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Inhibition of Fas-induced apoptotic cell death by osmotic cell shrinkage
E Gulbins1, J Welsch, A Lepple-Wienhuis
1Department of Physiology, University of Tuebingen, Germany.
Abstract:
Apoptosis is an active physiological mechanism permitting the elimination of cells by triggering an intracellular signalling cascade. Here, we tested whether osmotic alterations of cell volume interfere with apoptotic cell death in Jurkat T-lymphocytes. Apoptotic cell death of Jurkat cells was elicited by activation of the Fas receptor which results in sphingomyelinase stimulation, release of ceramide, activation of Ras, Rac-proteins and formation of O2. Osmotic cell shrinkage inhibited apoptotic cell death induced by the Fas receptor in Jurkat T-lymphocytes. Osmotic cell shrinkage did not interfere with Fas induced activation of the acidic sphingomyelinase or activation of Ras but impaired the formation of O2 suggesting an important function of cell volume in the synthesis of reactive oxygen intermediates upon Fas receptor ligation.
Insights
Osmotic cell shrinkage inhibits apoptosis in Jurkat T-lymphocytes by interfering with Fas receptor-induced reactive oxygen intermediate formation. Cell volume plays a crucial role in this signaling pathway.
Area of Science:
- Cell biology
- Immunology
- Physiology
Background:
- Apoptosis is a regulated cell death process essential for tissue homeostasis.
- The Fas receptor pathway initiates apoptosis through intracellular signaling cascades.
- Cell volume regulation is critical for cellular functions.
Purpose of the Study:
- To investigate the impact of osmotic cell volume alterations on Fas receptor-mediated apoptosis.
- To determine how cell shrinkage affects the signaling pathway components involved in apoptosis.
Main Methods:
- Jurkat T-lymphocytes were subjected to osmotic cell shrinkage.
- Apoptosis was induced via Fas receptor activation.
- Sphingomyelinase activity, Ras activation, and reactive oxygen species (ROS) formation were measured.
Main Results:
- Osmotic cell shrinkage significantly inhibited Fas receptor-induced apoptosis in Jurkat T-lymphocytes.
- Cell shrinkage did not affect Fas-induced sphingomyelinase or Ras activation.
- However, cell shrinkage impaired the formation of reactive oxygen species (ROS) downstream of Fas receptor activation.
Conclusions:
- Cell volume is a critical regulator of Fas receptor-mediated apoptosis.
- Impaired ROS synthesis due to cell shrinkage is a key mechanism by which apoptosis is inhibited.
- These findings highlight the interplay between cell volume and apoptotic signaling pathways.