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[Cell sensitivity to Fas-mediated apoptosis depends on three forms of Fas-antigen]
I V Beletskaia1, L F Nazarova, L V Nikonova
1Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Russia.
Abstract:
It is known that binding of specific anti-Fas antibodies to Fas-receptor induces apoptosis in various cell lines. But the mechanisms of functional regulation and realization of apoptosis remain so far unknown. We obtained HeLa cells transfected with cDNA of Fas-antigen, whose expression was located under the promoter controlled by isopropoyl beta-D-thiogalactopiranoside. Analysis of transfectants has shown that expression of Fas above a certain critical level leads to redistribution of Fas in the cells and is accompanied by changes in the cell cycles and cell sensitivity to the cytotoxic effects of anti-Fas and tumor necrosis factor (TNF). We propose that the sensitivity of cells to Fas-mediated apoptosis depends on the ratio of transmembrane, intracellular and soluble Fas-antigen in the cells.
Insights
This study reveals that high levels of Fas-antigen expression trigger cell cycle changes and alter sensitivity to apoptosis. The balance of Fas-antigen forms (transmembrane, intracellular, soluble) likely dictates cell death responses.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Fas receptor activation by anti-Fas antibodies induces apoptosis in various cell lines.
- The precise mechanisms regulating Fas-mediated apoptosis remain incompletely understood.
Purpose of the Study:
- To investigate the functional regulation and realization of Fas-mediated apoptosis.
- To analyze the impact of Fas-antigen expression levels on cell cycle and apoptosis sensitivity.
Main Methods:
- HeLa cells were transfected with Fas-antigen cDNA under an inducible promoter (isopropoyl beta-D-thiogalactopiranoside).
- Analysis of transfectants to assess Fas redistribution, cell cycle changes, and sensitivity to cytotoxic agents (anti-Fas, TNF).
Main Results:
- Elevated Fas-antigen expression above a critical threshold caused Fas redistribution within cells.
- Increased Fas expression correlated with alterations in cell cycle progression.
- Cells with higher Fas expression exhibited modified sensitivity to anti-Fas antibodies and tumor necrosis factor (TNF).
Conclusions:
- Fas-mediated apoptosis sensitivity is influenced by the expression level of Fas-antigen.
- The ratio of transmembrane, intracellular, and soluble Fas-antigen forms may be a key regulatory factor in apoptosis induction.