Cargando…

Non-Lethal Concentration of MeHg Causes Marked Responses in the DNA Repair, Integrity, and Replication Pathways in the Exposed Human Salivary Gland Cell Line

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 alteration...

Descripción completa

Detalles Bibliográficos
Autores principales: Nogueira, Lygia Sega, Vasconcelos, Carolina P., Plaça, Jessica Rodrigues, Mitre, Geovanni Pereira, Bittencourt, Leonardo Oliveira, Kataoka, Maria Sueli da Silva, de Oliveira, Edivaldo H. C., Lima, Rafael Rodrigues
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423918/
https://www.ncbi.nlm.nih.gov/pubmed/34512333
http://dx.doi.org/10.3389/fphar.2021.698671
_version_ 1783749563114323968
author Nogueira, Lygia Sega
Vasconcelos, Carolina P.
Plaça, Jessica Rodrigues
Mitre, Geovanni Pereira
Bittencourt, Leonardo Oliveira
Kataoka, Maria Sueli da Silva
de Oliveira, Edivaldo H. C.
Lima, Rafael Rodrigues
author_facet Nogueira, Lygia Sega
Vasconcelos, Carolina P.
Plaça, Jessica Rodrigues
Mitre, Geovanni Pereira
Bittencourt, Leonardo Oliveira
Kataoka, Maria Sueli da Silva
de Oliveira, Edivaldo H. C.
Lima, Rafael Rodrigues
author_sort Nogueira, Lygia Sega
collection PubMed
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.
format Online
Article
Text
id pubmed-8423918
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84239182021-09-09 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 Vasconcelos, Carolina P. Plaça, Jessica Rodrigues Mitre, Geovanni Pereira Bittencourt, Leonardo Oliveira Kataoka, Maria Sueli da Silva de Oliveira, Edivaldo H. C. Lima, Rafael Rodrigues Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-08-25 /pmc/articles/PMC8423918/ /pubmed/34512333 http://dx.doi.org/10.3389/fphar.2021.698671 Text en Copyright © 2021 Nogueira, Vasconcelos, Plaça, Mitre, Bittencourt, Kataoka, de Oliveira and Lima. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Nogueira, Lygia Sega
Vasconcelos, Carolina P.
Plaça, Jessica Rodrigues
Mitre, Geovanni Pereira
Bittencourt, Leonardo Oliveira
Kataoka, Maria Sueli da Silva
de Oliveira, Edivaldo H. C.
Lima, Rafael Rodrigues
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
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_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_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
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423918/
https://www.ncbi.nlm.nih.gov/pubmed/34512333
http://dx.doi.org/10.3389/fphar.2021.698671
work_keys_str_mv AT nogueiralygiasega nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT vasconceloscarolinap nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT placajessicarodrigues nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT mitregeovannipereira nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT bittencourtleonardooliveira nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT kataokamariasuelidasilva nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT deoliveiraedivaldohc nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline
AT limarafaelrodrigues nonlethalconcentrationofmehgcausesmarkedresponsesinthednarepairintegrityandreplicationpathwaysintheexposedhumansalivaryglandcellline