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Title :Downregulation of citrin, a mitochondrial aspartate glutamate carrier, is associated with apoptosis of hepatocytes
Authors :Sawada, Shigeki
Kinjo, Takao
Makishi, Shoko
Tomita, Mariko
Arasaki, Akira
Iseki, Kunitoshi
Watanabe, Hisami
Kobayashi, Keiko
Sunakawa, Hajime
Iwamasa, Teruo
Mori, Naoki
Issue Date :28-Dec-2007
Abstract :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.
URL :http://www.sciencedirect.com/science/journal/0006291X
Type Local :雑誌掲載論文
ISSN :0006-291X
Publisher :Elsevier
URI :http://hdl.handle.net/20.500.12000/2807
Citation :Biochemical and Biophysical Research Communications Vol.364 no.4 p.937 -944
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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