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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Autores principales:	Mario Alberto Burgos Aceves, Vincenzo Migliaccio, Marilena Lepretti, Gaetana Paolella, Ilaria Di Gregorio, Serena Penna, Caterina Faggio, Lillà Lionetti
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	environmental pollutants hepatocytes mitochondria Mfn2 DRP1 SOD Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/fe3a60d5e0f2429cac4687166c4e9349
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spelling	oai:doaj.org-article:fe3a60d5e0f2429cac4687166c4e93492021-11-25T19:07:57ZDose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins10.3390/toxics91102702305-6304https://doaj.org/article/fe3a60d5e0f2429cac4687166c4e93492021-10-01T00:00:00Zhttps://www.mdpi.com/2305-6304/9/11/270https://doaj.org/toc/2305-6304Dichlorodiphenyldichloroethylene (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.Mario Alberto Burgos AcevesVincenzo MigliaccioMarilena LeprettiGaetana PaolellaIlaria Di GregorioSerena PennaCaterina FaggioLillà LionettiMDPI AGarticleenvironmental pollutantshepatocytesmitochondriaMfn2DRP1SODChemical technologyTP1-1185ENToxics, Vol 9, Iss 270, p 270 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	environmental pollutants hepatocytes mitochondria Mfn2 DRP1 SOD Chemical technology TP1-1185
spellingShingle	environmental pollutants hepatocytes mitochondria Mfn2 DRP1 SOD Chemical technology TP1-1185 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
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.
format	article
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
title	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_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_sort	dose-dependent response to the environmental pollutant dichlorodipheniletylhene (dde) in hepg2 cells: focus on cell viability and mitochondrial fusion/fission proteins
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fe3a60d5e0f2429cac4687166c4e9349
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Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins

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