Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes
Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated me...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322012015 |
| _version_ | 1828071638146482176 |
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| author | Chuanhai Li Lidan Jiang Yuan Qi Donghui Zhang Xinya Liu Wenchao Han Wanli Ma Lin Xu Yuan Jin Jiao Luo Kunming Zhao Dianke Yu |
| author_facet | Chuanhai Li Lidan Jiang Yuan Qi Donghui Zhang Xinya Liu Wenchao Han Wanli Ma Lin Xu Yuan Jin Jiao Luo Kunming Zhao Dianke Yu |
| author_sort | Chuanhai Li |
| collection | DOAJ |
| description | Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated metabolomics and proteomics analysis to investigate the altered profiles in metabolite and protein levels in primary human hepatocytes (PHH) exposed to 6:2 Cl-PFESA and PFOS at human exposure relevant concentrations. Our results showed that 6:2 Cl-PFESA exhibited higher perturbation effects on cell viability, metabolome and proteome than PFOS. Integration of metabolomics and proteomics revealed that the alteration of glycerophospholipid metabolism was the critical pathway of 6:2 Cl-PFESA and PFOS-induced lipid metabolism disorder in primary human hepatocytes. Interestingly, 6:2 Cl-PFESA-induced cellular metabolic process disorder was associated with the cellular membrane-bounded signaling pathway, while PFOS was associated with the intracellular transport process. Moreover, the disruption effects of 6:2 Cl-PFESA were also involved in inositol phosphate metabolism and phosphatidylinositol signaling system. Overall, this study provided comprehensive insights into the hepatic lipid toxicity mechanisms of 6:2 Cl-PFESA and PFOS in human primary hepatocytes. |
| first_indexed | 2024-04-11T00:57:02Z |
| format | Article |
| id | doaj.art-dac78adc25c84133aa2d9be820e4a916 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T00:57:02Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-dac78adc25c84133aa2d9be820e4a9162023-01-05T04:30:22ZengElsevierEcotoxicology and Environmental Safety0147-65132023-01-01249114361Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytesChuanhai Li0Lidan Jiang1Yuan Qi2Donghui Zhang3Xinya Liu4Wenchao Han5Wanli Ma6Lin Xu7Yuan Jin8Jiao Luo9Kunming Zhao10Dianke Yu11School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaDepartment of Pediatrics, Qingdao Municipal Hospital, Affiliated to Qingdao University, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, ChinaSchool of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China; Corresponding author.Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated metabolomics and proteomics analysis to investigate the altered profiles in metabolite and protein levels in primary human hepatocytes (PHH) exposed to 6:2 Cl-PFESA and PFOS at human exposure relevant concentrations. Our results showed that 6:2 Cl-PFESA exhibited higher perturbation effects on cell viability, metabolome and proteome than PFOS. Integration of metabolomics and proteomics revealed that the alteration of glycerophospholipid metabolism was the critical pathway of 6:2 Cl-PFESA and PFOS-induced lipid metabolism disorder in primary human hepatocytes. Interestingly, 6:2 Cl-PFESA-induced cellular metabolic process disorder was associated with the cellular membrane-bounded signaling pathway, while PFOS was associated with the intracellular transport process. Moreover, the disruption effects of 6:2 Cl-PFESA were also involved in inositol phosphate metabolism and phosphatidylinositol signaling system. Overall, this study provided comprehensive insights into the hepatic lipid toxicity mechanisms of 6:2 Cl-PFESA and PFOS in human primary hepatocytes.http://www.sciencedirect.com/science/article/pii/S01476513220120156:2 Cl-PFESAPFOSProteomicsMetabolomicsPrimary human hepatocytes |
| spellingShingle | Chuanhai Li Lidan Jiang Yuan Qi Donghui Zhang Xinya Liu Wenchao Han Wanli Ma Lin Xu Yuan Jin Jiao Luo Kunming Zhao Dianke Yu Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes Ecotoxicology and Environmental Safety 6:2 Cl-PFESA PFOS Proteomics Metabolomics Primary human hepatocytes |
| title | Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes |
| title_full | Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes |
| title_fullStr | Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes |
| title_full_unstemmed | Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes |
| title_short | Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes |
| title_sort | integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate pfos and 6 2 chlorinated polyfluoroalkyl ether sulfonic acid 6 2 cl pfesa in primary human hepatocytes |
| topic | 6:2 Cl-PFESA PFOS Proteomics Metabolomics Primary human hepatocytes |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322012015 |
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