T cell activation induces CuZn superoxide dismutase (SOD)-1 intracellular re-localization, production and secretion

Abstract

Reactive oxygen species (ROS) behave as second messengers in signal transduction for a series of receptor/ligand interactions. A major regulatory role is played by hydrogen peroxide (H2O2), more stable and able to freely diffuse through cell membranes. Copper-zinc superoxide dismutase (CuZn-SOD)-1 is a cytosolic enzyme involved in scavenging oxygen radicals to H2O2 and molecular oxygen, thus representing a major cytosolic source of peroxides. Previous studies suggested that superoxide anion and H2O2 generation are involved in T cell receptor (TCR)-dependent signaling. Here, we describe that antigen-dependent activation of human T lymphocytes significantly increased extracellular SOD-1 levels in lymphocyte cultures. This effect was accompanied by the synthesis of SOD-1-specific mRNA and by the induction of microvesicle SOD-1 secretion. It is of note that SOD-1 increased its concentration specifically in T cell population, while no significant changes were observed in the "non-T" cell counterpart. Moreover, confocal microscopy showed that antigen-dependent activation was able to modify SOD-1 intracellular localization in T cells. Indeed, was observed a clear SOD-1 recruitment by TCR clusters. The ROS scavenger N-acetylcysteine (NAC) inhibited this phenomenon. Further studies are needed to define whether SOD-1-dependent superoxide/peroxide balance is relevant for regulation of T cell activation, as well as in the functional cross talk between immune effectors.

The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme

“…These and previous data pointed out that SOD1, through an increase of calcium-dependent signaling, could affect different biological functions besides acting as scavenger of superoxide radical. The paracrine role carried out by SOD1 could also explain the other function ascribed to this protein (Mondola et al, 2002; De Felice et al, 2004; Viggiano et al, 2012; Terrazzano et al, 2014). …”

Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding

“…The activation of T-cells has been shown to induce the rapid production of reactive oxygen species [25] through superoxide dismutases [26, 27] as well as NADPH oxidase [28]. The role of redox signaling as a modulator of T-cell activity is just beginning to be elucidated [29].…”

Avaliação sistemática do uso do Dried Blood Spot para determinação de elementos químicos em sangue capilar visando estudos de biomonitoramento no Brasil

“…Sua essencialidade se deve ao fato de ser cofator indispensável de várias enzimas presentes nos mamíferos. Ele está envolvido nos processos de divisão celular, crescimento, cicatrização, regulação do metabolismo e do sistema imunológico (KNOELL; LIU, 2010;MAGGINI, 2010;MOCCHEGIANI et al, 2010;TERRAZZANO et al, 2014).…”

“…Já seus compostos são amplamente utilizados tanto na produção de tintas brancas e cerâmicas, , 2010;MAGGINI, 2010;MOCCHEGIANI et al, 2010;TERRAZZANO et al, 2014).…”

“…Sua essencialidade se deve ao fato de ser cofator indispensável de várias enzimas presentes nos mamíferos. Ele está envolvido nos processos de divisão celular, crescimento, cicatrização, regulação do metabolismo e do sistema imunológico (KNOELL; LIU, 2010;MAGGINI, 2010;MOCCHEGIANI et al, 2010;TERRAZZANO et al, 2014).Os sintomas da deficiência de Zn estão relacionados principalmente ao aumento da susceptibilidade a infecções, devido à menor ação das células T do sistema imunológico, que são responsáveis pela resposta biológica do organismo contra células infectadas, fungos, parasitas e tecidos estranhos (KLOUBERT; RINK, 2015;PRASAD, 2009;SANDSTEAD, 1995;WALRAVENS, 1980). O Zn atua também no metabolismo de glicose.…”