Publikation: Modification of apoptosis-related genes and CD95 signaling in cytokine-treated astrocytes
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Inflammatory activation of astrocytes with a complete cytokine mix consisting of tumor necrosis factor, interleukin-1 and interferon-gamma renders these otherwise resistant cells highly susceptible to cell death induction via the CD95 pathway. In dying cells, we observed several classical apoptotic features such as chromatin condensation and cytoplasmic blebbing. These events were however quickly followed by a rupture of the cell membrane. For a screen of the transcriptional changes taking place during the transformation from a CD95L-resistant to a CD95L-sensitive cell, we employed a small custom-spotted oligonucleotide microarray. The significantly regulated mRNA species were then further analyzed over a 24 h period by quantitative PCR. We observed a complex pattern of transcriptional regulations showing changes of pro-apoptotic genes (cd95, caspase-8, bid, bak, caspase-11), as well as anti-apoptotic genes (c-flip, iap-1, iap-2/3, bcl-2). Since inflammatory astrocyte sensitization increased linearly with the time of cytokine-treatment the anti-apoptotic genes never seemed to be able to take over a dominating role in this model. Finally, the response of activated astrocytes to CD95 stimulation was compared with several other death-inducing stimuli. Cells became also more sensitive towards the classical apoptosis inducer staurosporine, but not towards necrotic stimuli such as H2O2 and N-Methyl-N-nitro-N-nitrosoguanidine.
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FALSIG, Jeppe, Peter PÖRZGEN, Marcel LEIST, 2004. Modification of apoptosis-related genes and CD95 signaling in cytokine-treated astrocytes. In: Signal Transduction. 2004, 1/2(1-2), pp. 17-28. ISSN 1615-4053. eISSN 1615-4061. Available under: doi: 10.1002/sita.200400031BibTex
@article{Falsig2004Modif-6547, year={2004}, doi={10.1002/sita.200400031}, title={Modification of apoptosis-related genes and CD95 signaling in cytokine-treated astrocytes}, number={1-2}, volume={1/2}, issn={1615-4053}, journal={Signal Transduction}, pages={17--28}, author={Falsig, Jeppe and Pörzgen, Peter and Leist, Marcel} }
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