Impact of high glucose and AGEs on cultured kidney-derived cells. Effects on cell viability, lysosomal enzymes and effectors of cell signaling pathways

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dc.citation.volume135
dc.contributor.authorPeres, Giovani B. [UNIFESP]
dc.contributor.authorSchor, Nestor [UNIFESP]
dc.contributor.authorMichelacci, Yara M. [UNIFESP]
dc.coverageParis
dc.date.accessioned2020-07-17T14:02:32Z
dc.date.available2020-07-17T14:02:32Z
dc.date.issued2017
dc.description.abstractWe have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied. HG increased viable mesangial cells (ihMC) in 48 h, while epithelial tubular cells were not affected (LLC-PK1 and MDCK). In contrast, the number of viable cells was markedly decreased, for all cell lines, by AGE-BSA. Concerning lysosomal enzymes, the main cysteine-protease expressed by these cells was cathepsin B, and its concentration was much higher in epithelial than in mesangial cells. Exposure to HG had no effect on the cathepsin B activity, but AGE-BSA caused a marked decrease in LLC-PK1, and increased the enzyme activities in the other cell lines. The levels of nitric oxide (NO) was increased by AGE-BSA in all cell lines, suggesting oxidative stress, and Western blotting has shown that, among the investigated proteins, cathepsin B, mTOR and transcription factor EB (TFEB) were the most significantly affected by exposure to AGE-BSA. As mTOR induces anabolism and inhibits autophagy, and TFEB is a master transcription factor for lysosomal enzymes, it is possible that this pathway plays a role in the inhibition of lysosomal enzymes in proximal tubule cells. Published by Elsevier B.V.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Med, Disciplina Nefrol, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Med, Disciplina Nefrol, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipSao Paulo, SP, Brazil
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipBrasilia, DF, Brazil
dc.description.sponsorshipFundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brasilia, SP, Brazil
dc.description.sponsorshipIDFAPESP: 2010/16022-5
dc.description.sponsorshipIDFAPESP: 2013/07109-8
dc.description.sponsorshipIDFAPESP: 2015/03964-6
dc.description.sponsorshipIDCNPq: 301326/2013-4
dc.format.extent137-148
dc.identifierhttp://dx.doi.org/10.1016/j.biochi.2017.02.004
dc.identifier.citationBiochimie. Paris, v. 135, p. 137-148, 2017.
dc.identifier.doi10.1016/j.biochi.2017.02.004
dc.identifier.issn0300-9084
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54852
dc.identifier.wosWOS:000397694600016
dc.language.isoeng
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartofBiochimie
dc.rightsAcesso restrito
dc.subjectDiabetes mellitusen
dc.subjectLysosomal enzymesen
dc.subjectAdvanced glycation end productsen
dc.subjectLLC-PK1en
dc.subjectMDCKen
dc.subjectihMCen
dc.titleImpact of high glucose and AGEs on cultured kidney-derived cells. Effects on cell viability, lysosomal enzymes and effectors of cell signaling pathwaysen
dc.typeArtigo
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