ArticleJournal of psychiatry & neuroscience : JPN2007
Haloperidol induces the nuclear translocation of phosphatidylinositol 3'-kinase to disrupt Akt phosphorylation in PC12 cells.
Article in Journal of psychiatry & neuroscience : JPN, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- New insights into the physiological, pathological and pharmacological roles of voltage‑gated potassium channel Kv10.1 in cancer (Review).International journal of oncology · 2026Review
- Chronic haloperidol exposure impairs neurodevelopment via Notch1 signaling in human stem cell-derived brain organoids.Scientific reports · 2025Article
- Molecular and Behavioral Neuroprotective Effects of Clavulanic Acid and Crocin in Haloperidol-Induced Tardive Dyskinesia in Rats.Molecular neurobiology · 2025Article
- An (Immuno) Fluorescence Protocol for Monitoring Monoamine Oxidase A/B Protein Distribution Within the Cell.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The PI3K regulatory subunits p55α and p50α regulate cell death in vivo.Cell death and differentiation · 2014Article
- Neurodevelopment in schizophrenia: the role of the wnt pathways.Current neuropharmacology · 2013Article
- Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress.The Journal of biological chemistry · 2013Article
- The wnt pathway in mood disorders.Current neuropharmacology · 2012Article
- The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation.Nature medicine · 2010Article
- Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action.The American journal of psychiatry · 2010Review
- Inhibition of the PI3K pathway suppresses hormonal secretion and limits growth in pheochromocytoma cells.World journal of surgery · 2009Article
- Molecular mechanisms and clinical implications of reversible protein S-glutathionylation.Antioxidants & redox signaling · 2008Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe antipsychotic drug haloperidol (HAL) has been linked to apoptosis and to inhibition of prosurvival Akt signalling in pheochromocytoma (PC12) and neuronal cell cultures. However, the mechanism involved is unclear.
methodsWe used HAL to induce cytotoxicity in preneuronal PC12 cells. The expression and the subcellular localization of selected components of the PI3K-Akt survival cascade were monitored with standard biochemical approaches, such as subcellular fractionation, western blot analysis, gene transfer and fluorescence microscopy.
resultsPC12 cell stimulation with the epidermal growth factor (used as a control) results in normal processing of phosphatidylinositol 3'-kinase (PI3K)-Akt signalling (e.g., localization of PI3K to the plasma membrane and phosphorylation of Akt (Ser473). Surprisingly, HAL induces PI3K-generated phosphoinositol [phosphatidylinositol-3,4,5-triphosphate (PIP3), which conflicts with its ability to inhibit Akt. In fact, the production of PIP3s is nuclear, as assessed by the localized concentration of a fluorophore-tagged PIP3-targeting pleckstrin homology protein and a fluorophore-tagged substrate-trapping mutant of the phosphoinositide phosphatase, phosphatase and tensin homologue deleted on chromosome 10 (PTEN). However, phosphoinositide-dependent protein kinase 1 (PDK1, the activating kinase of Akt) does not colocalize to the nucleus with the PI3K complex. This effectively inactivates both cytoplasmic and nuclear pools of Akt.
conclusionThe differential compartmentalization of effectors of the PI3K-PDK1-Akt pathway is a unique means by which HAL disrupts Akt functioning in PC12 cells.
Indexed as
Identifiers
17823648PMC1963350W2249292417What 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.