Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes.
Life Sci
; 87(13-14): 431-8, 2010 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-20807545
ABSTRACT
AIMS:
the effects of bisphenol A (BPA) on NCTC Clone 1469, non-parenchymal hepatocytes, were examined to clarify the molecular basis of BPA-induced liver injury. MAINMETHODS:
we analyzed the expression of C/EBP homologous protein (CHOP) mRNA, Bcl2 mRNA, caspase12, and glucose-regulated protein 78 kDa (GRP78)/Ig heavy chain-binding protein (BiP), to determine whether endoplasmic reticulum (ER) stress was involved in the 100 µM BPA-induced cell death. To examine the features of damaged hepatocytes, we analyzed the morphological changes in BPA-treated NCTC Clone 1469 by transmission electron microscopy. In addition, we analyzed the intracellular reactive oxygen species (ROS) level in BPA-treated NCTC Clone 1469 by the 2', 7'-dichlorofluorescein diacetate (DCFDA) method. KEYFINDINGS:
increases in the expression of CHOP mRNA, caspase-12, and GRP78/BiP in NCTC Clone 1469-treated with 100 µM BPA were detected (CHOP, 1.42 fold; caspase-12, 1.33 fold; GRP78/Bip, 1.36 fold). These observations suggested that BPA induced ER stress-associated apoptosis. A morphological analysis revealed remarkable elongation of the rough ER, supporting the finding of ER stress. Intracellular ROS production was increased in NCTC Clone 1469-treated with BPA, and N-acetyl-l-cysteine (NAC) prevented the cell damage induced by BPA. However, these effects of BPA were not inhibited by estrogen receptor inhibitors.SIGNIFICANCE:
we found that BPA induced ER stress-associated apoptosis in non-parenchymal hepatocytes. The ER stress is due to ROS production and is independent of estrogen receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Apoptose
/
Hepatócitos
/
Retículo Endoplasmático
/
Estrogênios não Esteroides
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article