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
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-Vcy3 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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Thirunavukkarasu, C | | | | Wang, LF | | | | Harvey, SAK | | | | Watkins, SC | | | | Chaillet, JR | | | | Prelich, J | | | | Starzl, TE | tes11@pitt.edu | TES11 | | Gandhi, CR | | | |
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Centers: |
Other Centers, Institutes, Offices, 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: |
22 Jun 2021 14:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/5632 |
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