Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line

Detalhes bibliográficos
Autor(a) principal: Nogueira, Lygia Sega
Data de Publicação: 2021
Outros Autores: Vasconcelos, Carolina P, Plaça, Jessica Rodrigues, Mitre, Geovanni Pereira, Bittencourt, Leonardo Oliveira, Kataoka, Maria Sueli da Silva, Oliveira, Edivaldo Herculano Corrêa de, Lima, Rafael Rodrigues
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/4505
Resumo: In Brazilian northern Amazon, communities are potentially exposed and vulnerable to methylmercury (MeHg) toxicity through the vast ingestion of fish. In vivo and in vitro studies demonstrated that the salivary glands as a susceptible organ to this potent environmental pollutant, reporting alterations on physiological, biochemical, and proteomic parameters. However, the alterations caused by MeHg on the gene expression of the exposed human salivary gland cells are still unknown. Therefore, the goal was to perform the transcriptome profile of the human salivary gland cell line after exposure to MeHg, using the microarray technique and posterior bioinformatics analysis. The cell exposure was performed using 2.5 µM MeHg. A previously published study demonstrated that this concentration belongs to a range of concentrations that caused biochemical and metabolic alterations in this linage. As a result, the MeHg exposure did not cause lethality in the human salivary gland cells line but was able to alter the expression of 155 genes. Downregulated genes (15) are entirety relating to the cell metabolism impairment, and according to KEGG analysis, they belong to the glycosphingolipid (GSL) biosynthesis pathway. On the other hand, most of the 140 upregulated genes were related to cell-cycle progression, DNA repair, and replication pathway, or cellular defenses through the GSH basal metabolism. These genomic changes revealed the effort to the cell to maintain physiological and genomic stability to avoid cell death, being in accordance with the nonlethality in the toxicity test. Last, the results support in-depth studies on nonlethal MeHg concentrations for biomarkers identification that interpret transcriptomics data in toxicological tests serving as an early alert of physiological changes in vitro biological models.
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spelling Nogueira, Lygia SegaVasconcelos, Carolina PPlaça, Jessica RodriguesMitre, Geovanni PereiraBittencourt, Leonardo OliveiraKataoka, Maria Sueli da SilvaOliveira, Edivaldo Herculano Corrêa deLima, Rafael Rodrigues2022-05-16T13:36:15Z2022-05-16T13:36:15Z2021NOGUEIRA, Lygia Sega et al. Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line. Frontiers in Pharmacology, v. 12, n. 698671, p. 1-8, Aug. 2021.1663-9812https://patua.iec.gov.br/handle/iec/450510.3389/fphar.2021.698671In Brazilian northern Amazon, communities are potentially exposed and vulnerable to methylmercury (MeHg) toxicity through the vast ingestion of fish. In vivo and in vitro studies demonstrated that the salivary glands as a susceptible organ to this potent environmental pollutant, reporting alterations on physiological, biochemical, and proteomic parameters. However, the alterations caused by MeHg on the gene expression of the exposed human salivary gland cells are still unknown. Therefore, the goal was to perform the transcriptome profile of the human salivary gland cell line after exposure to MeHg, using the microarray technique and posterior bioinformatics analysis. The cell exposure was performed using 2.5 µM MeHg. A previously published study demonstrated that this concentration belongs to a range of concentrations that caused biochemical and metabolic alterations in this linage. As a result, the MeHg exposure did not cause lethality in the human salivary gland cells line but was able to alter the expression of 155 genes. Downregulated genes (15) are entirety relating to the cell metabolism impairment, and according to KEGG analysis, they belong to the glycosphingolipid (GSL) biosynthesis pathway. On the other hand, most of the 140 upregulated genes were related to cell-cycle progression, DNA repair, and replication pathway, or cellular defenses through the GSH basal metabolism. These genomic changes revealed the effort to the cell to maintain physiological and genomic stability to avoid cell death, being in accordance with the nonlethality in the toxicity test. Last, the results support in-depth studies on nonlethal MeHg concentrations for biomarkers identification that interpret transcriptomics data in toxicological tests serving as an early alert of physiological changes in vitro biological models.Brazilian National Council for Scientific and Technological Development (CNPq); Brazilian Government/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Finance Code 001 and Programa Nacional de Pós Doutorado/Capes (PNPD/CAPES). The APC was funded by Pró-Reitoria de Pesquisa e Pós-graduação da Universidade Federal do Pará (PROPESP-UFPA).Federal University of Pará. Laboratory of Functional and Structural Biology. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura Celular e Citogenética. Ananindeua, PA, BrasilUniversity of São Paulo. Medical School. University Hospital of the Ribeirão Preto. Regional Blood Center. Ribeirão Preto, SP, BrazilFederal University of Pará. School of Dentistry. Belém, PA, BrazilFederal University of Pará. Laboratory of Functional and Structural Biology. Belém, PA, BrazilFederal University of Pará. School of Dentistry. