Suppression of apoptotic signaling in rat hepatocytes by non-dioxin-like polychlorinated biphenyls depends on the receptors CAR and PXR.
Toxicology
; 464: 153023, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34743025
ABSTRACT
Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) represent a sub-group of persistent organic pollutants found in food, environmental samples and human and animal tissues. Promotion of pre-neoplastic lesions in rodent liver has been suggested as an indicator for a possible increased risk of liver cancer in humans exposed to NDL-PCBs. In rodent hepatocytes, suppression of DNA damage-triggered apoptosis is a typical mode of action of liver tumor promoters. Here, we report that NDL-PCBs suppress apoptosis in rat hepatocytes treated in culture with an apoptogenic dose of UV light. Suppression became less pronounced when the constitutive androstane receptor (CAR) and/or the pregnane-X-receptor (PXR) where knocked-out using siRNAs, while knocking-out both receptors led to a full reconstitution of apoptosis. In contrast, suppression of apoptosis by the CAR or PXR activators phenobarbital or dexamethasone were CAR- or PXR-specific. Induction and suppression of apoptosis were paralleled by changes in caspase 3/7, 8 and 9 activities. Our findings indicate that NDL-PCBs can suppress UV-induced apoptosis in rat hepatocytes by activating CAR and PXR. It needs further investigation if these mechanisms of action are also of relevance for human liver.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Bifenilos Policlorados
/
Hepatócitos
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Receptor de Pregnano X
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Receptor Constitutivo de Androstano
Limite:
Animals
Idioma:
En
Revista:
Toxicology
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha