ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1999
Ras regulates sympathetic neuron survival by suppressing the p53-mediated cell death pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02141035 (Acetyl-l-carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome; a Randomized Control Trial.), which is not on this map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Acetyl-l-carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome; a Randomized Control Trial.
Who cites it
48 citing papers in PubMed, 146 citations in OpenAlex.
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- Promotion of Peripheral Nerve Regeneration by Stimulation of the Extracellular Signal-Regulated Kinase (ERK) Pathway.Anatomical record (Hoboken, N.J. : 2007) · 2019Review
- The Role of PI3K/Akt and ERK in Neurodegenerative Disorders.Neurotoxicity research · 2019Review
- Inhibition of the Ras/Raf/extracellular signal-regulated kinase 1/2 signaling pathway by compounds of natural origin for possible treatment of spinal cord injury: AnExperimental and therapeutic medicine · 2018Article
- Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling.Protein & cell · 2016Article
- Inhibition of the Ras/Raf/ERK1/2 Signaling Pathway Restores Cultured Spinal Cord-Injured Neuronal Migration, Adhesion, and Dendritic Spine Development.Neurochemical research · 2016Article
- Programmed cell death during neuronal development: the sympathetic neuron model.Cell death and differentiation · 2014Review
- Proneurotrophins, seizures, and neuronal apoptosis.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2010Review
- Neuroprotection by NGF and BDNF against neurotoxin-exerted apoptotic death in neural stem cells are mediated through Trk receptors, activating PI3-kinase and MAPK pathways.Neurochemical research · 2009Article
- Casein kinase II contributes to the synergistic effects of BMP7 and BDNF on Smad 1/5/8 phosphorylation in septal neurons under hypoglycemic stress.Journal of neurochemistry · 2009Article
- Regulation of neuronal survival by the extracellular signal-regulated protein kinase 5.Cell death and differentiation · 2009Article
- Neurotrophin receptor activation and expression in human postmortem brain: effect of suicide.Biological psychiatry · 2009Article
- Brain-derived neurotrophic factor: role in depression and suicide.Neuropsychiatric disease and treatment · 2009Article
- Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons.Cell death and differentiation · 2008Article
- The ERK 1 and 2 pathway in the nervous system: from basic aspects to possible clinical applications in pain and visceral dysfunction.Current neuropharmacology · 2007Article
- The latency-associated transcript of herpes simplex virus type 1 promotes survival and stimulates axonal regeneration in sympathetic and trigeminal neurons.Journal of neurovirology · 2007Article
- APPL1 associates with TrkA and GIPC1 and is required for nerve growth factor-mediated signal transduction.Molecular and cellular biology · 2006Article
- Neurotrophin-regulated signalling pathways.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2006Review
- Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Actions of neurotrophic factors and their signaling pathways in neuronal survival and axonal regeneration.Molecular neurobiology · 2006Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this report, we examine how the Ras protein regulates neuronal survival, focusing on sympathetic neurons. Adenovirus-expressed constitutively activated Ras (RasV12) enhanced survival and the phosphorylation of Akt (protein kinase B) and MAP kinase (MAPK), two targets of Ras activity. Functional inhibition of endogenous Ras by adenovirus-expressed dominant-inhibitory Ras (N17Ras) decreased nerve growth factor (NGF)-dependent survival and both Akt and MAPK phosphorylation as well. To determine the signaling pathways through which Ras mediates survival, we used Ras effector mutants and pharmacological inhibitors that selectively suppress phosphatidylinositol 3-kinase (PI3-K)/Akt or MAP kinase kinase (MEK)/MAPK pathways. The Ras effector mutant Ras(V12)Y40C, which selectively stimulates PI3-K and Akt, rescued survival in the absence of NGF, and the PI3-K inhibitor LY 294002 inhibited both Ras- and NGF-dependent survival. Ras(V12)T(35)S, which activates MEK/MAPK but not PI3-K/Akt, was less effective at rescuing survival, whereas the MEK inhibitor PD 098059 also partially suppressed Ras-dependent survival. To investigate the mechanisms by which Ras suppresses neuronal death, we examined whether Ras functions by inhibiting the proapoptotic p53 pathway (Jun-N-terminal kinase/p53/BAX) that is necessary for neuronal death after NGF withdrawal and p75NTR activation. We found that RasV12 suppressed c-jun, BAX, and p53 levels, whereas inhibition of NGF-induced Ras-survival activity via N17Ras increased the levels of these proteins. Furthermore, the E1B55K protein, which suppresses p53 activity, blocked N17Ras-induced neuronal death. Together, these results indicate that Ras is, in part, both necessary and sufficient for survival of sympathetic neurons and that this effect is mediated by activation of both the PI3-K- and MEK-signaling cascades, which in turn suppress a proapoptotic p53 pathway.
Indexed as
Identifiers
10559381PMC6782948W1545645579What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.