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

Biochim Biophys Acta. 2014 Feb;1843(2):265-74. doi: 10.1016/j.bbamcr.2013.10.020. Epub 2013 Oct 31.

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.

Keywords: Human T lymphocyte; Intracellular localization; Microvesicle secretion; SOD-1; T cell activation; TCR triggering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Brefeldin A / pharmacology
  • CD3 Complex / metabolism
  • Cell Aggregation / drug effects
  • Cluster Analysis
  • Cytoplasmic Vesicles / drug effects
  • Cytoplasmic Vesicles / metabolism
  • Enzyme Induction / drug effects
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / enzymology*
  • Lymphocyte Activation* / drug effects
  • Protein Transport / drug effects
  • Reactive Oxygen Species / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Superoxide Dismutase / biosynthesis*
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*

Substances

  • CD3 Complex
  • Reactive Oxygen Species
  • Receptors, Antigen, T-Cell
  • SOD1 protein, human
  • Brefeldin A
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Acetylcysteine