alpha-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and
J Neuzil1, I Svensson, T Weber
1Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany. jneuzil@klp.med.uni-muenchen.de
Abstract:
Alpha-Tocopheryl succinate (alpha-TOS), but not a-tocopherol, triggered apoptosis in Jurkat T cells. Apoptosis was induced by alpha-TOS in a time- and concentration-dependent mode, and signs of apoptosis were visible at concentrations of alpha-TOS as low as 30 microM, and within 3-5 h after addition of the ester. Employing a specific fluorogenic substrate, caspase-3 was found to be activated rapidly in response to alpha-TOS at 50 microM. We also found that Jurkat T cells challenged with alpha-TOS, when exposed to the lysosomotropic weak base acridine orange, showed decreased lysosomal uptake of the dye. This is suggestive of the involvement of lysosomal destabilisation in apoptosis of the cells. Apoptosis of Jurkat T cells induced with alpha-TOS also involved a drop in the mitochondrial membrane potential, although this phenomenon occurred after the initiation of lysosomal rupture. All apoptotic features observed with alpha-TOS were very similar to those found when cross-linking of the Fas receptor triggered apoptosis. These findings are consistent with the recent idea that vitamin E can contribute to elimination of malignant cells by the induction of apoptosis, and can be of (patho)physiological significance.
Insights
Alpha-Tocopheryl succinate (alpha-TOS) induces apoptosis in Jurkat T cells by activating caspase-3 and destabilizing lysosomes. This vitamin E derivative shows promise in eliminating malignant cells.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Vitamin E derivatives are investigated for therapeutic potential.
- Apoptosis plays a crucial role in cellular homeostasis and disease.
- Jurkat T cells are a relevant model for studying T cell apoptosis.
Purpose of the Study:
- To investigate the apoptotic effects of alpha-Tocopheryl succinate (alpha-TOS) on Jurkat T cells.
- To elucidate the mechanisms underlying alpha-TOS-induced apoptosis.
Main Methods:
- Treatment of Jurkat T cells with varying concentrations of alpha-TOS.
- Assessment of apoptosis using caspase-3 activation assays.
- Evaluation of lysosomal membrane integrity via acridine orange uptake.
- Measurement of mitochondrial membrane potential.
Main Results:
- Alpha-TOS, but not alpha-tocopherol, induced apoptosis in a time- and concentration-dependent manner.
- Caspase-3 activation was observed at 50 microM alpha-TOS.
- Alpha-TOS treatment led to lysosomal destabilization and decreased mitochondrial membrane potential.
- Apoptotic features mimicked those induced by Fas receptor cross-linking.
Conclusions:
- Alpha-TOS effectively induces apoptosis in Jurkat T cells through lysosomal and mitochondrial pathways.
- The findings support the role of vitamin E in cancer therapy via apoptosis induction.
- Alpha-TOS-induced apoptosis may have significant (patho)physiological implications.
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