2016年5月
Tryptophan protects hepatocytes against reactive oxygen species-dependent cell death via multiple pathways including Nrf2-dependent gene induction
AMINO ACIDS
- ,
- 巻
- 48
- 号
- 5
- 開始ページ
- 1263
- 終了ページ
- 1274
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s00726-016-2175-6
- 出版者・発行元
- SPRINGER WIEN
Hepatocyte apoptosis plays a key role in the pathogenesis of immune-mediated hepatitis. However, the detailed mechanisms of apoptosis signaling are still unclear and effective therapeutic drugs for hepatitis have been explored. Here, we show that tryptophan (Trp) suppressed IFN-gamma-mediated hepatic apoptosis in vitro. Trp inhibited the downstream apoptotic events of mitochondria disruption, such as cell death and caspase-3 activation, while it did not influence upstream signaling including STAT1 activation and IRF1 expression. Trp suppressed reactive oxygen species (ROS) generation at the mitochondria. IFN-gamma induced ROS in mitochondria by inhibiting complex I and III, but not II. This ROS generation by IFN-gamma required de novo protein synthesis. Trp showed relatively weak direct scavenging activity but antagonized IFN-gamma against the suppression of complex I. In addition, Trp increased the expression of the Nrf2-dependent antioxidant genes NQO1, HO-1 and GCS in hepatocytes both in vitro and in vivo. Finally, the administration of Trp in an acetaminophen-induced ROS-dependent hepatitis model suppressed the liver injury in vivo. Thus, Trp protects hepatocytes from ROS-dependent cell injury via multiple pathways. This study suggests Trp as a therapeutic antioxidant drug for hepatitis and a regulator for Nrf2-dependent genes.
- リンク情報
- ID情報
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- DOI : 10.1007/s00726-016-2175-6
- ISSN : 0939-4451
- eISSN : 1438-2199
- Web of Science ID : WOS:000374375300013