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura Celular e Citogenética. Ananindeua, PA, BrasilFederal University of Pará. Laboratory of Functional and Structural Biology. Belém, PA, BrazilengFrontiers MediaNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell lineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleGlândulas Salivares / ultraestruturaGlândulas Salivares / fisiologiaCompostos de Metilmercúrio / químicaCompostos de Metilmercúrio / toxicidadeTranscriptomaBiomarcadores / análiseinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECLICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/47c3cd21-069e-4a7e-a086-659d1da13bdd/download11832eea31b16df8613079d742d61793MD52ORIGINALNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line.pdfNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line.pdfapplication/pdf1309195https://patua.iec.gov.br/bitstreams/9640b6b0-7717-41fb-8708-f93b22116fd2/downloaddff541c08d3aa5d028adb49876b1cf2fMD51TEXTNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line.pdf.txtNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line.pdf.txtExtracted texttext/plain41325https://patua.iec.gov.br/bitstreams/bcdabe35-3675-4804-acef-e5f2252ff448/download6870de6e0192f2e40b923d4acec5ed58MD55THUMBNAILNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line.pdf.jpgNon-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line.pdf.jpgGenerated Thumbnailimage/jpeg5809https://patua.iec.gov.br/bitstreams/1d939e74-cefe-457a-b602-5959bbac99d0/download851a6c02a7533fbaffbb64d960e995f2MD56iec/45052022-10-20 21:21:49.609oai:patua.iec.gov.br:iec/4505https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T21:21:49Repositório Digital do Instituto Evandro Chagas (Patuá) - 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dc.title.pt_BR.fl_str_mv Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
title Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
spellingShingle Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
Nogueira, Lygia Sega
Glândulas Salivares / ultraestrutura
Glândulas Salivares / fisiologia
Compostos de Metilmercúrio / química
Compostos de Metilmercúrio / toxicidade
Transcriptoma
Biomarcadores / análise
title_short Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
title_full Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
title_fullStr Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
title_full_unstemmed Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
title_sort Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
author Nogueira, Lygia Sega
author_facet Nogueira, Lygia Sega
Vasconcelos, Carolina P
Plaça, Jessica Rodrigues
Mitre, Geovanni Pereira
Bittencourt, Leonardo Oliveira
Kataoka, Maria Sueli da Silva
Oliveira, Edivaldo Herculano Corrêa de
Lima, Rafael Rodrigues
author_role author
author2 Vasconcelos, Carolina P
Plaça, Jessica Rodrigues
Mitre, Geovanni Pereira
Bittencourt, Leonardo Oliveira
Kataoka, Maria Sueli da Silva
Oliveira, Edivaldo Herculano Corrêa de
Lima, Rafael Rodrigues
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Nogueira, Lygia Sega
Vasconcelos, Carolina P
Plaça, Jessica Rodrigues
Mitre, Geovanni Pereira
Bittencourt, Leonardo Oliveira
Kataoka, Maria Sueli da Silva
Oliveira, Edivaldo Herculano Corrêa de
Lima, Rafael Rodrigues
dc.subject.decsPrimary.pt_BR.fl_str_mv Glândulas Salivares / ultraestrutura
Glândulas Salivares / fisiologia
Compostos de Metilmercúrio / química
Compostos de Metilmercúrio / toxicidade
Transcriptoma
Biomarcadores / análise
topic Glândulas Salivares / ultraestrutura
Glândulas Salivares / fisiologia
Compostos de Metilmercúrio / química
Compostos de Metilmercúrio / toxicidade
Transcriptoma
Biomarcadores / análise
description In Brazilian northern Amazon, communities are potentially exposed and vulnerable to methylmercury (MeHg) toxicity through the vast ingestion of fish. In vivo and in vitro studies demonstrated that the salivary glands as a susceptible organ to this potent environmental pollutant, reporting alterations on physiological, biochemical, and proteomic parameters. However, the alterations caused by MeHg on the gene expression of the exposed human salivary gland cells are still unknown. Therefore, the goal was to perform the transcriptome profile of the human salivary gland cell line after exposure to MeHg, using the microarray technique and posterior bioinformatics analysis. The cell exposure was performed using 2.5 µM MeHg. A previously published study demonstrated that this concentration belongs to a range of concentrations that caused biochemical and metabolic alterations in this linage. As a result, the MeHg exposure did not cause lethality in the human salivary gland cells line but was able to alter the expression of 155 genes. Downregulated genes (15) are entirety relating to the cell metabolism impairment, and according to KEGG analysis, they belong to the glycosphingolipid (GSL) biosynthesis pathway. On the other hand, most of the 140 upregulated genes were related to cell-cycle progression, DNA repair, and replication pathway, or cellular defenses through the GSH basal metabolism. These genomic changes revealed the effort to the cell to maintain physiological and genomic stability to avoid cell death, being in accordance with the nonlethality in the toxicity test. Last, the results support in-depth studies on nonlethal MeHg concentrations for biomarkers identification that interpret transcriptomics data in toxicological tests serving as an early alert of physiological changes in vitro biological models.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2022-05-16T13:36:15Z
dc.date.available.fl_str_mv 2022-05-16T13:36:15Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv NOGUEIRA, Lygia Sega et al. Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line. Frontiers in Pharmacology, v. 12, n. 698671, p. 1-8, Aug. 2021.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/4505
dc.identifier.issn.-.fl_str_mv 1663-9812
dc.identifier.doi.-.fl_str_mv 10.3389/fphar.2021.698671
identifier_str_mv NOGUEIRA, Lygia Sega et al. Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line. Frontiers in Pharmacology, v. 12, n. 698671, p. 1-8, Aug. 2021.
1663-9812
10.3389/fphar.2021.698671
url https://patua.iec.gov.br/handle/iec/4505
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