Impairment of the Mitochondrial Electron Chain Transport Prevents NF-κB Activation by Hydrogen Peroxide

A large body of work has been devoted to mechanisms leading to the activation of the transcription factor NF-κB in various cell types. Several studies have indicated that NF-κB activation by numerous stimuli depends on the intracellular generation of reactive oxygen species (ROS). In this report, we first demonstrated that inhibition of the electron transport chain by either rotenone or antimycine A gave rise to dose-dependent inhibition of NF-κB translocation induced by 150 μM of hydrogen peroxide (H2O2). Conversely, the impairment of the mitochondrial respiratory chain did not affect T lymphocyte treatment by TNF-α (tumor necrosis factor α) or pre-B lymphocyte treatment with LPS (lipopolysaccharide). We also showed that oligomycine which inhibits ATP synthase and FCCP, which uncouples respiration also led to dose-dependent inhibition of NF-κB activation by H2O2. All these inhibitors were also shown to inhibit mitochondrial respiration in lymphocytes assessed by oxygen comsuption. Although only a transient drop in ATP concentration was observed when lymphocytes were treated by H2O2, this effect was remarkably reinforced in the presence of oligomycine demonstrating the crucial role of ATP in the signal transduction pathway induced by H2O2.