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Neuroprotective effect of steroidal alkaloids on glutamate-induced toxicity by preserving mitochondrial membrane potential and reducing oxidative stress

2014-03Journal article Restricted access
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dc.contributor.authorTaveira, M.
dc.contributor.authorSousa, C.
dc.contributor.authorValentão, P.
dc.contributor.authorFerreres, F.
dc.contributor.authorTeixeira, João Paulo
dc.contributor.authorAndrade, P.B.
dc.date.accessioned2015-02-04T12:45:17Z
dc.date.available2015-02-04T12:45:17Z
dc.date.issued2014-03
dc.description.abstractSeveral evidences suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of several neurodegenerative diseases. The aim of this study was to investigate for the first time whether both extracts from tomato plant (Lycopersicon esculentum Mill.) leaves and their isolated steroidal alkaloids (tomatine and tomatidine) afford neuroprotective effect against glutamate-induced toxicity in SH-SY5Y neuroblastoma cells and to elucidate the mechanisms underlying this protection. Steroidal alkaloids from tomato are well known for their cholinesterases' inhibitory capacity and the results showed that both purified extracts and isolated compounds, at non-toxic concentrations for gastric (AGS), intestinal (Caco-2) and neuronal (SH-SY5Y) cells, have the capacity to preserve mitochondria membrane potential and to decrease reactive oxygen species levels of SH-SY5Y glutamate-insulted cells. Moreover, the use of specific antagonists of cholinergic receptors allowed observing that tomatine and tomatidine can interact with nicotinic receptors, specifically with the α7 type. No effect on muscarinic receptors was noticed. In addition to the selective cholinesterases' inhibition revealed by the compounds/extracts, these results provide novel and important insights into their neuroprotective mechanism. This work also demystifies the applicability of these compounds in therapeutics, by demonstrating that their toxicity was overestimated for long time.por
dc.description.sponsorshipThe authors thank Fundação para a Ciência e a Tecnologia (FCT) for grant number PEst-C/EQB/LA0006/2011, to CYTED Programme(Ref. 112RT0460) CORNUCOPIA Thematic Network and project AGL2011-23690 (CICYT). M. Taveira (SFRH/BD/62662/2009) is indebted to FCT for the grant.por
dc.identifier.citationJ Steroid Biochem Mol Biol. 2014 Mar;140:106-15. doi: 10.1016/j.jsbmb.2013.12.013. Epub 2013 Dec 24.por
dc.identifier.doi10.1016/j.jsbmb.2013.12.013
dc.identifier.issn0960-0760
dc.identifier.urihttp://hdl.handle.net/10400.18/2768
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation112RT0460- CYTED Programmepor
dc.relationStrategic Project - LA 6 - 2011-2012
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0960076013002860por
dc.subjectSteroidal Alkaloidspor
dc.subjectNeuroprotectionpor
dc.subjectOxidative Stresspor
dc.subjectMitochondrial Membrane Potentialpor
dc.subjectCholinergic Receptorspor
dc.subjectGenotoxidade Ambientalpor
dc.titleNeuroprotective effect of steroidal alkaloids on glutamate-induced toxicity by preserving mitochondrial membrane potential and reducing oxidative stresspor
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStrategic Project - LA 6 - 2011-2012
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FEQB%2FLA0006%2F2011/PT
oaire.citation.endPage115por
oaire.citation.startPage106por
oaire.citation.titleJournal of Steroid Biochemistry and Molecular Biologypor
oaire.citation.volume140por
oaire.fundingStream6820 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor
relation.isProjectOfPublicationa1a6d73d-183f-4491-b474-ede0e4238029
relation.isProjectOfPublication.latestForDiscoverya1a6d73d-183f-4491-b474-ede0e4238029

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