| Carcinogenic heavy metals replace Ca2+ for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer. | |
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MedLine Citation:
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PMID: 20655937 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Aiko Hirata; George B Corcoran; Fusao Hirata |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-22 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 248 ISSN: 1096-0333 ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-10 Completed Date: 2010-10-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 45-51 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphatases
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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:
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5R01 ES10814/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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