Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/104423
Title: Curcumin mitigates the intracellular lipid deposit induced by antipsichotics in vitro
Author: Canfrán Duque, Alberto.
Pastor, Oscar
Reina del Pozo, Manuel
Lerma, Milagros.
Cruz Jentoft,Alfonso J.
Lasunción, Miguel A.
Busto, Rebeca
Keywords: Lisosomes
Antipsicòtics
Colesterol
Homeòstasi
Lysosomes
Antipsychotic drugs
Cholesterol
Homeostasis
Issue Date: 30-Oct-2015
Publisher: Public Library of Science (PLoS)
Abstract: Scope First- and second-generation antipsychotics (FGAs and SGAs, respectively), both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychoticinduced intracellular lipid accumulation. Methods HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation. Results Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics. Conclusion Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids) accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0141829
It is part of: PLoS One, 2015, vol. 10, num. 10, p. e0141829
Related resource: https://doi.org/10.1371/journal.pone.0141829
URI: http://hdl.handle.net/2445/104423
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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