Cited by 49Lipid Membrane Structure and BehaviorCholesterol and Lipid MetabolismCancer, Lipids, and Metabolism

Haloperidol Disrupts Lipid Rafts and Impairs Insulin Signaling in SH-SY5Y Cells

Sánchez-Wandelmer, J., Dávalos, A., de la Peña, G., Cano, S., Giera, M., Canfrán-Duque, A., Bracher, F., Martín-Hidalgo, A. +3 more·2010·Neuroscience

Abstract

Haloperidol exerts its therapeutic effects basically by acting on dopamine receptors. We previously reported that haloperidol inhibits cholesterol biosynthesis in cultured cells. In the present work we investigated its effects on lipid-raft composition and functionality. In both neuroblastoma SH-SY5Y and promyelocytic HL-60 human cell lines, haloperidol inhibited cholesterol biosynthesis resulting in a decrease of the cell cholesterol content and the accumulation of different sterol intermediates (7-dehydrocholesterol, zymostenol and cholesta-8,14-dien-3beta-ol) depending on the dose of the drug. As a consequence, the cholesterol content in lipid rafts was greatly reduced, and several pre-cholesterol sterols, particularly cholesta-8,14-dien-3beta-ol, were incorporated into the cell membrane. This was accompanied by the disruption of lipid rafts, with redistribution of flotillin-1 and Fyn and the impairment of insulin-Akt signaling. Supplementing the medium with free cholesterol abrogated the effects of haloperidol on lipid-raft composition and functionality. LDL (low-density lipoprotein), a physiological vehicle of cholesterol in plasma, was much less effective in preventing the effects of haloperidol, which is attributed to the drug's inhibition of intracellular vesicular trafficking. These effects on cellular cholesterol homeostasis that ultimately result in the alteration of lipid-raft-dependent insulin signaling action may underlie some of the metabolic effects of this widely used antipsychotic.

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Crossref · 10.1016/j.neuroscience.2010.01.051

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Authors
Sánchez-Wandelmer, J., Dávalos, A., de la Peña, G., Cano, S., Giera, M., Canfrán-Duque, A., Bracher, F., Martín-Hidalgo, A., Fernández-Hernando, C., Lasunción, M. A., & Busto, R.
Affiliations
  • Hospital Universitario Ramón y Cajal (ES)
  • Ludwig-Maximilians-Universität München (DE)
  • Universidad de Alcalá (ES)
Venue
Neuroscience
Publisher
Elsevier BV
Published
2010-04
Volume
167
Issue
1
Pages
143-153
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2046583585
Cited by
49
References
54
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 7
FWCI
1.95
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
haloperidol, lipid rafts, insulin signaling, cholesterol biosynthesis, cholesterol homeostasis, flotillin-1, Fyn, Akt signaling, antipsychotic drugs, SH-SY5Y cells, HL-60 cells, sterol intermediates, LDL cholesterol, neuroblastoma
MeSH terms
Cell Line, Cell Membrane, Cholesterol, Dose-Response Relationship, Drug, Haloperidol, Humans, Insulin, Cholesterol, LDL, Membrane Proteins, Receptor, Insulin, Sterols, Signal Transduction, Dopamine Antagonists, Membrane Microdomains, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-fyn

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