Nitro-Oxidative Stress and Mitochondrial Dysfunction in Human Cell Lines Exposed to the Environmental Contaminants PFOA and BPA.
emerging contaminants
endocrine disruptors
mitochondrial dysfunction
nitric oxide signaling
nitro-oxidative stress
Journal
Frontiers in bioscience (Landmark edition)
ISSN: 2768-6698
Titre abrégé: Front Biosci (Landmark Ed)
Pays: Singapore
ID NLM: 101612996
Informations de publication
Date de publication:
27 10 2022
27 10 2022
Historique:
received:
26
07
2022
revised:
13
09
2022
accepted:
10
10
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
9
11
2022
Statut:
ppublish
Résumé
Bisphenol A (BPA) and perfluorooctanoic acid (PFOA) are synthetic compounds widely utilized in industrial activities devoted to the production of daily life plastic, metal products, and packaging from which they are able to migrate to food and water. Due to their persistence in the environment, living organisms are chronically exposed to these pollutants. BPA and PFOA have adverse effects on tissues and organs. The aim of this study was to identify the molecular targets and biochemical mechanisms involved in their toxicity. HepG2 and HaCaT cells were treated with BPA or PFOA, and the trypan blue exclusion test and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay were performed to define the conditions for subsequent investigations. We conducted quantitative PCR and western blot analysis to evaluate the expression of proteins involved in nitric oxide (NO) signaling. Cell-based assays were carried out to evaluate reactive oxygen species (ROS) production, nitrite/nitrate (NOx) accumulation, 3-nitrotyrosine (3-NT) formation, and mitochondrial membrane potential (MMP) determination in treated cells. HepG2 and HaCaT cells incubated for 24 h with subtoxic concentrations of BPA or PFOA (50 and 10 μM, respectively) exhibited altered mRNA and protein expression levels of NO synthase isoforms, manganese superoxide dismutase, and cytochrome c. Treatment with PFOA led to activation of inducible NO synthase (NOS), a marker of nitrosative stress, accompanied by the increased production of ROS, NOx, and 3-NT and alterations of the MMP compared to controls. The results of this study indicate the major involvement of the NO signaling axis in the persistent alteration of cell redox homeostasis and mitochondrial dysfunction induced by BPA and PFOA, highlighting the specific role of PFOA in NOS regulation and induction of nitro-oxidative stress.
Sections du résumé
BACKGROUND
Bisphenol A (BPA) and perfluorooctanoic acid (PFOA) are synthetic compounds widely utilized in industrial activities devoted to the production of daily life plastic, metal products, and packaging from which they are able to migrate to food and water. Due to their persistence in the environment, living organisms are chronically exposed to these pollutants. BPA and PFOA have adverse effects on tissues and organs. The aim of this study was to identify the molecular targets and biochemical mechanisms involved in their toxicity.
METHODS
HepG2 and HaCaT cells were treated with BPA or PFOA, and the trypan blue exclusion test and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay were performed to define the conditions for subsequent investigations. We conducted quantitative PCR and western blot analysis to evaluate the expression of proteins involved in nitric oxide (NO) signaling. Cell-based assays were carried out to evaluate reactive oxygen species (ROS) production, nitrite/nitrate (NOx) accumulation, 3-nitrotyrosine (3-NT) formation, and mitochondrial membrane potential (MMP) determination in treated cells.
RESULTS
HepG2 and HaCaT cells incubated for 24 h with subtoxic concentrations of BPA or PFOA (50 and 10 μM, respectively) exhibited altered mRNA and protein expression levels of NO synthase isoforms, manganese superoxide dismutase, and cytochrome c. Treatment with PFOA led to activation of inducible NO synthase (NOS), a marker of nitrosative stress, accompanied by the increased production of ROS, NOx, and 3-NT and alterations of the MMP compared to controls.
CONCLUSIONS
The results of this study indicate the major involvement of the NO signaling axis in the persistent alteration of cell redox homeostasis and mitochondrial dysfunction induced by BPA and PFOA, highlighting the specific role of PFOA in NOS regulation and induction of nitro-oxidative stress.
Identifiants
pubmed: 36336871
pii: S2768-6701(22)00661-X
doi: 10.31083/j.fbl2710292
doi:
Substances chimiques
perfluorooctanoic acid
947VD76D3L
bisphenol A
MLT3645I99
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
292Informations de copyright
© 2022 The Author(s). Published by IMR Press.
Déclaration de conflit d'intérêts
Luciano Saso is serving as one of the Guest Editors of the special issue “Modulation of oxidative stress: Biochemcal and pharmacological aspects”, in this journal. We declare that Luciano Saso had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process of this article was delegated to Josef Jampílek.