Document Detail


Quantitative correlation between cellular proliferation and nuclear poly (ADP-ribose) polymerase (PARP-1).
MedLine Citation:
PMID:  16391829     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment of cells with lysophosphatidyl choline and centrifugal extraction can separate poly (ADP-ribose) synthetase (PARP-1) and DNA synthetase activities, permitting the experimental analysis and comparison of both multienzyme systems. Only PARP-1 is being assayed by our system. Ca(2+) and Mg(2+) have minor activating effects, and added histones are without activating action. Short end-blocked dsDNAs at nM concentrations and spermine at mM concentrations are maximally activating coenzymes of poly (ADP-ribose) synthesis. Comparison of non-proliferating non-malignant cells with rapidly growing cancer cells demonstrates that rates of poly (ADP-ribose) synthesis and DNA synthesis are highest in pre-confluent non-malignant cells and in proliferating cancer cells, and lowest in contact-inhibited non-malignant cells. Rates of poly (ADP-ribose) synthesis correlate with the number of enzymatically activable PARP-1 molecules per cell, determined under Vmax conditions where activity is linearly proportional to enzyme protein. Contact-inhibited non-malignant cells exhibit only trans-ADP-ribosylation that is not affected by ATP, while rapid growth, especially in cancer cells, demonstrates extensive auto-poly (ADP)-ribosylation that is strongly inhibited by ATP at concentrations present in cells exhibiting normal bioenergetics. Rates of mRNA synthesis in non-proliferating non-malignant cells and in cancer cells were indistinguishable, indicating that the differences observed between cellular phenotypes are most likely due to reassembly of PARP-1 molecules in nuclei to homo-dimers (in cancer cells) and hetero-dimers (in non-cancer cells). A specific inhibitor and an inactivator of PARP-1 each inhibit DNA synthesis when intact cancer cells are pretreated with these drugs. Direct addition of these drugs to permeabilized cells performing DNA synthesis has no effect on DNA synthesis. The most striking diagnostic signal for cancer cells is activation of PARP-1 and of DNA synthesis.
Authors:
Ernest Kun; Eva Kirsten; Pal I Bauer; Charles P Ordahl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  17     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-04     Completed Date:  2006-03-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  293-300     Citation Subset:  IM    
Affiliation:
Department of Anatomy, School of Medicine, University of California San Francisco Medical Center, San Francisco, CA 94143, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Proliferation
Cercopithecus aethiops
DNA / biosynthesis
Electrophoresis, Gel, Two-Dimensional
Kinetics
Neoplasms / metabolism,  pathology
Poly(ADP-ribose) Polymerases / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
HL 35561/HL/NHLBI NIH HHS; HL 59693/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 9007-49-2/DNA; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

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


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