Skip Navigation



Carcinogenesis Advance Access published online on April 7, 2005
Carcinogenesis, doi:10.1093/carcin/bgi083
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/8/1335    most recent
bgi083v1
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 Liu, Y.
Right arrow Articles by Phang, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, Y.
Right arrow Articles by Phang, J. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2005
Received September 28, 2004
Revised March 25, 2005
Accepted March 25, 2005

CANCER BIOLOGY

MnSOD inhibits proline oxidase-induced apoptosis in colorectal cancer cells

Yongmin Liu 1, Gregory L. Borchert 2, Steven P. Donald 1, Arkadiusz Surazynski 1, Chien-An Hu 3, Christine J. Weydert 4, Larry W. Oberley 4, and James M. Phang 1*

1 Metabolism and Cancer Susceptibility Section, Laboratory for Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702
2 Basic Research Program, SAIC-Frederick, Inc., Frederick, MD 21702
3 Department of Biochemistry and Molecular Biology, University of New Mexico Health Science Center, Albuquerque, New Mexico
4 Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242

* To whom correspondence should be addressed.
James M. Phang, E-mail: phang{at}ncifcrf.gov


  Abstract

Proline oxidase (POX), localized at inner mitochondrial membranes, is encoded by a p53-induced gene and metabolically participates in p53-induced apoptosis. Previously we showed that POX catalyzed the generation of reactive oxygen species (ROS). We and others have demonstrated that overexpression of POX, independent of p53, causes apoptotic cell death in a variety of cancer cells. But a necessary role for ROS remains uncertain. Therefore, we asked whether superoxide dismutases (SOD) and catalase, important antioxidant enzymes, might interfere with the POX-dependent induction of apoptosis. In this study, we used DLD-1 colorectal cancer cells stably transfected with the POX gene under the control of a tetracycline-inducible promoter. When doxycycline was removed from the culture medium and the expression of POX was induced, apoptotic cell death was initiated. To examine the importance of the ROS-dependent component of the pathway, we infected DLD-1 POX cells with recombinant adenoviruses containing MnSOD, CuZnSOD, catalase, or varying combinations of these adenoviruses followed by induced expression of POX. The expression of MnSOD inhibited POX-induced apoptosis, but others did not. Mechanistically mitochondria-localized MnSOD dramatically reduced the release of cytochrome c to cytosol by POX. Compared with control cells, MnSOD-expressing DLD-1 POX cells generated a higher concentration of H2O2 due to dismutation of superoxide radicals, which was elevated by POX. Thus, these data further suggest that the generation of superoxide radicals plays a crucial role in POX-induced apoptosis and the process is partially blocked by MnSOD.

Keywords: proline oxidase; MnSOD; superoxide radicals; apoptosis.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
Y. Liu, G. L. Borchert, S. P. Donald, B. A. Diwan, M. Anver, and J. M. Phang
Proline Oxidase Functions as a Mitochondrial Tumor Suppressor in Human Cancers
Cancer Res., August 15, 2009; 69(16): 6414 - 6422.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
J. M. Phang, J. Pandhare, and Y. Liu
The Metabolism of Proline as Microenvironmental Stress Substrate
J. Nutr., October 1, 2008; 138(10): 2008S - 2015S.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Qiu, K. J. Aiken, A. L. Chokas, D. E. Beachy, and H. S. Nick
Distinct Functions of CCAAT Enhancer-binding Protein Isoforms in the Regulation of Manganese Superoxide Dismutase during Interleukin-1{beta} Stimulation
J. Biol. Chem., September 19, 2008; 283(38): 25774 - 25785.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
N. Krishnan, A. R. Doster, G. E. Duhamel, and D. F. Becker
Characterization of a Helicobacter hepaticus putA Mutant Strain in Host Colonization and Oxidative Stress
Infect. Immun., July 1, 2008; 76(7): 3037 - 3044.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. Cooper, J. Pandhare, S. P. Donald, and J. M. Phang
A Novel Function for Hydroxyproline Oxidase in Apoptosis through Generation of Reactive Oxygen Species
J. Biol. Chem., April 18, 2008; 283(16): 10485 - 10492.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. A. White, N. Krishnan, D. F. Becker, and J. J. Tanner
Structure and Kinetics of Monofunctional Proline Dehydrogenase from Thermus thermophilus
J. Biol. Chem., May 11, 2007; 282(19): 14316 - 14327.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
D. K. Bideshi, M.-V. Demattei, F. Rouleux-Bonnin, K. Stasiak, Y. Tan, S. Bigot, Y. Bigot, and B. A. Federici
Genomic Sequence of Spodoptera frugiperda Ascovirus 1a, an Enveloped, Double-Stranded DNA Insect Virus That Manipulates Apoptosis for Viral Reproduction
J. Virol., December 1, 2006; 80(23): 11791 - 11805.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
C. Chen, S. Wanduragala, D. F. Becker, and M. B. Dickman
Tomato QM-Like Protein Protects Saccharomyces cerevisiae Cells against Oxidative Stress by Regulating Intracellular Proline Levels.
Appl. Envir. Microbiol., June 1, 2006; 72(6): 4001 - 4006.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Pandhare, S. K. Cooper, and J. M. Phang
Proline Oxidase, a Proapoptotic Gene, Is Induced by Troglitazone: EVIDENCE FOR BOTH PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {gamma}-DEPENDENT AND -INDEPENDENT MECHANISMS
J. Biol. Chem., January 27, 2006; 281(4): 2044 - 2052.
[Abstract] [Full Text] [PDF]


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.