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

E. Pocsik, R. Mihalik, M. Penzes, H. Loetscher, H. Gallati, B. B. Aggarwal

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)303-316
Number of pages14
JournalJournal of Cellular Biochemistry
Volume59
Issue number3
DOIs
Publication statusPublished - 1995

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Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor Receptors
Cell Cycle
Cells
Cell Division
Thymidine
S Phase
Modulation
Demecolcine
Hydroxyurea
Level control
Etoposide
Lymphoma, Large B-Cell, Diffuse
G2 Phase
G1 Phase
Cell Surface Receptors
human TNFRSF1B protein
Cell Size
Proteins
Tumor Necrosis Factor-alpha

Keywords

  • human histiocytic lymphoma
  • p60
  • p80
  • protein synthesis
  • receptors
  • TNF

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

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. / Pocsik, E.; Mihalik, R.; Penzes, M.; Loetscher, H.; Gallati, H.; Aggarwal, B. B.

In: Journal of Cellular Biochemistry, Vol. 59, No. 3, 1995, p. 303-316.

Research output: Contribution to journalArticle

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abstract = "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.",
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