Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis

Methadone is a widely used therapeutic opioid in narcotic addiction and neuropathic pain syndromes. Oncologists regularly use methadone as a long-lasting analgesic. Recently it has also been proposed as a promising agent in leukemia therapy, especially when conventional therapies are not effective....

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Autores: Perez-Alvarez, Sergio, Cuenca-Lopez, Maria D., Melero Fernandez de Mera, Raquel Maria, Puerta, Elena, Karachitos, Andonis, Bednarczyk, Piotr, Kmita, Hanna, Aguirre, Norberto, Galindo, Maria F, Jordán, Joaquin
Tipo de documento: artigo
Data de publicação:2010
País:España
Recursos:Universidad Camilo José Cela (UCJC)
Repositório:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1231
Acesso em linha:https://www.scopus.com/record/display.uri?eid=2-s2.0-77956647666&origin=inward&txGid=37fa75acb8aa751c9c0b7a7a8d5643a8
https://pubmed.ncbi.nlm.nih.gov/20691259/
http://hdl.handle.net/20.500.12020/1231
Access Level:Acceso aberto
Palavra-chave:Biología Celular y Molecular
Ciencias Biomédicas
Bax
Clark electrode
Methadone
Mitochondria
Necrosis
Neurodegeneration
32 Ciencias Médicas
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spelling Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesisPerez-Alvarez, SergioCuenca-Lopez, Maria D.Melero Fernandez de Mera, Raquel MariaPuerta, ElenaKarachitos, AndonisBednarczyk, PiotrKmita, HannaAguirre, NorbertoGalindo, Maria FJordán, JoaquinBiología Celular y MolecularCiencias BiomédicasBaxClark electrodeMethadoneMitochondriaNecrosisNeurodegeneration32 Ciencias MédicasMethadone is a widely used therapeutic opioid in narcotic addiction and neuropathic pain syndromes. Oncologists regularly use methadone as a long-lasting analgesic. Recently it has also been proposed as a promising agent in leukemia therapy, especially when conventional therapies are not effective. Nevertheless, numerous reports indicate a negative impact on human cognition with chronic exposure to opiates. Thus, clarification of methadone toxicity is required. In SH-SY5Y cells we found that high concentrations of methadone were required to induce cell death. Methadone-induced cell death seems to be related to necrotic processes rather than typical apoptosis. Cell cultures challenged with methadone presented alterations in mitochondrial outer membrane permeability. A mechanism that involves Bax translocation to the mitochondria was observed, accompanied with cytochrome c release. Furthermore, no participation of known protein regulators of apoptosis such as Bcl-XL and p53 was observed. Interestingly, methadone induced cell death took place by a caspases-independent pathway; perhaps due to its ability to induce a drastic depletion in cellular ATP levels. Therefore, we studied the effect of methadone on isolated rat liver mitochondria. We observed that methadone caused mitochondrial uncoupling, coinciding with the ionophoric properties of methadone, but did not cause swelling of the organelles. Overall, the effects observed for cells in the presence of supratherapeutic doses of methadone may result from a “bioenergetic crisis.” A decreased level of cellular energy may predispose cells to necrotic-like cell death.Elsevier2010info:eu-repo/semantics/articlehttps://www.scopus.com/record/display.uri?eid=2-s2.0-77956647666&origin=inward&txGid=37fa75acb8aa751c9c0b7a7a8d5643a8https://pubmed.ncbi.nlm.nih.gov/20691259/http://hdl.handle.net/20.500.12020/1231reponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/12312026-05-27T07:36:51Z
dc.title.none.fl_str_mv Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
title Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
spellingShingle Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
Perez-Alvarez, Sergio
Biología Celular y Molecular
Ciencias Biomédicas
Bax
Clark electrode
Methadone
Mitochondria
Necrosis
Neurodegeneration
32 Ciencias Médicas
title_short Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
title_full Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
title_fullStr Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
title_full_unstemmed Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
title_sort Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis
dc.creator.none.fl_str_mv Perez-Alvarez, Sergio
Cuenca-Lopez, Maria D.
Melero Fernandez de Mera, Raquel Maria
Puerta, Elena
Karachitos, Andonis
Bednarczyk, Piotr
Kmita, Hanna
Aguirre, Norberto
Galindo, Maria F
Jordán, Joaquin
author Perez-Alvarez, Sergio
author_facet Perez-Alvarez, Sergio
Cuenca-Lopez, Maria D.
Melero Fernandez de Mera, Raquel Maria
Puerta, Elena
Karachitos, Andonis
Bednarczyk, Piotr
Kmita, Hanna
Aguirre, Norberto
Galindo, Maria F
Jordán, Joaquin
author_role author
author2 Cuenca-Lopez, Maria D.
Melero Fernandez de Mera, Raquel Maria
Puerta, Elena
Karachitos, Andonis
Bednarczyk, Piotr
Kmita, Hanna
Aguirre, Norberto
Galindo, Maria F
Jordán, Joaquin
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología Celular y Molecular
Ciencias Biomédicas
Bax
Clark electrode
Methadone
Mitochondria
Necrosis
Neurodegeneration
32 Ciencias Médicas
topic Biología Celular y Molecular
Ciencias Biomédicas
Bax
Clark electrode
Methadone
Mitochondria
Necrosis
Neurodegeneration
32 Ciencias Médicas
description Methadone is a widely used therapeutic opioid in narcotic addiction and neuropathic pain syndromes. Oncologists regularly use methadone as a long-lasting analgesic. Recently it has also been proposed as a promising agent in leukemia therapy, especially when conventional therapies are not effective. Nevertheless, numerous reports indicate a negative impact on human cognition with chronic exposure to opiates. Thus, clarification of methadone toxicity is required. In SH-SY5Y cells we found that high concentrations of methadone were required to induce cell death. Methadone-induced cell death seems to be related to necrotic processes rather than typical apoptosis. Cell cultures challenged with methadone presented alterations in mitochondrial outer membrane permeability. A mechanism that involves Bax translocation to the mitochondria was observed, accompanied with cytochrome c release. Furthermore, no participation of known protein regulators of apoptosis such as Bcl-XL and p53 was observed. Interestingly, methadone induced cell death took place by a caspases-independent pathway; perhaps due to its ability to induce a drastic depletion in cellular ATP levels. Therefore, we studied the effect of methadone on isolated rat liver mitochondria. We observed that methadone caused mitochondrial uncoupling, coinciding with the ionophoric properties of methadone, but did not cause swelling of the organelles. Overall, the effects observed for cells in the presence of supratherapeutic doses of methadone may result from a “bioenergetic crisis.” A decreased level of cellular energy may predispose cells to necrotic-like cell death.
publishDate 2010
dc.date.none.fl_str_mv 2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.scopus.com/record/display.uri?eid=2-s2.0-77956647666&origin=inward&txGid=37fa75acb8aa751c9c0b7a7a8d5643a8
https://pubmed.ncbi.nlm.nih.gov/20691259/
http://hdl.handle.net/20.500.12020/1231
url https://www.scopus.com/record/display.uri?eid=2-s2.0-77956647666&origin=inward&txGid=37fa75acb8aa751c9c0b7a7a8d5643a8
https://pubmed.ncbi.nlm.nih.gov/20691259/
http://hdl.handle.net/20.500.12020/1231
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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