PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS)
Triclosan (TCS) has been widely used as an antibacterial agent for the last several decades in personal care products. The toxicological effect of TCS has attracted more and more attention of researchers. The purpose of this study is to evaluate the cytotoxic effects of TCS in HepG2 cells and to elu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Environment International |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412019330570 |
| _version_ | 1811265946090733568 |
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| author | Jing An Huixin He Weiwei Yao Yu Shang Yun Jiang Zhiqiang Yu |
| author_facet | Jing An Huixin He Weiwei Yao Yu Shang Yun Jiang Zhiqiang Yu |
| author_sort | Jing An |
| collection | DOAJ |
| description | Triclosan (TCS) has been widely used as an antibacterial agent for the last several decades in personal care products. The toxicological effect of TCS has attracted more and more attention of researchers. The purpose of this study is to evaluate the cytotoxic effects of TCS in HepG2 cells and to elucidate the molecular mechanism focusing on regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) pathway in the glycolytic metabolism. In this study, we evaluated the adverse effect of TCS exposure on cell viability, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP). In addition, the glycolysis process in HepG2 cells exposed to TCS was examined in terms of glucose consumption, lactate production and ATP generation. Furthermore, Affymetrix Human U133 plus 2.0 gene chips and gene function enrichment analysis were conducted to screen differential expression genes (DEGs) and potential signaling pathway. Expressions of the glycolysis-related proteins were measured and quantified with Western Blotting. The results showed that TCS could suppress the cell viability, induce oxidative stress, and cause mitochondrial damage. In addition, TCS exposure promoted the glycolysis process, as manifested by accelerated conversion of glucose to lactate and increased energy release. Western Blotting results confirmed that the expression levels of glycolysis related proteins were significantly elevated. The PI3K/Akt/FoxO pathway was identified to play a pivot role in TCS-induced glycolysis, which was further confirmed by inhibitor tests using specific inhibitors LY294002 and MK2206. In general, TCS can induce oxidative stress, cause oxidative damages and promote glycolysis in HepG2 cells, which was mediated by the PI3K/Akt/FoxO pathway. Keywords: Glycolysis, Molecular mechanism, PI3K/Akt/FoxO pathway |
| first_indexed | 2024-04-12T20:33:06Z |
| format | Article |
| id | doaj.art-a8a79b40faa348bbba998ec72a721205 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-12T20:33:06Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-a8a79b40faa348bbba998ec72a7212052022-12-22T03:17:41ZengElsevierEnvironment International0160-41202020-03-01136PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS)Jing An0Huixin He1Weiwei Yao2Yu Shang3Yun Jiang4Zhiqiang Yu5Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR ChinaInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR ChinaInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR ChinaInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR ChinaShuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Corresponding authors.State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, PR China; Corresponding authors.Triclosan (TCS) has been widely used as an antibacterial agent for the last several decades in personal care products. The toxicological effect of TCS has attracted more and more attention of researchers. The purpose of this study is to evaluate the cytotoxic effects of TCS in HepG2 cells and to elucidate the molecular mechanism focusing on regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) pathway in the glycolytic metabolism. In this study, we evaluated the adverse effect of TCS exposure on cell viability, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP). In addition, the glycolysis process in HepG2 cells exposed to TCS was examined in terms of glucose consumption, lactate production and ATP generation. Furthermore, Affymetrix Human U133 plus 2.0 gene chips and gene function enrichment analysis were conducted to screen differential expression genes (DEGs) and potential signaling pathway. Expressions of the glycolysis-related proteins were measured and quantified with Western Blotting. The results showed that TCS could suppress the cell viability, induce oxidative stress, and cause mitochondrial damage. In addition, TCS exposure promoted the glycolysis process, as manifested by accelerated conversion of glucose to lactate and increased energy release. Western Blotting results confirmed that the expression levels of glycolysis related proteins were significantly elevated. The PI3K/Akt/FoxO pathway was identified to play a pivot role in TCS-induced glycolysis, which was further confirmed by inhibitor tests using specific inhibitors LY294002 and MK2206. In general, TCS can induce oxidative stress, cause oxidative damages and promote glycolysis in HepG2 cells, which was mediated by the PI3K/Akt/FoxO pathway. Keywords: Glycolysis, Molecular mechanism, PI3K/Akt/FoxO pathwayhttp://www.sciencedirect.com/science/article/pii/S0160412019330570 |
| spellingShingle | Jing An Huixin He Weiwei Yao Yu Shang Yun Jiang Zhiqiang Yu PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS) Environment International |
| title | PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS) |
| title_full | PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS) |
| title_fullStr | PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS) |
| title_full_unstemmed | PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS) |
| title_short | PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS) |
| title_sort | pi3k akt foxo pathway mediates glycolytic metabolism in hepg2 cells exposed to triclosan tcs |
| url | http://www.sciencedirect.com/science/article/pii/S0160412019330570 |
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