Document Detail


Reaction of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) Cu(II) with Ehrlich cells. Binding of copper to metallothionein and its relationship to zinc metabolism and cell proliferation.
MedLine Citation:
PMID:  4055754     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The copper complex of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) or CuKTS is reduced and dissociated upon reaction with Ehrlich cells. Titration of the cells with the complex leads to the specific binding of copper to metallothionein with 1 to 1 displacement of its complement of zinc. Under conditions of complete titration of metallothionein, 1.25-2.5 nmol CuKTS/10(7) cells, cellular DNA synthesis is rapidly inhibited but no long term effects on cell proliferation are observed. The kinetics of redistribution of Cu and Zn in Ehrlich cells in culture and in animals were studied after pulse reaction of CuKTS with cells. After exposure of cells to the noncytotoxic concentration of 2.5 nmol of CuKTS/10(7) cells, nonmetallothionein bound copper is lost rapidly from the cells, after which copper in metallothionein decays. New zinc metallothionein is made as soon as exposed cells are placed in culture. New synthesis stops when the level of zinc in metallothionein reaches control levels. A second pulse treatment of cells with CuKTS to displace zinc from metallothionein again stimulates new synthesis of the protein to restore its normal concentration. The kinetics of metal metabolism in Ehrlich cells exposed to 5.5 nmol of CuKTS/10(7) cells, which inhibits cell proliferation, are qualitatively similar except there is a pronounced lag before new zinc metallothionein is synthesized. The Ehrlich ascites tumor in mice responds to CuKTS similarly to cells in culture. It is also shown that cultured Ehrlich cells do not make extra zinc metallothionein in the presence of high levels of ZnCl2, and fail to accumulate copper in the presence of large concentrations of CuCl2.
Authors:
A Kraker; S Krezoski; J Schneider; D Minkel; D H Petering
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  260     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1985 Nov 
Date Detail:
Created Date:  1985-12-05     Completed Date:  1985-12-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  13710-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / metabolism*,  pharmacology
Carcinoma, Ehrlich Tumor / metabolism*,  pathology
Cell Division
Cells, Cultured
Chlorides*
Copper / metabolism*,  pharmacology
Female
Kinetics
Metallothionein / metabolism*
Mice
Mice, Inbred ICR
Organometallic Compounds*
Thiosemicarbazones / metabolism*,  pharmacology
Time Factors
Zinc / metabolism*,  pharmacology
Zinc Compounds*
Grant Support
ID/Acronym/Agency:
GM-29583/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Chlorides; 0/Organometallic Compounds; 0/Thiosemicarbazones; 0/Zinc Compounds; 14186-84-6/3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato)copper(II); 7440-50-8/Copper; 7440-66-6/Zinc; 7447-39-4/cupric chloride; 7646-85-7/zinc chloride; 9038-94-2/Metallothionein

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


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