Your browser doesn't support javascript.
loading
Lipopolysaccharide stimulates endogenous ß-glucuronidase via PKC/NF-κB/c-myc signaling cascade: a possible factor in hepatolithiasis formation.
Yao, Dianbo; Dong, Qianze; Tian, Yu; Dai, Chaoliu; Wu, Shuodong.
Afiliação
  • Yao D; Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
  • Dong Q; Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.
  • Tian Y; Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
  • Dai C; Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
  • Wu S; Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China. wushuodong1949@163.com.
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.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Transdução de Sinais / Lipopolissacarídeos / Colestase Intra-Hepática / NF-kappa B / Proteínas Proto-Oncogênicas c-myc / Glucuronidase Limite: Female / Humans / Male Idioma: En Revista: Mol Cell Biochem Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Transdução de Sinais / Lipopolissacarídeos / Colestase Intra-Hepática / NF-kappa B / Proteínas Proto-Oncogênicas c-myc / Glucuronidase Limite: Female / Humans / Male Idioma: En Revista: Mol Cell Biochem Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China