Document Detail


Effect of cell cycle on the regulation of the cell surface and secreted forms of type I and type II human tumor necrosis factor receptors.
MedLine Citation:
PMID:  8567749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cell cycle has been shown to regulate the biological effects of human tumor necrosis factor (TNF), but to what extent that regulation is due to the modulation of TNF receptors is not clear. In the present report we investigated the effect of the cell cycle on the expression of surface and soluble TNF receptors in human histiocytic lymphoma U-937. Exposure to hydroxyurea, thymidine, etoposide, bisbensimide, and demecolcine lead to accumulation of cells primarily in G1/S, S, S/G2/M, G2/M, and M stages of the cell cycle, respectively. While no significant change in TNF receptors occurred in cells arrested in G1/S or S/G2 stages, about a 50% decrease was observed in cells at M phase of the cycle. Scatchard analysis showed a reduction in receptor number rather than affinity. In contrast, cells arrested at S phase (thymidine) showed an 80% increase in receptor number. The decrease in the TNF receptors was not due to changes in cell size or protein synthesis. The increase in receptors, however, correlated with an increase in total protein synthesis (to 3.8-fold of the control levels). A proportional change was observed in the p60 and p80 forms of the TNF receptors. A decrease in the surface receptors in cells arrested in M phase correlated with an increase in the amount of soluble receptors. The cellular response to TNF increased to 8- and 2-fold in cells arrested in G1 and S phase, respectively; but cells at G2/M phase showed about 6-fold decrease in response. In conclusion, our results demonstrate that the cell cycle plays an important role in regulation of cell-surface and soluble TNF receptors and also in the modulation of cellular response.
Authors:
E Pocsik; R Mihalik; M Penzes; H Loetscher; H Gallati; B B Aggarwal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  59     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1996-03-07     Completed Date:  1996-03-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  303-16     Citation Subset:  IM    
Affiliation:
Department of Immunology, National Institute of Haematology, Blood Transfusion, and Immunology, Budapest, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle* / drug effects
DNA / metabolism
DNA Topoisomerases, Type II / antagonists & inhibitors
Demecolcine / pharmacology
Enzyme Inhibitors / pharmacology
Etoposide / pharmacology
G1 Phase / drug effects
G2 Phase / drug effects
Hela Cells
Humans
Hydroxyurea / pharmacology
Leukemia, Erythroblastic, Acute
Lymphoma, Large B-Cell, Diffuse
Mitosis / drug effects
Nocodazole / pharmacology
Receptors, Tumor Necrosis Factor / metabolism*
S Phase / drug effects
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / metabolism
Vinblastine / pharmacology
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Receptors, Tumor Necrosis Factor; 0/Tumor Necrosis Factor-alpha; 127-07-1/Hydroxyurea; 31430-18-9/Nocodazole; 33419-42-0/Etoposide; 477-30-5/Demecolcine; 865-21-4/Vinblastine; 9007-49-2/DNA; EC 5.99.1.3/DNA Topoisomerases, Type II

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