Effect of 5-aminolevulinic acid on the expression of carcinogenesis-related proteins in cultured primary hepatocytes

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dc.contributorLaboratório de Biologia Molecularpt_BR
dc.contributor.authorMenezes, Patrícia Reginapt_BR
dc.contributor.authorGonzález, Carlos Andreypt_BR
dc.contributor.authorde Souza, Ana Olíviapt_BR
dc.contributor.authorMaria, Durvanei Augustopt_BR
dc.contributor.authorOnuki, Janicept_BR
dc.date.accessioned2020-07-09T21:22:21Z-
dc.date.available2020-07-09T21:22:21Z-
dc.date.issued2018-
dc.identifier.citationMenezes PR, González CA, de Souza AO, Maria DA, Onuki J. Effect of 5-aminolevulinic acid on the expression of carcinogenesis-related proteins in cultured primary hepatocytes. Mol. Biol. Rep.. 2018 Dec;45(6):2801-9. doi:10.1007/s11033-018-4367-5.pt_BR
dc.identifier.issn0301-4851-
dc.identifier.issn1573-4978-
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2632-
dc.description.abstractAcute intermittent porphyria (AIP) is a heme pathway disorder caused by a decrease in the activity and synthesis of porphobilinogen deaminase. Thus, the first heme precursor 5-aminolevulinic acid (ALA) accumulates in the liver. Reactive oxygen species (ROS) resulting from ALA oxidation may be correlated to a higher incidence of hepatocellular carcinoma (HCC) in AIP patients. However, the molecular mechanisms of this relationship have not been thoroughly elucidated to date. In this study, we investigated the effect of increasing levels of ALA on the expression of proteins related to DNA repair, oxidative stress, apoptosis, proliferation and lipid metabolism. Primary rat hepatocytes were isolated by the collagenase perfusion method, lipoperoxidation was evaluated by a TBA fluorimetric assay and Western blotting was used to assess protein abundance. The data showed that ALA treatment promoted a dose-dependent increase of p53 expression, downregulation of Bcl-2, HMG-CoA reductase and OGG1 and an increase in lipoperoxidation. There was no alteration in the expression of the transcription factor NF-?B, catalase and superoxide dismutase. ALA oxidation products induced protein regulation patterns, suggesting the interconnection of cellular processes, such as the intrinsic pathway of apoptosis, redox homeostasis, cell proliferation, lipid metabolism and DNA repair. This study helps to elucidate the molecular mechanisms of hepatotoxicity mediated by ALA pro-oxidant effects and supports the hypothesis that ALA accumulation correlates with a higher incidence of hepatic carcinogenic events.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.format.extentp. 2801-2809pt_BR
dc.languageengpt_BR
dc.publisherSpringerpt_BR
dc.relation.ispartofMolecular Biology Reportspt_BR
dc.titleEffect of 5-aminolevulinic acid on the expression of carcinogenesis-related proteins in cultured primary hepatocytespt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1007/s11033-018-4367-5pt_BR
dc.identifier.urlhttps://doi.org/10.1007/s11033-018-4367-5pt_BR
dc.contributor.externalUniversidade de São Paulo (USP)¦¦Brasilpt_BR
dc.contributor.externalOrganismo de Investigación Judicial (OIJ)¦¦Costa Ricapt_BR
dc.publisher.cityDordrechtpt_BR
dc.identifier.citationvolume45pt_BR
dc.identifier.citationissue6pt_BR
dc.subject.keyword5-Aminolevulinic acidpt_BR
dc.subject.keywordAcute intermittent porphyriapt_BR
dc.subject.keywordHepatocellular carcinomapt_BR
dc.subject.keywordProtein expressionpt_BR
dc.subject.keywordReactive oxygen speciespt_BR
dc.subject.keywordPrimary rat hepatocytespt_BR
dc.relation.ispartofabbreviatedMol. Biol. Rep.pt_BR
dc.identifier.citationabntv. 45, n. 6, p. 2801-2809, dez. 2018pt_BR
dc.identifier.citationvancouver2018 Dec;45(6):2801-9pt_BR
dc.publisher.countryNetherlandspt_BR
dc.contributor.butantanGonzález, Carlos Andrey|:Aluno|:Laboratório de Biologia Molecular|:pt_BR
dc.contributor.butantande Souza, Ana Olívia|:Pesquisador|:Laboratório de Biologia Molecular|:pt_BR
dc.contributor.butantanMaria, Durvanei Augusto|:Pesquisador|:Laboratório de Biologia Molecular|:pt_BR
dc.contributor.butantanOnuki, Janice|:Pesquisador|:Laboratório de Biologia Molecular|:Autor de correspondênciapt_BR
dc.contributor.butantanMenezes, Patrícia Regina|:Aluno|:Laboratório de Biologia Molecular|:PrimeiroAutorpt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦USP-33002010156POpt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦07/01966-5, 10/51068-6pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
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