Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.22/6221 |
Resumo: | Methamphetamine (METH) is a powerful psychostimulant drug used worldwide for its reinforcing properties. In addition to the classic long-lasting monoaminergic-disrupting effects extensively described in the literature, METH has been consistently reported to increase blood brain barrier (BBB) permeability, both in vivo and in vitro, as a result of tight junction and cytoskeleton disarrangement. Microtubules play a critical role in cell stability, which relies on post-translational modifications such as a-tubulin acetylation. As there is evidence that psychostimulants drugs modulate the expression of histone deacetylases (HDACs), we hypothesized that in endothelial cells METH-mediation of cytoplasmatic HDAC6 activity could affect tubulin acetylation and further contribute to BBB dysfunction. To validate our hypothesis, we exposed the bEnd.3 endothelial cells to increasing doses of METH and verified that itleads to an extensivea-tubulin deacetylation mediated by HDACs activation. Furthermore, since we recently reported that acetyl-L-carnitine (ALC), a natural occurring compound, prevents BBB structural loss in a context of METH exposure, we reasoned that ALC could also preserve the acetylation of microtubules under METH action. The present results confirm that ALC is able to prevent METH-induced deacetylation providing effective protection on microtubule acetylation. Although further investigation is still needed, HDACs regulation may become a new therapeutic target for ALC. |
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Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitineCytoskeletona-TubulinMethamphetamineAcetyl-L-carnitineHistone deacetylaseMethamphetamine (METH) is a powerful psychostimulant drug used worldwide for its reinforcing properties. In addition to the classic long-lasting monoaminergic-disrupting effects extensively described in the literature, METH has been consistently reported to increase blood brain barrier (BBB) permeability, both in vivo and in vitro, as a result of tight junction and cytoskeleton disarrangement. Microtubules play a critical role in cell stability, which relies on post-translational modifications such as a-tubulin acetylation. As there is evidence that psychostimulants drugs modulate the expression of histone deacetylases (HDACs), we hypothesized that in endothelial cells METH-mediation of cytoplasmatic HDAC6 activity could affect tubulin acetylation and further contribute to BBB dysfunction. To validate our hypothesis, we exposed the bEnd.3 endothelial cells to increasing doses of METH and verified that itleads to an extensivea-tubulin deacetylation mediated by HDACs activation. Furthermore, since we recently reported that acetyl-L-carnitine (ALC), a natural occurring compound, prevents BBB structural loss in a context of METH exposure, we reasoned that ALC could also preserve the acetylation of microtubules under METH action. The present results confirm that ALC is able to prevent METH-induced deacetylation providing effective protection on microtubule acetylation. Although further investigation is still needed, HDACs regulation may become a new therapeutic target for ALC.ElsevierRepositório Científico do Instituto Politécnico do PortoFernandes, SílviaSalta, SofiaSummavielle, Teresa2016-01-01T01:30:13Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/6221engFernandes, S., Salta, S., & Summavielle, T. (2015). Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine. Toxicology Letters, 234, 131–138. https://doi.org/10.1016/j.toxlet.2015.02.01110.1016/j.toxlet.2015.02.011info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-20T01:52:55Zoai:recipp.ipp.pt:10400.22/6221Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:26:47.560021Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
title |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
spellingShingle |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine Fernandes, Sílvia Cytoskeleton a-Tubulin Methamphetamine Acetyl-L-carnitine Histone deacetylase |
title_short |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
title_full |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
title_fullStr |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
title_full_unstemmed |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
title_sort |
Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine |
author |
Fernandes, Sílvia |
author_facet |
Fernandes, Sílvia Salta, Sofia Summavielle, Teresa |
author_role |
author |
author2 |
Salta, Sofia Summavielle, Teresa |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Fernandes, Sílvia Salta, Sofia Summavielle, Teresa |
dc.subject.por.fl_str_mv |
Cytoskeleton a-Tubulin Methamphetamine Acetyl-L-carnitine Histone deacetylase |
topic |
Cytoskeleton a-Tubulin Methamphetamine Acetyl-L-carnitine Histone deacetylase |
description |
Methamphetamine (METH) is a powerful psychostimulant drug used worldwide for its reinforcing properties. In addition to the classic long-lasting monoaminergic-disrupting effects extensively described in the literature, METH has been consistently reported to increase blood brain barrier (BBB) permeability, both in vivo and in vitro, as a result of tight junction and cytoskeleton disarrangement. Microtubules play a critical role in cell stability, which relies on post-translational modifications such as a-tubulin acetylation. As there is evidence that psychostimulants drugs modulate the expression of histone deacetylases (HDACs), we hypothesized that in endothelial cells METH-mediation of cytoplasmatic HDAC6 activity could affect tubulin acetylation and further contribute to BBB dysfunction. To validate our hypothesis, we exposed the bEnd.3 endothelial cells to increasing doses of METH and verified that itleads to an extensivea-tubulin deacetylation mediated by HDACs activation. Furthermore, since we recently reported that acetyl-L-carnitine (ALC), a natural occurring compound, prevents BBB structural loss in a context of METH exposure, we reasoned that ALC could also preserve the acetylation of microtubules under METH action. The present results confirm that ALC is able to prevent METH-induced deacetylation providing effective protection on microtubule acetylation. Although further investigation is still needed, HDACs regulation may become a new therapeutic target for ALC. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2016-01-01T01:30:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.22/6221 |
url |
http://hdl.handle.net/10400.22/6221 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Fernandes, S., Salta, S., & Summavielle, T. (2015). Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine. Toxicology Letters, 234, 131–138. https://doi.org/10.1016/j.toxlet.2015.02.011 10.1016/j.toxlet.2015.02.011 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799131363135193088 |