Super-induced gene expression of the N-methyl-D-aspartate receptor 2C subunit in chemical-induced hypertrophic liver in rats

  • Nemoto Kiyomitsu
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
  • Tanaka Takahiro
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
  • Ikeda Ayaka
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
  • Ito Sei
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
  • Mizukami Masanori
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
  • Hikida Tokihiro
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
  • Gamou Toshie
    Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
  • Habano Wataru
    Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
  • Ozawa Shogo
    Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
  • Inoue Kaoru
    Division of Pathology, National Institute of Health Sciences
  • Yoshida Midori
    Division of Pathology, National Institute of Health Sciences
  • Nishikawa Akiyoshi
    Division of Pathology, National Institute of Health Sciences
  • Degawa Masakuni
    Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka Global Center of Excellence (COE) Program, University of Shizuoka

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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.

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