Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/110215
DC FieldValueLanguage
dc.contributor.authorBento, Carla Figueira-
dc.contributor.authorMarques, Filipa-
dc.contributor.authorFernandes, Rosa-
dc.contributor.authorPereira, Paulo-
dc.date.accessioned2023-11-20T09:47:18Z-
dc.date.available2023-11-20T09:47:18Z-
dc.date.issued2010-09-24-
dc.identifier.issn1932-6203pt
dc.identifier.urihttps://hdl.handle.net/10316/110215-
dc.description.abstractBackground: Increased production and accumulation of methylglyoxal (MGO), as well as increased modification of proteins by glycoxidation, are hallmarks of aging and diabetes. MGO was shown to modify proteins and to contribute to the accumulation of damaged proteins that can be toxic to cells. However, the effect of MGO on the cell systems responsible for repairing or degrading damaged proteins is still unclear. In this study, the effect of MGO on the function of the ubiquitinproteasome system (UPS) and on molecular chaperones, two cooperative mechanisms associated with protein quality control, was investigated. Principal Findings: In this work it is shown that treatment of cells with MGO leads to accumulation of ubiquitin conjugates and depletion of free ubiquitin. Moreover, MGO significantly decreases the proteolytic activity of the 20S proteasome. Data further shows that MGO decreases the levels of the molecular chaperones Hsc70 and Hsp90 and leads to accumulation of CHIP-, Hsp40- and ubiquitin-containing aggregates. The formation of large aggregates containing CHIP is a consequence of its binding to misfolded proteins and to molecular chaperones. Moreover, dysfunction of the chaperones/CHIP/UPS axis is associated with accumulation of oxidized and argpyrimidine-modified proteins, which is likely to be associated with decreased cell viability. Interestingly, data further shows that MGO-induced stress induces the activation of heat shock factor-1 (Hsf-1), the main transcription factor involved in the regulation of the expression of heat shock proteins (HSPs) and cell response to stress. Conclusions: The data obtained in this work suggests that MGO impairs both the UPS and the protein quality control dependent on CHIP and molecular chaperones, leading to accumulation of toxic aggregates and increased cell death. However, these MGO-induced changes appear to elicit a response from the Hsf-1 system, which is crucial to help cells to cope with cellular stress and to re-establish homeostasis.pt
dc.language.isoengpt
dc.publisherPublic Library of Sciencept
dc.relationSFRH/BD/15229/2004pt
dc.relationPOCI/SAU-OBS/57772/2004pt
dc.relationPDTC/SAU-OBS/ 67498/2006pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subject.meshHumanspt
dc.subject.meshMolecular Chaperonespt
dc.subject.meshProteasome Endopeptidase Complexpt
dc.subject.meshProtein Foldingpt
dc.subject.meshProtein Processing, Post-Translationalpt
dc.subject.meshProtein Stabilitypt
dc.subject.meshProteinspt
dc.subject.meshPyruvaldehydept
dc.subject.meshUbiquitinpt
dc.titleMethylglyoxal alters the function and stability of critical components of the protein quality controlpt
dc.typearticle-
degois.publication.firstPagee13007pt
degois.publication.issue9pt
degois.publication.titlePLoS ONEpt
dc.peerreviewedyespt
dc.identifier.doi10.1371/journal.pone.0013007pt
degois.publication.volume5pt
dc.date.embargo2010-09-24*
uc.date.periodoEmbargo0pt
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypearticle-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.fulltextCom Texto completo-
item.languageiso639-1en-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0001-7828-2296-
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
Show simple item record

Google ScholarTM

Check

Altmetric

Altmetric


This item is licensed under a Creative Commons License Creative Commons