ArticleCell death & disease2019
Alcohol exposure alters pre-mRNA splicing of antiapoptotic Mcl-1L isoform and induces apoptosis in neural progenitors and immature neurons.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Ethanol selectively disrupts neuronal microexon regulation and chromatin marks in PC12 cells.Frontiers in cellular neuroscience · 2026Article
- Morphine-inducedFrontiers in neuroscience · 2026Article
- Role of the Transcription Factor CREB in Ethanol-Induced Endoplasmic Reticulum Stress and Apoptosis in PC12 Cells.Biology · 2025Article
- Alternative splicing in addiction.Current opinion in genetics & development · 2025Review
- Glucocorticoids regulate the expression of Srsf1 through Hdac4/Foxc1 axis to induce apoptosis of osteoblasts.Communications biology · 2025Article
- Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences.Oncogene · 2025Article
- Tipping the balance of cell death: alternative splicing as a source of MCL-1S in cancer.Cell death & disease · 2024Review
- Modeling HIV-1 infection and NeuroHIV in hiPSCs-derived cerebral organoid cultures.Journal of neurovirology · 2024Article
- It is not just about transcription: involvement of brain RNA splicing in substance use disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- RNA alternative splicing impacts the risk for alcohol use disorder.Molecular psychiatry · 2023Article
- Serine and arginine rich splicing factor 1: a potential target for neuroprotection and other diseases.Neural regeneration research · 2023Review
- Genome- and transcriptome-wide splicing associations with alcohol use disorder.Scientific reports · 2023Article
- Article
- Modulation of OPRM1 Alternative Splicing by Morphine and HIV-1 Nef.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids.Frontiers in molecular biosciences · 2021Review
- Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies.Annals of the New York Academy of Sciences · 2020Article
- Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids.Translational psychiatry · 2020Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Alternative splicing and expression of splice variants of genes in the brain may lead to the modulation of protein functions, which may ultimately influence behaviors associated with alcohol dependence and neurotoxicity. We recently showed that ethanol exposure can lead to pre-mRNA missplicing of Mcl-1, a pro-survival member of the Bcl-2 family, by downregulating the expression levels of serine/arginine rich splicing factor 1 (SRSF1). Little is known about the physiological expression of these isoforms in neuronal cells and their role in toxicity induced by alcohol exposure during the developmental period. In order to investigate the impact of alcohol exposure on alternative splicing of Mcl-1 pre-mRNA and its role in neurotoxicity, we developed a unique primary human neuronal culture model where neurospheres (hNSPs), neural progenitors (hNPCs), immature neurons, and mature neurons were cultured from the matching donor fetal brain tissues. Our data suggest that neural progenitors and immature neurons are highly sensitive to the toxic effects of ethanol, while mature neuron cultures showed resistance to ethanol exposure. Further analysis of Mcl-1 pre-mRNA alternative splicing by semi-quantitative and quantitative analysis revealed that ethanol exposure causes a significant decrease in Mcl-1L/Mcl-1S ratio in a dose and time dependent manner in neural progenitors. Interestingly, ectopic expression of Mcl-1L isoform in neural progenitors was able to recover the viability loss and apoptosis induced by alcohol exposure. Altogether, these observations suggest that alternative splicing of Mcl-1 may play a crucial role in neurotoxicity associated with alcohol exposure in the developing fetal brain.
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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.