Super-induced gene expression of the N-methyl-D-aspartate receptor 2C subunit in chemical-induced hypertrophic liver in rats.
To identify gene expression that can be closely involved in chemical-induced hepatocellular hypertrophy, the hepatic gene expression profile was assessed by cDNA microarray analysis in male F344 rats fed for 3 days, 4 weeks, and 13 weeks a diet containing a hepatocellular hypertrophy inducer, either phenobarbital (500 ppm), clofibrate (2,500 ppm), or piperonyl butoxide (20,000 ppm). The results showed that, in all treatment groups, the increased expressional rate of the Grin2c gene, which encodes the N-methyl-D-aspartate receptor 2C subunit (NR2C), was the highest among those of all the genes tested, as compared with the corresponding gene expression in rats fed a normal diet. Moreover, real-time RT-PCR analysis showed that the expression levels of the Grin2c gene in rats fed with each chemical clearly increased in a chemical treatment period-dependent fashion, and that the increased rate was closely correlated with the grade of hypertrophy of hepatocytes rather than with the increased rate in liver weight. These results suggest the possibility that chemical-induced NR2C expression relates to the development of hepatocellular hypertrophy.
Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. nemoto@u-shizuoka-ken.ac.jp
Kiyomitsu
K
Nemoto
Takahiro
T
Tanaka
Ayaka
A
Ikeda
Sei
S
Ito
Masanori
M
Mizukami
Tokihiro
T
Hikida
Toshie
T
Gamou
Wataru
W
Habano
Shogo
S
Ozawa
Kaoru
K
Inoue
Midori
M
Yoshida
Akiyoshi
A
Nishikawa
Masakuni
M
Degawa
D000818:Animals; D002994:Clofibrate / Q000633:toxicity; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D006529:Hepatomegaly / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000633:toxicity; D010882:Piperonyl Butoxide / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C432823:NR2C NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D002994:Clofibrate; D010882:Piperonyl Butoxide; D010634:Phenobarbital