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Downregulation of citrin, a mitochondrial AGC, is associated with apoptosis of hepatocytes.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2007 Dec 28; Vol. 364 (4), pp. 937-44. Date of Electronic Publication: 2007 Oct 26. - Publication Year :
- 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.
- Subjects :
- Calcium-Binding Proteins genetics
Caspases metabolism
Cells, Cultured
Citrullinemia genetics
Citrullinemia metabolism
Citrullinemia pathology
Cytochromes c metabolism
Humans
Organic Anion Transporters genetics
RNA, Small Interfering genetics
Amino Acid Transport Systems, Acidic metabolism
Antiporters metabolism
Apoptosis
Calcium-Binding Proteins metabolism
Down-Regulation genetics
Hepatocytes cytology
Hepatocytes metabolism
Mitochondria metabolism
Organic Anion Transporters metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 364
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 18273444
- Full Text :
- https://doi.org/10.1016/j.bbrc.2007.10.105