ArticleEukaryotic cell2007
Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid.
Article in Eukaryotic cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
- Pharmacological inhibition of ENT1 enhances the impact of specific dietary fats on energy metabolism gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.Pharmacological reports : PR · 2022Article
- Valproic acid restricts mast cell activation by Listeria monocytogenes.Scientific reports · 2022Article
- Moving the Research Forward: The Best of British Biology Using the Tractable Model SystemCells · 2021Review
- Decanoic Acid Stimulates Autophagy inCells · 2021Article
- Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity.Clinical epigenetics · 2021Article
- Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- UsingFrontiers in cell and developmental biology · 2021Review
- Dictyostelium discoideum as a non-mammalian biomedical model.Microbial biotechnology · 2021Review
- Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- ABiochemistry and biophysics reports · 2020Article
- Rare susceptibility variants for bipolar disorder suggest a role for G protein-coupled receptors.Molecular psychiatry · 2018Article
- Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid inDisease models & mechanisms · 2018Article
- Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues inDisease models & mechanisms · 2018Article
- All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research.Frontiers in cellular neuroscience · 2018Review
- An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders.Translational psychiatry · 2017Article
- Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2017Article
- Valproate Attenuates Nitroglycerin-Induced Trigeminovascular Activation by Preserving Mitochondrial Function in a Rat Model of Migraine.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Seizure control by decanoic acid through direct AMPA receptor inhibition.Brain : a journal of neurology · 2016Article
- Valproic acid protects against haemorrhagic shock-induced signalling changes via PPARγ activation in an in vitro model.British journal of pharmacology · 2015Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PH(Crac)-green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP(3)) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP(2) phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis-processes previously shown to be dependent upon PIP(3) production. These results suggest that in Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug.
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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.