Document Detail


Carcinogenic heavy metals replace Ca2+ for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer.
MedLine Citation:
PMID:  20655937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mono-ubiquitinated annexin A1 was purified from rat liver nuclei. The homodimer form of mono-ubiquitinated annexin A1 was able to unwind dsDNA in a Mg(2+)- and ATP-dependent manner, and to anneal ssDNA in a Ca(2+)-dependent manner. Phospholipids decreased the concentration of Ca(2+) required for maximal annealing activity. Heavy metals such as As(3+), Cr(6+), Pb(2+) and Cd(2+) substituted for Ca(2+) in the ssDNA binding and annealing activities of annexin A1. While these metals inhibited the unwinding of dsDNA by nuclear annexin A1 in the presence of Mg(2+) and ATP, they enhanced dsDNA-dependent ATPase activity of annexin A1. Heavy metals may have produced dsDNA, a substrate for the DNA unwinding reaction, via the DNA annealing reaction. DNA synthesomes were isolated from L5178Y tk(+/-) mouse lymphoma cells in exponential growth, and were found to contain helicase activities. The As(3+)- or Cr(6+)-induced increases in ssDNA binding activity of DNA synthesomes were reduced by a mono-specific anti-annexin A1 antibody, but not by anti-Ig antibody. Anti-annexin A1 antibody also blocked the inhibitory and stimulatory effects of As(3+) or Cr(6+) towards DNA unwinding and annealing activities of DNA synthesomes. Based on these observations, it can be concluded that the effects of heavy metals on DNA annealing and unwinding activities are mediated, at least in substantial part, through actions of the mono-ubiquitinated annexin A1 homodimer.
Authors:
Aiko Hirata; George B Corcoran; Fusao Hirata
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-22
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  248     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-10     Completed Date:  2010-10-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  45-51     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / metabolism
Adenosine Triphosphate / metabolism
Animals
Annexin A1 / metabolism*
Calcium / metabolism*
Carcinogens / toxicity*
Cell Line, Tumor
Cell Nucleus / metabolism
DNA / metabolism
DNA Helicases / metabolism
Liver / metabolism
Lymphoma / metabolism
Magnesium / metabolism
Metals, Heavy / toxicity*
Mice
Phospholipids / pharmacology
Rats
Grant Support
ID/Acronym/Agency:
5R01 ES10814/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Annexin A1; 0/Carcinogens; 0/Metals, Heavy; 0/Phospholipids; 56-65-5/Adenosine Triphosphate; 7439-95-4/Magnesium; 7440-70-2/Calcium; 9007-49-2/DNA; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/DNA Helicases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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