Document Detail


Deregulation of catalase, not MnSOD, is associated with necrotic death of p53-defective DF-1 cells under antimycin A-induced oxidative stress.
MedLine Citation:
PMID:  15528999     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of distinct genetic alterations in spontaneously immortalized DF-1 cells was found to be dysfunction of p53 and E2F-1 as well as altered antioxidant gene expression (upregulation of MnSOD and downregulation of catalase). We have characterized the cellular responses of primary and immortal DF-1 cells to oxidative stress and found that DF-1 cells were more sensitive to oxidative stress than their primary counterparts when treated with antimycin A. The increased DF-1 cell death by oxidative stress was accompanied by an increase in the levels of intracellular superoxide anions and hydrogen peroxide. The cell death in DF-1 cells by antimycin A showed none of the hallmarks of apoptosis, but displayed a significantly increased necrotic cell population. Anti-apoptotic Bcl-2 failed to inhibit oxidative-induced necrotic cell death in the DF-1 cells. However, this necrotic cell death was significantly decreased by treatment with hydrogen peroxide scavengers such as sodium pyruvate and N-acetyl-cysteine. Interestingly, overexpression of human catalase in DF-1 cells endowed cells resistant to the oxidative stress by antimycin A treatment, although the downregulation of MnSOD by an antisense strategy showed no evident change in the cytotoxic effect caused by antimycin A. Taken together, the present study might provide new therapeutic approach for tumor cells having the loss of p53 function and the altered antioxidant functions.
Authors:
Seungkwon You; Byung-Whi Kong; Sun-Young Jeon; Douglas N Foster; Hyunggee Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecules and cells     Volume:  18     ISSN:  1016-8478     ISO Abbreviation:  Mol. Cells     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-11-05     Completed Date:  2005-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9610936     Medline TA:  Mol Cells     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  220-9     Citation Subset:  IM    
Affiliation:
Laboratory of Cell Growth and Function Regulation, College of Life and Environmental Sciences, Korea University, Seoul 136-701, Korea. bioseung@korea.ac.kr
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimycin A / pharmacology
Catalase / genetics,  physiology*
Cell Line
Chick Embryo
Fibroblasts / metabolism,  pathology*
Free Radical Scavengers / pharmacology
Gene Expression Regulation, Enzymologic / drug effects,  physiology*
Humans
Necrosis
Oxidative Stress*
Superoxide Dismutase / genetics,  physiology*
Transfection
Tumor Suppressor Protein p53 / deficiency*
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Tumor Suppressor Protein p53; 642-15-9/Antimycin A; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase

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