Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Aug 21, 2010; 16(31): 3950-3956
Published online Aug 21, 2010. doi: 10.3748/wjg.v16.i31.3950
Mechanism underlying carbon tetrachloride-inhibited protein synthesis in liver
Xiao-Wen Li, Rong Zhu, Bo Li, Mei Zhou, Qing-Jian Sheng, Ye-Peng Yang, Nan-Yin Han, Zai-Quan Li
Xiao-Wen Li, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China
Rong Zhu, National Institute of Drug Dependence, Peking University Health Science Center, Beijing 100191, China
Bo Li, Mei Zhou, Qing-Jian Sheng, Ye-Peng Yang, Zai-Quan Li, Department of Radiation Medicine, Peking University Health Science Center, Beijing 100191, China
Nan-Yin Han, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
Author contributions: Li ZQ and Han NY designed the study; Li XW, Zhu R and Li B performed the experiments; Zhou M, Sheng QJ and Yang YP assisted some parts of experiments; Li ZQ and Li XW wrote the manuscript.
Supported by The National Natural Science Foundation of China, No. 30470846
Correspondence to: Dr. Zai-Quan Li, Department of Radiation Medicine, Peking University Health Science Center, Beijing100191, China. lizaiquan@bjmu.edu.cn
Telephone: +86-10-82801450 Fax: +86-10-82801450
Received: May 5, 2010
Revised: June 17, 2010
Accepted: June 24, 2010
Published online: August 21, 2010
Abstract

AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver.

METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3’-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl4 were assayed by a double-reciprocal plot.

RESULTS: The protein synthesis was inhibited while the MDA level was significantly increased in liver of rats treated with CCl4. In addition, CCl4 decreased the NTPase binding capacity of nuclear envelope (Km value) in cultured HepG2 cells. Moreover, in vitro ferrous radicals from Fenton’s system suppressed the NTPase activity of liver nuclear envelope in a dose-dependent manner. Down-regulation of the nuclear envelope NTPase activity indicated a lower energy provision for nucleocytoplasmic transport of mRNA molecules, an evidence in CCl4-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)+ mRNA molecules in morphological hybridization research.

CONCLUSION: Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.

Keywords: Carbon tetrachloride, Nuclear envelope nucleotide triphosphatase, Nucleocytoplasmic transport inhibition, Hydroxyl radical