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Augmenter of liver regeneration: An important intracellular survival factor for hepatocytes

Thirunavukkarasu, C and Wang, LF and Harvey, SAK and Watkins, SC and Chaillet, JR and Prelich, J and Starzl, TE and Gandhi, CR (2008) Augmenter of liver regeneration: An important intracellular survival factor for hepatocytes. Journal of Hepatology, 48 (4). 578 - 588. ISSN 0168-8278

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Abstract

Background/Aims: Augmenter of liver regeneration (ALR), a protein synthesized and stored in hepatocytes, is associated with mitochondria, and possesses sulfhydryl oxidase and cytochrome c reductase activities. We sought to determine the effects of ALR depletion in hepatocytes by antisense oligonucleotide transfection. Methods: Rat hepatocytes in primary culture were transfected with antisense oligonucleotide for ALR mRNA (ALR-AS) or scrambled oligonucleotide. Various analyses were performed at times up to 24 h after transfection. Results: Treatment with ALR-AS caused a decrease in ALR mRNA, cellular depletion of ALR protein primarily from mitochondria, and decreased viability. Flow cytometric analysis of ALR-AS-transfected hepatocytes stained with annexin-V cy3 and 7-aminoactinomycin D revealed apoptosis as the predominant cause of death up to 6 h; incubation beyond this time resulted in necrosis in addition to apoptosis. ALR-AS-transfection caused release of mitochondrial cytochrome c, activation of caspase-3, profound reduction in the ATP content, and cellular release of LDH. Inhibition of caspase-3 inhibited the early phase of ALR-AS-induced death but not the late phase that included ALR and LDH release. Conclusions: These results suggest that ALR is critically important for the survival of hepatocytes by its association with mitochondria and regulation of ATP synthesis. © 2008 European Association for the Study of the Liver.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Thirunavukkarasu, C
Wang, LF
Harvey, SAK
Watkins, SC
Chaillet, JR
Prelich, J
Starzl, TEtes11@pitt.eduTES11
Gandhi, CR
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 April 2008
Date Type: Publication
Journal or Publication Title: Journal of Hepatology
Volume: 48
Number: 4
Page Range: 578 - 588
DOI or Unique Handle: 10.1016/j.jhep.2007.12.010
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0168-8278
Other ID: uls-drl:31735062121557, Starzl CV No. 2246
Date Deposited: 08 Apr 2010 17:38
Last Modified: 12 Oct 2017 08:56
URI: http://d-scholarship.pitt.edu/id/eprint/5632

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