ArticlePloS one2014
Ethanol suppresses PGC-1α expression by interfering with the cAMP-CREB pathway in neuronal cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Timeless and Stainless Alcohol: Concentric Waves from Its Oxidative Metabolism and Related Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Role of the Transcription Factor CREB in Ethanol-Induced Endoplasmic Reticulum Stress and Apoptosis in PC12 Cells.Biology · 2025Article
- Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina.Open medicine (Warsaw, Poland) · 2025Article
- Alcohol as a Modifiable Risk Factor for Alzheimer's Disease-Evidence from Experimental Studies.International journal of molecular sciences · 2023Review
- MicroRNAs in the pathophysiology of Alzheimer's disease and Parkinson's disease: an overview.Molecular neurobiology · 2022Review
- HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.Frontiers in aging neuroscience · 2022Article
- Alcohol inhibits alveolar fluid clearance through the epithelial sodium channel via the A2 adenosine receptor in acute lung injury.Molecular medicine reports · 2021Article
- Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2021Article
- cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease.Biomolecules · 2020Review
- Review
- Adenosine decreases oxidative stress and protects HBiomedical reports · 2018Article
- Mitochondrial Biogenesis in Response to Chromium (VI) Toxicity in Human Liver Cells.International journal of molecular sciences · 2017Article
- Dopamine attenuates ethanol-induced neuroapoptosis in the developing rat retina via the cAMP/PKA pathway.Molecular medicine reports · 2017Article
- Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's Disease.Journal of neurochemistry · 2017Article
- Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases.Journal of medicinal chemistry · 2016Review
- Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis.The Journal of pathology · 2016Article
- A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol.Neurotoxicity research · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Alcohol intoxication results in neuronal apoptosis, neurodegeneration and manifest with impaired balance, loss of muscle coordination and behavioral changes. One of the early events of alcohol intoxication is mitochondrial (Mt) dysfunction and disruption of intracellular redox homeostasis. The mechanisms by which alcohol causes Mt dysfunction, disrupts cellular redox homeostasis and triggers neurodegeneration remains to be further investigated. Proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) plays critical roles in regulating Mt biogenesis and respiration, cellular antioxidant defense mechanism, and maintenance of neuronal integrity and function. In this study, we sought to investigate whether alcohol causes Mt dysfunction and triggers neurodegeneration by suppressing PGC-1α expression. We report that ethanol suppresses PGC-1α expression, and impairs mitochondrial function and enhances cellular toxicity in cultured neuronal cell line and also in human fetal brain neural stem cell-derived primary neurons. Moreover, we report that cells over-expressing exogenous PGC-1α or treated with Rolipram, a selective phosphodiesterase-4 inhibitor, ameliorate alcohol-induced cellular toxicity. Further analysis show that ethanol decreases steady-state intracellular cAMP levels, and thus depletes phosphorylation of cAMP-response element binding protein (p-CREB), the key transcription factor that regulates transcription of PGC-1α gene. Accordingly, we found PGC-1α promoter activity and transcription was dramatically repressed in neuronal cells when exposed to ethanol, suggesting that ethanol blunts cAMP→CREB signaling pathway to interfere with the transcription of PGC-1α. Ethanol-mediated decrease in PGC-1α activity results in the disruption of Mt respiration and function and higher cellular toxicity. This study might lead to potential therapeutic intervention to ameliorate alcohol-induced apoptosis and/or neurodegeneration by targeting PGC-1α.
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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.