxidative and DNA-damaging agents, UV light, and osmotic shock can all result in NF-B activation (1, 3-5). NF-B transcription factors bind to DNA as hetero-or homodimers that are selectively derived from five possible subunits (RelA/p65, c-Rel, RelB, p50, and p52) with each binding to half of a conserved 10-base pair consensus sequence (GGGRNWTYCC) (1, 5). Whereas the RelA/p65 and p50 subunits are ubiquitously expressed, the p52, c-Rel, and RelB subunits are more functionally important in specific differentiated cell types (1, 6). Cytoplasmic p50/p65 heterodimers, c-Rel homodimers, and RelB are bound to I Bs (inhibitors of NF-B...

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“…Effect of NGF-Induced PKC Stimulation on p75 NTR Signaling in SH-SY5Y Cells SH-SY5Y neuroblastoma cells express various levels of TrkA and p75 NTR , depending on culture conditions (Bono et al, 1999). Thus, SH-SY5Y cells represent a useful model for investigating interrelations between TrkA and p75 NTR signaling pathways.…”

Section: Trka Blocks P75mentioning

confidence: 99%

Nerve growth factor‐induced protein kinase C stimulation contributes to TrkA‐dependent inhibition of p75 neurotrophin receptor sphingolipid signaling

Plo

Bono

Bezombes

et al. 2004

J of Neuroscience Research

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Previous studies have established that reciprocal interactions between the low-affinity p75 nerve growth factor (NGF) receptor (p75(NTR)) and the high-affinity TrkA NGF receptor can dictate the cellular response to NGF. As the most important interaction, TrkA signaling was found to inhibit p75(NTR)-mediated sphingomyelinase (SMase) stimulation, ceramide production, and apoptosis. However, the mechanism by which TrkA counteracts p75(NTR)-coupled sphingolipid signaling is still unclear. Considering the stimulatory effect of NGF on protein kinase C (PKC) activity, we investigated the role of PKC in TrkA/p75(NTR) signaling interaction. In this study, we found that, in SK-N-BE cells, which selectively express p75(NTR), phorbol ester-induced PKC stimulation resulted in the abrogation of SMase stimulation and ceramide production induced by NGF. Moreover, in SK-N-BE neuroblastoma cells, which selectively express TrkA, NGF stimulated global PKC activity through two independent pathways involving phospholipase Cgamma (PLCgamma) and phosphoinositide-3 kinase (PI3K). In SH-SY5Y, another neuroblastoma cell line, which coexpresses TrkA and p75(NTR), NGF induced PKC stimulation through a TrkA/PI3K signaling pathway, whereas there was no ceramide production. However, in these cells, the inhibition of TrkA, PI3K, and PKC resulted in the restoration of NGF-induced ceramide production. Thus, our study demonstrates for the first time that TrkA interferes with p75(NTR) signaling through a PI3K/PKC-dependent mechanism.

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Nerve growth factor (NGF) exerts its pro‐apoptotic effect via the P75^NTR receptor in a cell cycle‐dependent manner

Cited by 24 publications

References 31 publications

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

IKKα, IKKβ, and NEMO/IKKγ Are Each Required for the NF-κB-mediated Inflammatory Response Program

Nerve growth factor‐induced protein kinase C stimulation contributes to TrkA‐dependent inhibition of p75 neurotrophin receptor sphingolipid signaling

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Nerve growth factor (NGF) exerts its pro‐apoptotic effect via the P75NTR receptor in a cell cycle‐dependent manner

Cited by 24 publications

References 31 publications

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

IKKα, IKKβ, and NEMO/IKKγ Are Each Required for the NF-κB-mediated Inflammatory Response Program

Nerve growth factor‐induced protein kinase C stimulation contributes to TrkA‐dependent inhibition of p75 neurotrophin receptor sphingolipid signaling

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Nerve growth factor (NGF) exerts its pro‐apoptotic effect via the P75^NTR receptor in a cell cycle‐dependent manner