MISC

2007年12月

Downregulation of citrin, a mitochondrial AGC, is associated with apoptosis of hepatocytes

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Shigeki Sawada
  • ,
  • Takao Kinjo
  • ,
  • Shoko Makishi
  • ,
  • Mariko Tomita
  • ,
  • Akira Arasaki
  • ,
  • Kunitoshi Iseki
  • ,
  • Hisami Watanabe
  • ,
  • Keiko Kobayashi
  • ,
  • Hajime Sunakawa
  • ,
  • Teruo Iwamasa
  • ,
  • Naoki Mori

364
4
開始ページ
937
終了ページ
944
記述言語
英語
掲載種別
DOI
10.1016/j.bbrc.2007.10.105
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

Citrin is a mitochondrial aspartate-glutamate carrier primarily expressed in liver. Adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin, and patients with this condition do not express citrin. We found apoptotic hepatocytes in one such patient. This finding prompted us to investigate the role of citrin in hepatocyte survival. Knockdown of citrin by a vector-based short-hairpin RNA technique reduced cell viability and induced apoptosis of a hepatocellular carcinoma cell line, Hep3B cells. Caspase-3/7 and caspase-9 were activated, and PARP was cleaved. Citrin knockdown also increased the expression of Bax and Bak, and reduced expression of Bcl-xL and Bcl-2. These alterations resulted in the release of cytochrome c from the mitochondria. Our results indicated that citrin downregulation induces apoptosis of hepatocytes through the mitochondrial death pathway, highlighting the importance of citrin in survival of hepatocytes and maintenance of liver function. (C) 2007 Elsevier Inc. All rights reserved.


リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2007.10.105
CiNii Articles
http://ci.nii.ac.jp/naid/120001372496
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000251358500037&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.bbrc.2007.10.105
  • ISSN : 0006-291X
  • CiNii Articles ID : 120001372496
  • Web of Science ID : WOS:000251358500037

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