Manganese superoxide dismutase

• Verfasst von: Kamiński, Marcin [VerfasserIn]
• Verfasst von: Röth, Daniel [VerfasserIn]
• Verfasst von: Sass, Sabine [VerfasserIn]
• Verfasst von: Sauer, Sven [VerfasserIn]
• Titel: Manganese superoxide dismutase
• Titelzusatz: a regulator of T cell activation-induced oxidative signaling and cell death
• Verf.angabe: Marcin Mikołaj Kamiński, Daniel Röth, Sabine Sass, Sven Wolfgang Sauer, Peter Heinrich Krammer, Karsten Gülow
• E-Jahr: 2012
• Jahr: 9 March 2012
• Umfang: 12 S.
• Teil: volume:1823
• Teil: year:2012
• Teil: number:5
• Teil: pages:1041-1052
• Teil: extent:12
• Fussnoten: Gesehen am 12.04.2018
• Titel Quelle: Enthalten in: Biochimica et biophysica acta
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1947
• Jahr Quelle: 2012
• Band/Heft Quelle: 1823(2012), 5, Seite 1041-1052
• ISSN Quelle: 1878-2434
• DOI: doi:10.1016/j.bbamcr.2012.03.003
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Activation-induced cell death (AICD)
• Sach-SW: IL-2 and CD95L/FasL
• Sach-SW: Manganese superoxide dismutase (MnSOD/SOD2)
• Sach-SW: Mitochondria
• Sach-SW: Reactive oxygen species (ROS)
• Sach-SW: T cell activation
• K10plus-PPN: 1571937919

Abstract

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.