Yu-Wen Li1, Xiao-Hua Wang, Qin Nin, Xiao-Ping Luo. 1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract
OBJECTIVE: To establish a hepatolenticular degeneration rat model with excessive copper, and investigate the effects of excessive copper deposits in the liver on hepatocyte apoptosis and Bax and Bcl-2 expression. METHODS: Rat model of hepatolenticular degeneration was established by administering forages containing 1g/kg of copper sulfate and drinking water containing 0.185% copper sulfate. Copper level in the liver and serum and alanine aminotransferase (ALT) level in serum were measured using an atomic absorption spectrophotometer. The terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) method was used to detect hepatocyte apoptosis. Bax and Bcl-2 expression was observed by RT-PCR and imunohistochemistry staining. Quantification of positive cells was performed by image analyzer. RESULTS: With more prolonged excessive copper ingestion, copper level in the liver and serum as well as ALT level in serum rose, and more apoptosis cells appeared in the liver. Bax and Bcl-2 expression increased significantly compared with controls fed a normal diet and progressively increased with more prolonged excessive copper ingestion. The progressively increased extent of Bcl-2 expression was lower than that of Bax expression, so the ratio of Bcl-2/Bax decreased with increasing excessive copper ingestion time. CONCLUSIONS: Excessive copper deposits in the liver can induce hepatocyte apoptosis through an up-regulation of Bax expression.
OBJECTIVE: To establish a hepatolenticular degenerationrat model with excessive copper, and investigate the effects of excessive copper deposits in the liver on hepatocyte apoptosis and Bax and Bcl-2 expression. METHODS:Rat model of hepatolenticular degeneration was established by administering forages containing 1g/kg of copper sulfate and drinking water containing 0.185% copper sulfate. Copper level in the liver and serum and alanine aminotransferase (ALT) level in serum were measured using an atomic absorption spectrophotometer. The terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) method was used to detect hepatocyte apoptosis. Bax and Bcl-2 expression was observed by RT-PCR and imunohistochemistry staining. Quantification of positive cells was performed by image analyzer. RESULTS: With more prolonged excessive copper ingestion, copper level in the liver and serum as well as ALT level in serum rose, and more apoptosis cells appeared in the liver. Bax and Bcl-2 expression increased significantly compared with controls fed a normal diet and progressively increased with more prolonged excessive copper ingestion. The progressively increased extent of Bcl-2 expression was lower than that of Bax expression, so the ratio of Bcl-2/Bax decreased with increasing excessive copper ingestion time. CONCLUSIONS:Excessive copper deposits in the liver can induce hepatocyte apoptosis through an up-regulation of Bax expression.
Authors: Pieter Spincemaille; Gursimran Chandhok; Benjamin Newcomb; Jef Verbeek; Kim Vriens; Andree Zibert; Hartmut Schmidt; Yusuf A Hannun; Jos van Pelt; David Cassiman; Bruno P A Cammue; Karin Thevissen Journal: Biochim Biophys Acta Date: 2014-03-13
Authors: Pieter Spincemaille; Gursimran Chandhok; Andree Zibert; Hartmut Schmidt; Jef Verbeek; Patrick Chaltin; Bruno P Cammue; David Cassiman; Karin Thevissen Journal: Microb Cell Date: 2014-10-24