Early transcriptional deregulation of hepatic mitochondrial biogenesis and its consequent effects on murine cholestatic liver injury

Mao Meng Tiao, Tsu Kung Lin, Cha Wei Liou, Pei Wen Wang, Jin Bor Chen, Fang Ying Kuo, Chao Cheng Huang, Yao Min Chou, Jiin Haur Chuang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

35 Scopus citations

Abstract

Mitochondria are known to be involved in cholestatic liver injury, but the damage and biogenesis of mitochondria in response to the early stage of cholestasis is unknown. A rat model of cholestasis was established by bile duct ligation (BDL), with simultaneous creation of the sham group receiving laparotomy without BDL. A significant decrease of liver peroxisome proliferators-activated receptor γ coactivator-1α, mitochondrial transcriptional factor A (Tfam) and glutathione peroxidase (GPx) mRNA and Tfam protein from 6 to 72 h after BDL was found, which was associated with significant decrease of the glutathione, GPx and catalase activity at 72 h. At 72 h after BDL, mitochondrial DNA copy number reached the lowest level, while caspase 9 and 3 activity, but not caspase 8, Bax, Bcl2, Fas L and Fas-Fas L complex, were upregulated significantly in the liver homogenates of BDL rats. The apoptotic liver cells appeared in large amounts in the rat liver by 72 h after BDL. Our results indicate that transcriptional regulation of the mitochondrial biogenesis is impaired within a few hours after complete bile duct obstruction, resulting in later mitochondrial dysfunction and consequent cholestatic liver injury via the intrinsic apoptosis pathway.

Original languageEnglish
Pages (from-to)890-899
Number of pages10
JournalApoptosis
Volume14
Issue number7
DOIs
StatePublished - 07 2009

Keywords

  • Apoptosis
  • Cholestasis
  • Mitochondria
  • PGC-1
  • Tfam

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