Document Detail

Amplification and hyperexpression of the catalase gene in selenoperoxidase-deficient leukemia cells.
MedLine Citation:
PMID:  7872806     Owner:  NLM     Status:  MEDLINE    
Murine L1210 and human HL-60 leukemia cells grown for 5-7 days in medium containing 1% serum without selenium supplementation [Se(-) cells] were severely depressed in selenoperoxidase (SePX) activity relative to selenium-supplemented controls [Se(+) cells]. Catalase (CAT) activity in Se(-) cells was unaffected up to this point, but thereafter began to increase. Two manifestations of this increase have been differentiated for both cell lines: (a) short-term induction of CAT (up to approx. twofold) after 2-3 weeks, followed by (b) long-term selection for cells that irreversibly express much higher levels of CAT, e.g., > 100 times (L1210) and > 10 times (HL-60) the levels observed in Se(+) controls after approximately 20 weeks. Although superoxide dismutase, glutathione S-transferase, and glucose-6-P dehydrogenase activities were unchanged in Se(-) cells, GSH levels were elevated by 50-100%; like short-term CAT elevation, this could be reversed by supplying Se. Short-term Se(-) cells were more sensitive to H2O2-induced killing than Se(+) cells, evidently because SePX activity was important for peroxide detoxification. However, long-term Se(-) cells were markedly more resistant to H2O2 than Se(+) counterparts, consistent with the much higher levels of CAT in the former. Southern blot analysis revealed that the copy number of CAT DNA in a clone of long-term Se(-) L1210 cells was four- to fivefold greater than that in an Se(+) clone. Northern blot analysis of RNA from the same Se(-) clone showed a CAT mRNA level that was at least 40 times higher than that of the Se(+) control. Similar trends were observed for HL-60 cells. These results suggest that elevated CAT during long-term Se deprivation is a reflection of amplification and greater transcription of the CAT gene.
F Lin; V E Jackson; A W Girotti
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  317     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-29     Completed Date:  1995-03-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7-18     Citation Subset:  IM    
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 56226.
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MeSH Terms
Catalase / biosynthesis*,  genetics
DNA, Neoplasm / analysis
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Hydrogen Peroxide / pharmacology
Leukemia / enzymology*,  genetics
Peroxidases / genetics,  metabolism*
Proteins / genetics,  metabolism
RNA, Messenger / analysis
Restriction Mapping
Selenium / deficiency
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/DNA, Neoplasm; 0/Proteins; 0/RNA, Messenger; 0/Selenoproteins; 7722-84-1/Hydrogen Peroxide; 7782-49-2/Selenium; EC 1.11.1.-/Peroxidases; EC

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