Mechanism underlying carbon tetrachloride-inhibited protein synthesis in liver.
OBJECTIVE
To study the mechanism underlying carbon tetrachloride (CCl(4)) -induced alterations of protein synthesis in liver.


METHODS
Male Sprague-Dawley rats were given CCl(4) (1 mL/100 g body weight) and (3)H-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 CCl(4) treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl(4) 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 CCl(4). In addition, CCl(4) 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 CCl(4)-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)(+) mRNA molecules in morphological hybridization research.


CONCLUSIONS
Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.
Li
Xiao-Wen
XW
Department of Radiation Medicine, Peking University Health Science Center, Beijing, China.
Zhu
Rong
R
Li
Bo
B
Zhou
Mei
M
Sheng
Qing-Jian
QJ
Yang
Ye-Peng
YP
Han
Nan-Yin
NY
Li
Zai-Quan
ZQ
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005609:Free Radicals / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D043583:Nucleoside-Triphosphatase / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D012333:RNA, Messenger; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D043583:Nucleoside-Triphosphatase