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Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines

OBJECTIVE: Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of...

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Autores principales: Sagarkar, Sneha, Gandhi, Deepa, Devi, S. Saravana, Sakharkar, Amul, Kapley, Atya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825440/
https://www.ncbi.nlm.nih.gov/pubmed/27114639
http://dx.doi.org/10.4103/0253-7613.178842
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author Sagarkar, Sneha
Gandhi, Deepa
Devi, S. Saravana
Sakharkar, Amul
Kapley, Atya
author_facet Sagarkar, Sneha
Gandhi, Deepa
Devi, S. Saravana
Sakharkar, Amul
Kapley, Atya
author_sort Sagarkar, Sneha
collection PubMed
description OBJECTIVE: Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure. MATERIALS AND METHODS: We have determined the EC(50) values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction. RESULTS: The EC(50) value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors’ expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines. CONCLUSION: Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity.
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spelling pubmed-48254402016-04-25 Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines Sagarkar, Sneha Gandhi, Deepa Devi, S. Saravana Sakharkar, Amul Kapley, Atya Indian J Pharmacol Research Article OBJECTIVE: Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure. MATERIALS AND METHODS: We have determined the EC(50) values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction. RESULTS: The EC(50) value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors’ expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines. CONCLUSION: Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity. Medknow Publications & Media Pvt Ltd 2016 /pmc/articles/PMC4825440/ /pubmed/27114639 http://dx.doi.org/10.4103/0253-7613.178842 Text en Copyright: © Indian Journal of Pharmacology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Research Article
Sagarkar, Sneha
Gandhi, Deepa
Devi, S. Saravana
Sakharkar, Amul
Kapley, Atya
Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
title Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
title_full Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
title_fullStr Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
title_full_unstemmed Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
title_short Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
title_sort atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825440/
https://www.ncbi.nlm.nih.gov/pubmed/27114639
http://dx.doi.org/10.4103/0253-7613.178842
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