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Mechanism underlying carbon tetrachloride-inhibited protein synthesis in liver

Author(s): Xiao-Wen Li, Rong Zhu, Bo Li, Mei Zhou, Qing-Jian Sheng, Ye-Peng Yang, Nan-Yin Han, Zai-Quan Li

Journal: World Journal of Gastroenterology
ISSN 1007-9327

Volume: 16;
Issue: 31;
Start page: 3950;
Date: 2010;
Original page

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

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.
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