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Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine

2015Journal article Open access
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dc.contributor.authorFernandes, Sílvia
dc.contributor.authorSalta, Sofia
dc.contributor.authorSummavielle, Teresa
dc.date.accessioned2015-06-04T08:33:50Z
dc.date.available2016-01-01T01:30:13Z
dc.date.issued2015
dc.description.abstractMethamphetamine (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.por
dc.identifier.citationFernandes, 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
dc.identifier.doi10.1016/j.toxlet.2015.02.011
dc.identifier.urihttp://hdl.handle.net/10400.22/6221
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0378427415000788por
dc.subjectCytoskeletonpor
dc.subjecta-Tubulinpor
dc.subjectMethamphetaminepor
dc.subjectAcetyl-L-carnitinepor
dc.subjectHistone deacetylasepor
dc.titleMethamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitinepor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage138por
oaire.citation.startPage131por
oaire.citation.titleToxicology Letterspor
oaire.citation.volume234por
person.familyNameFernandes
person.familyNameSalta
person.familyNameSummavielle
person.givenNameSílvia
person.givenNameSofia
person.givenNameTeresa
person.identifier212663
person.identifier677706
person.identifier.ciencia-idFB1A-1376-32B8
person.identifier.ciencia-id6119-2B18-6A26
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.orcid0000-0003-2031-0658
person.identifier.orcid0000-0002-6707-1263
person.identifier.orcid0000-0003-2548-6281
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id57195931190
person.identifier.scopus-author-id56436611200
person.identifier.scopus-author-id6603092949
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationa15c298e-1ac3-4aac-855c-ec6acbc30e25
relation.isAuthorOfPublicationfea3c2c5-1c3c-46ef-943c-1603ef3efc27
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublication.latestForDiscoverya15c298e-1ac3-4aac-855c-ec6acbc30e25

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