Non-lethal concentration of MeHg causes marked responses in the DNA repair, integrity, and replication pathways in the exposed human salivary gland cell line
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
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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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 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
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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eng |
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eng |
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openAccess |
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Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
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