ArticleAlcoholism, clinical and experimental research2013
Programmed cell death 4 (PDCD4): a novel player in ethanol-mediated suppression of protein translation in primary cortical neurons and developing cerebral cortex.
Article in Alcoholism, clinical and experimental research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Meta-Analysis of Gene Expression Patterns in Animal Models of Prenatal Alcohol Exposure Suggests Role for Protein Synthesis Inhibition and Chromatin Remodeling.Alcoholism, clinical and experimental research · 2016Pooled it
- PDCD4: A Double-Edged Sword in Neurological Diseases.Molecular neurobiology · 2026Review
- Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities.Translational psychiatry · 2024Article
- PDCD4 Simultaneously Promotes Microglia Activation via PDCD4-MAPK-NF-κB Positive Loop and Facilitates Neuron Apoptosis During Neuroinflammation.Inflammation · 2022Article
- Neuronal activity regulates the nuclear proteome to promote activity-dependent transcription.The Journal of cell biology · 2021Article
- Programmed cell death 4 as an endogenous suppressor of BDNF translation is involved in stress-induced depression.Molecular psychiatry · 2021Article
- PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses.RNA (New York, N.Y.) · 2020Article
- Ethanol Impairs NRF2/Antioxidant and Growth Signaling in the Intact Placenta In Vivo and in Human Trophoblasts.Biomolecules · 2019Article
- Translating from cancer to the brain: regulation of protein synthesis by eIF4F.Learning & memory (Cold Spring Harbor, N.Y.) · 2019Review
- Role for Cystathionine γ Lyase (CSE) in an Ethanol (E)-Induced Lesion in Fetal Brain GSH Homeostasis.International journal of molecular sciences · 2018Article
- Ethanol (E) Impairs Fetal Brain GSH Homeostasis by Inhibiting Excitatory Amino-Acid Carrier 1 (EAAC1)-Mediated Cysteine Transport.International journal of molecular sciences · 2017Article
- Ethanol induces cytostasis of cortical basal progenitors.Journal of biomedical science · 2016Article
- Article
- Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation.PloS one · 2013Article
- Astrocytes Prevent Ethanol Induced Apoptosis of Nrf2 Depleted Neurons by Maintaining GSH Homeostasis.Open journal of apoptosis · 2012Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundPrenatal exposure to ethanol (EtOH) elicits a range of neuro-developmental abnormalities, microcephaly to behavioral deficits. Impaired protein synthesis has been connected to pathogenesis of EtOH-induced brain damage and abnormal neuron development. However, mechanisms underlying these impairments of protein synthesis are not known. In this study, we illustrate the effects of EtOH on programmed cell death protein 4 (PDCD4), a tumor and translation repressor.
methodsPrimary cortical neurons (PCNs) were treated with 2.5 and 4 mg/ml EtOH for different time points (4 to 24 hours), and PDCD4 expression was detected by Western blotting. Protein synthesis was determined using [(35) S] methionine incorporation assay. Methyl cap pull-down assay was performed to establish the effect of EtOH on association of eukaryotic initiation factor 4A (eIF4A) with capped mRNA. Luciferase assay was performed to determine the in vivo translation. A 2-day acute 5-dose binge model with EtOH (4 g/kg body wt, 25% v/v) was performed in Sprague-Dawley rats at 12-hour intervals and analyzed for PDCD4, eIF4A, and eIF4A-methyl cap association.
resultsEtOH increased PDCD4 expression in a time- and dose-dependent manner in PCNs, which inhibited the association of eIF4A with methyl cap. EtOH and ectopic PDCD4 expression suppressed in vivo translation in PCNs and RNAi targeting of PDCD4 blocked the inhibitory effect of EtOH on protein synthesis. In utero exposure of pregnant rats to EtOH resulted in a significant increase in PDCD4 in fetal cerebral cortex along with the inhibition of methyl cap-associated eIF4A, compared with isocaloric controls. Increased PDCD4 also occurred in pooled fractions of remaining brain regions.
conclusionsOur data, for the first time, illustrate that PDCD4 mediates inhibitory effects of EtOH on protein synthesis in PCNs and developing brain.
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