Skip Navigation



Human Molecular Genetics Advance Access published online on September 2, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi333
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
14/20/3019    most recent
ddi333v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lu, S.
Right arrow Articles by Wang, Y. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lu, S.
Right arrow Articles by Wang, Y. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved
Received July 14, 2005
Revised August 26, 2005
Accepted August 26, 2005

Article

Impaired hepatocyte survival and liver regeneration in Atm-deficient mice

Shu Lu 1, Kate C. Shen 1, Yaolin Wang 2, S. C. Brooks 3, and Y. Alan Wang 1*

1 Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, 110 E. Warren Ave., Detroit, MI 48201
2 Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, NJ 07033
3 Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, 110 E. Warren Ave., Detroit, MI 48201; Dept. of Biochemistry & Molecular Biology, School of Medicine, Wayne State University, 110 E. Warren Ave., Detroit, MI 48201

* To whom correspondence should be addressed.
Y. Alan Wang, E-mail: wangya{at}karmanos.org


  Abstract

Atm is a stress-induced DNA damage checkpoint protein kinase with multiple roles in cell cycle progression. Recent evidence indicates that Atm also plays a role in stem cell maintenance and self-renewal. It is not known whether Atm has a role during tissue regeneration. Using liver regeneration as a model system, we examined the role of Atm in this process. Here we show that the expression levels of Atm protein were gradually increased during liver regeneration and this was correlated with the onset of DNA replication. The induction of Stat3 and JNK signaling, which are essential processes in normal regeneration response, was attenuated during the early phases of liver regeneration in Atm deficient mice. P53 was transiently phosphorylated at serine 23 during liver regeneration in an Atm-dependent manner. In addition, we found that cyclin A induction was delayed and p21 was overexpressed, both of these processes were correlated with reduced and delayed DNA replication in Atm-/- mice during liver regeneration. Finally, we show that increased apoptosis was observed in Atm-/- mice in response to partial hepatectomy, indicating that Atm is required for the survival of hepatocytes. Collectively, these data indicate that liver regeneration is impaired in Atm-deficient mice. Given that liver is the first line of defense against environmental toxins, the elucidation of the function of Atm and Atm-mediated signaling pathways in liver metabolism and in response to environmental toxins is of fundamental interest.

Keywords: Ataxia-Telangiectasia; ATM; liver regeneration; hepatocyte survival; p53; Stat3; apoptosis.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.