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Involvement of endoplasmic reticulum and autophagy in microcystin-LR toxicity in Vero-E6 and HepG2 cell lines

dc.contributor.authorMenezes, Carina
dc.contributor.authorAlverca, Elsa
dc.contributor.authorDias, Elsa
dc.contributor.authorSam-Bento, Filomena
dc.contributor.authorPereira, Paulo
dc.date.accessioned2012-11-28T11:39:47Z
dc.date.available2012-11-28T11:39:47Z
dc.date.issued2012-09-23
dc.descriptionPublicação impressa do artigo em: Toxicology in Vitro. Feb 2013; 27(1): 138–148por
dc.description.abstractThis work investigates the involvement of the endoplasmic reticulum (ER) and autophagy in microcystin-LR (MCLR) toxicity in Vero-E6 and HepG2 cell lines. Additionally, morphological alterations induced by MCLR in lysosomes and mitochondria were studied. Cytotoxicity evaluation showed that pure MCLR and MCLR from LMECYA110 extract induce concentration dependent viability decays after 24 h exposure. HepG2 cells showed an increased sensitivity to MCLR than Vero cells, with lower cytotoxic thresholds and EC50 values. Conversely, LC3B immunofluorescence showed that autophagy is triggered in both cell lines as a survival response to low MCLR concentrations. Furthermore, MCLR induced a MCLR concentration-dependent decrease of GRP94 expression in HepG2 cells while in Vero cells no alteration was observed. This suggests the involvement of the ER in HepG2 apoptosis elicited by MCLR, while in Vero cells ER destructuration could be a consequence of cytoskeleton inflicted damages. Additionally, in both cell lines, lysosomal destabilization preceded mitochondrial impairment which occurred at high toxin concentrations. Although not an early cellular target of MCLR, mitochondria appears to serve as central mediators of different signaling pathways elicited by the organelles involved in MCLR toxicity. As a result, kidney and hepatic cell lines exhibit cell type and dose-dependent mechanisms to overcome MCLR toxicity.por
dc.identifier.citationToxicol In Vitro. 2012 Sep 23. pii: S0887-2333(12)00263-9. doi: 10.1016/j.tiv.2012.09.009. [Epub ahead of print]por
dc.identifier.issn0887-2333
dc.identifier.otherESSN: 1879-3177
dc.identifier.otherdoi: 10.1016/j.tiv.2012.09.009
dc.identifier.urihttp://hdl.handle.net/10400.18/1123
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0887233312002639por
dc.subjectMicrocystin-LRpor
dc.subjectVero-E6 Cellspor
dc.subjectHepG2 Cellspor
dc.subjectAutophagypor
dc.subjectLysosomespor
dc.subjectEndoplasmic Reticulumpor
dc.subjectÁgua e Solopor
dc.titleInvolvement of endoplasmic reticulum and autophagy in microcystin-LR toxicity in Vero-E6 and HepG2 cell linespor
dc.typejournal article
dspace.entity.typePublication
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor

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