Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-kappa B

Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. This study shows that hydrogen peroxide-induced apoptosis in T-cells did not require tyrosine kinase p56(lck), phosphatase CD45, the CD95 receptor and its associated Caspase-8, H2O2-triggered cell d eath led to the induced cleavage and activation of Caspase-3, Hydrogen pero xide-treatment of T-cells resulted in the formation of mitochondrial permea bility transition pores, a rapid decrease of the mitochondrial transmembran e potential Delta Psi(m) and the release of Cytochrome C, Inhibition of the mitochondrial permeability transition by bongkrekic acid (BA), or interfer ence with the mitochondrial electron transport system by rotenone or menadi one prevented the cytotoxic effect of H2O2, Antimycin A, a mitochondrial in hibitor that increases the release of mitochondrial ROS (MiROS), enhanced a poptosis. Overexpression of Bcl-2 and the viral anti-apoptotic proteins BHR F-1 and E1B 19K counteracted H2O2-induced apoptosis, Pharmacological and ge netic inhibition of transcription factor NF-kappa B protected cells from hy drogen peroxide-elicited cell death. This detrimental effect of NF-kappa B mediating hydrogen peroxide-induced cell death presumably relies on the ind uced expression of death effector genes such as p53, which was NF-kappa B-d ependently upregulated in the presence of H2O2.