Manganese superoxide dismutase: a regulator of T cell activation-induced oxidative signaling and cell death
Mitochondrial reactive oxygen species (ROS) are indispensible for T cell activation-induced expression of interleukin 2 (IL-2) and CD95 ligand (CD95L, FasL/Apo-1L) genes, and in turn, for CD95L-mediated activation-induced cell death (AICD). Here, we show that manganese superoxide dismutase (MnSOD/SO...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
9 March 2012
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| In: |
Biochimica et biophysica acta
Year: 2012, Jahrgang: 1823, Heft: 5, Pages: 1041-1052 |
| ISSN: | 1878-2434 |
| DOI: | 10.1016/j.bbamcr.2012.03.003 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1016/j.bbamcr.2012.03.003 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0167488912000638 
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| Verfasserangaben: | Marcin Mikołaj Kamiński, Daniel Röth, Sabine Sass, Sven Wolfgang Sauer, Peter Heinrich Krammer, Karsten Gülow |
| Zusammenfassung: | Mitochondrial reactive oxygen species (ROS) are indispensible for T cell activation-induced expression of interleukin 2 (IL-2) and CD95 ligand (CD95L, FasL/Apo-1L) genes, and in turn, for CD95L-mediated activation-induced cell death (AICD). Here, we show that manganese superoxide dismutase (MnSOD/SOD2), a major mitochondrial antioxidative enzyme, constitutes an important control switch in the process of activation-induced oxidative signal generation in T cells. Analysis of the kinetics of T cell receptor (TCR)-triggered ROS production revealed a temporal association between higher MnSOD abundance/activity and a shut-down phase of oxidative signal generation. Transient or inducible MnSOD overexpression abrogated T cell activation-triggered mitochondrial ROS production as well as NF-κB- and AP-1-mediated transcription. Consequently, lowered expression of IL-2 and CD95L genes resulted in decreased IL-2 secretion and CD95L-dependent AICD. Moreover, upregulation of the mitochondrial MnSOD level is dependent on oxidation-sensitive transcription and not on the increase of mitochondrial mass. Thus, MnSOD-mediated negative feedback regulation of activation-induced mitochondrial ROS generation exemplifies a process of retrograde mitochondria-to-nucleus communication. Our finding underlines the critical role for MnSOD and mitochondria in the regulation of human T cell activation. |
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| Beschreibung: | Gesehen am 12.04.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 1878-2434 |
| DOI: | 10.1016/j.bbamcr.2012.03.003 |