Molecular Mechanisms of Perfluorooctanoate-Induced Hepatocyte Apoptosis in Mice Using Proteomic Techniques.
Environ Sci Technol
; 51(19): 11380-11389, 2017 Oct 03.
Article
en En
| MEDLINE
| ID: mdl-28885018
ABSTRACT
The stability of perfluorooctanoate (PFOA) coupled with its wide use cause serious concerns regarding its potential risk to human health. The molecular mechanisms of PFOA-induced hepatotoxicity relevant to human health was investigated using both in vivo (mouse model) and in vitro (human hepatocyte cells, HL-7702) techniques. Both male and female Balb/c mice were administered PFOA at 0.05, 0.5, or 2.5 mg/kg-d for 28-d, with serum PFOA concentrations after exposure being found at environmentally relevant levels. Liver samples were examined for histology and proteomic change using iTRAQ and Western Blotting, showing dose-dependent hepatocyte apoptosis and peroxisome proliferation. At high doses, genotoxicity resulting from ROS hypergeneration was due to suppression of Complex I subunits in the electron transport chain and activation of PPARα in both genders. However, at 0.05 mg/kg-d, Complex I suppression occurred only in females, making them more sensitive to PFOA-induced apoptosis. In vitro assays using HL-7702 cells confirmed that apoptosis was also induced through a similar mechanism. The dose/gender-dependent toxicity mechanisms help to explain some epidemiological phenomena, i.e., liver cancer is not often associated with PFOA exposure in professional workers. Our results demonstrated that a proteomic approach is a robust tool to explore molecular mechanisms of toxic chemicals at environmentally relevant levels.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Caprilatos
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Apoptosis
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Proteómica
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Contaminantes Ambientales
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Fluorocarburos
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Environ Sci Technol
Año:
2017
Tipo del documento:
Article
País de afiliación:
China