| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Research Abstract |
This study was conducted to evaluate the role of endoplasmic reticulum (ER) stress in acetaminophen-induced liver injury in mice. We demonstrated the hepatic Xbp1 mRNA splicing induction by APAP injection using ERAI (ER stress activated indicator) transgenic mice. In addition, we proved that C/EBP homologous protein, an ER stress related-transcriptional factor, null mice were protected from APAP induced hepatotoxicity compared with wild-type mice. Furthermore, we also found that 4-phenylbutyric acid (4-PBA), an ER stress suppressor, significantly attenuated the APAP-induced liver injury in mice. These results indicate that ER stress plays important role in the development of APAP hepatotoxicity in mice, and suggest that ER stress suppression is a promising therapeutic strategy against APAP-induced liver injury.
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