論文

査読有り
2014年3月

The involvement of endoplasmic reticulum stress in bile acid-induced hepatocellular injury

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
  • Tetsuo Adachi
  • ,
  • Tomoyuki Kaminaga
  • ,
  • Hiroyuki Yasuda
  • ,
  • Tetsuro Kamiya
  • ,
  • Hirokazu Hara

54
2
開始ページ
129
終了ページ
135
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3164/jcbn.13-46
出版者・発行元
JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

Secondary bile acids produced by enteric bacteria accumulate to high levels in the enterohepatic circulation and may contribute to the pathogenesis of hepatocellular injury. Relative hydrophobicity has been suggested to be an important determinant of the biological properties of these compounds, although the mechanism by which bile acids induce pathogenesis is not fully understood. On the other hand, endoplasmic reticulum stress has been shown to be involved in the induction and development of various pathogenic conditions. In this report, we demonstrated that the intensities of cytotoxicity and endoplasmic reticulum stress in HepG2 cells triggered by the bile acids tested were largely dependent on their hydrophobicity. The activation of caspase-3 and DNA fragmentation by treatment with chenodeoxycholic acid showed the contribution of apoptosis to cytotoxicity. Increases in intracellular calcium levels and the generation of reactive oxygen species stimulated by treatment with chenodeoxycholic acid contributed to endoplasmic reticulum stress. Bile acids also induced transforming growth factor-beta, a potent profibrogenic factor, which is known to induce hepatocyte apoptosis and ultimately liver fibrosis. In conclusion, our study demonstrated that bile acids induced endoplasmic reticulum stress, which in turn stimulated apoptosis in HepG2 cells, in a hydrophobicity-dependent manner.

Web of Science ® 被引用回数 : 21

リンク情報
DOI
https://doi.org/10.3164/jcbn.13-46
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24688223
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000334987700011&DestApp=WOS_CPL