Lipopolysaccharide stimulates endogenous ß-glucuronidase via PKC/NF-κB/c-myc signaling cascade: a possible factor in hepatolithiasis formation.
Mol Cell Biochem
; 444(1-2): 93-102, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-29188532
ABSTRACT
Hepatolithiasis is commonly encountered in Southeastern and Eastern Asian countries, but the pathogenesis mechanism of stone formation is still not well understood. Now, the role of endogenous ß-glucuronidase in pigment stones formation is being gradually recognized. In this study, the mechanism of increased expression and secretion of endogenous ß-glucuronidase during hepatolithiasis formation was investigated. We assessed the endogenous ß-glucuronidase, c-myc, p-p65, and p-PKC expression in liver specimens with hepatolithiasis by immunohistochemical staining, and found that compared with that in normal liver samples, the expression of endogenous ß-glucuronidase, c-myc, p-p65, and p-PKC in liver specimens with hepatolithiasis significantly increased, and their expressions were positively correlated with each other. Lipopolysaccharide (LPS) induced increased expression of endogenous ß-glucuronidase and c-myc in hepatocytes and intrahepatic biliary epithelial cells in a dose- and time-dependent manner, and endogenous ß-glucuronidase secretion increased, correspondingly. C-myc siRNA transfection effectively inhibited the LPS-induced expression of endogenous ß-glucuronidase. Furthermore, NF-κB inhibitor pyrrolidine dithiocarbamate or PKC inhibitor chelerythrine could effectively inhibit the LPS-induced expression of c-myc and endogenous ß-glucuronidase, and the expression of p-p65 was also partly inhibited by chelerythrine. Our clinical observations and experimental data indicate that LPS could induce the increased expression and secretion of endogenous ß-glucuronidase via a signaling cascade of PKC/NF-κB/c-myc in hepatocytes and intrahepatic biliary epithelial cells, and endogenous ß-glucuronidase might play a possible role in the formation of hepatolithiasis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
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Transdução de Sinais
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Lipopolissacarídeos
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Colestase Intra-Hepática
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NF-kappa B
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Proteínas Proto-Oncogênicas c-myc
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Glucuronidase
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China