Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins
Dichlorodiphenyldichloroethylene (DDE), the primary persistent metabolite of dichlorodiphenyltrichloroethane (DDT), has toxic effects on cells, but its dose-dependent impact on mitochondrial proteins involved in mitochondrial fusion and fission processes associated with cell viability impairment has...
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MDPI AG
2021-10-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/9/11/270 |
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| author | Mario Alberto Burgos Aceves Vincenzo Migliaccio Marilena Lepretti Gaetana Paolella Ilaria Di Gregorio Serena Penna Caterina Faggio Lillà Lionetti |
| author_facet | Mario Alberto Burgos Aceves Vincenzo Migliaccio Marilena Lepretti Gaetana Paolella Ilaria Di Gregorio Serena Penna Caterina Faggio Lillà Lionetti |
| author_sort | Mario Alberto Burgos Aceves |
| collection | DOAJ |
| description | Dichlorodiphenyldichloroethylene (DDE), the primary persistent metabolite of dichlorodiphenyltrichloroethane (DDT), has toxic effects on cells, but its dose-dependent impact on mitochondrial proteins involved in mitochondrial fusion and fission processes associated with cell viability impairment has not yet been analysed. Mitochondrial fusion and fission processes are critical to maintaining the mitochondrial network and allowing the cell to respond to external stressors such as environmental pollutants. Fusion processes are associated with optimizing mitochondrial function, whereas fission processes are associated with removing damaged mitochondria. We assessed the effects of different DDE doses, ranging between 0.5 and 100 µM, on cell viability and mitochondrial fusion/fission proteins in an in vitro hepatic cell model (human hepatocarcinomatous cells, HepG2); the DDE induced a decrease in cell viability in a dose-dependent manner, and its effect was enhanced in conditions of coincubation with dietary fatty acids. Fusion protein markers exhibited an inverted U-shape dose-response curve, showing the highest content in the 2.5–25 μM DDE dose range. The fission protein marker was found to increase significantly, leading to an increased fission/fusion ratio with high DDE doses. The low DDE doses elicited cell adaption by stimulating mitochondrial dynamics machinery, whereas high DDE doses induced cell viability loss associated with mitochondrial dynamics to shift toward fission. Present results are helpful to clarify the mechanisms underlying the cell fate towards survival or death in response to increasing doses of environmental pollutants. |
| first_indexed | 2024-03-10T05:01:44Z |
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| id | doaj.art-fe3a60d5e0f2429cac4687166c4e9349 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-10T05:01:44Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-fe3a60d5e0f2429cac4687166c4e93492023-11-23T01:47:28ZengMDPI AGToxics2305-63042021-10-0191127010.3390/toxics9110270Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission ProteinsMario Alberto Burgos Aceves0Vincenzo Migliaccio1Marilena Lepretti2Gaetana Paolella3Ilaria Di Gregorio4Serena Penna5Caterina Faggio6Lillà Lionetti7Department of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale F. Stagno d’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDichlorodiphenyldichloroethylene (DDE), the primary persistent metabolite of dichlorodiphenyltrichloroethane (DDT), has toxic effects on cells, but its dose-dependent impact on mitochondrial proteins involved in mitochondrial fusion and fission processes associated with cell viability impairment has not yet been analysed. Mitochondrial fusion and fission processes are critical to maintaining the mitochondrial network and allowing the cell to respond to external stressors such as environmental pollutants. Fusion processes are associated with optimizing mitochondrial function, whereas fission processes are associated with removing damaged mitochondria. We assessed the effects of different DDE doses, ranging between 0.5 and 100 µM, on cell viability and mitochondrial fusion/fission proteins in an in vitro hepatic cell model (human hepatocarcinomatous cells, HepG2); the DDE induced a decrease in cell viability in a dose-dependent manner, and its effect was enhanced in conditions of coincubation with dietary fatty acids. Fusion protein markers exhibited an inverted U-shape dose-response curve, showing the highest content in the 2.5–25 μM DDE dose range. The fission protein marker was found to increase significantly, leading to an increased fission/fusion ratio with high DDE doses. The low DDE doses elicited cell adaption by stimulating mitochondrial dynamics machinery, whereas high DDE doses induced cell viability loss associated with mitochondrial dynamics to shift toward fission. Present results are helpful to clarify the mechanisms underlying the cell fate towards survival or death in response to increasing doses of environmental pollutants.https://www.mdpi.com/2305-6304/9/11/270environmental pollutantshepatocytesmitochondriaMfn2DRP1SOD |
| spellingShingle | Mario Alberto Burgos Aceves Vincenzo Migliaccio Marilena Lepretti Gaetana Paolella Ilaria Di Gregorio Serena Penna Caterina Faggio Lillà Lionetti Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins Toxics environmental pollutants hepatocytes mitochondria Mfn2 DRP1 SOD |
| title | Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins |
| title_full | Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins |
| title_fullStr | Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins |
| title_full_unstemmed | Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins |
| title_short | Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins |
| title_sort | dose dependent response to the environmental pollutant dichlorodipheniletylhene dde in hepg2 cells focus on cell viability and mitochondrial fusion fission proteins |
| topic | environmental pollutants hepatocytes mitochondria Mfn2 DRP1 SOD |
| url | https://www.mdpi.com/2305-6304/9/11/270 |
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