BCL-2 PROTECTS FROM OXIDATIVE DAMAGE AND APOPTOTIC CELL-DEATH WITHOUTINTERFERING WITH ACTIVATION OF NF-KAPPA-B BY TNF

The recent demonstration of the anti-oxidant properties of the Bcl-2 g ene product suggested that expression of Bcl-2 may interfere with the nuclear migration of the NF-kappa B transcription factor, which is tho ught to depend on the presence of reactive oxygen intermediates. In mo use L cells, overexpression of Bcl-2 interfered with the activation of NF-kappa B by H2O2. However, Bcl-2 had no effect on the activation of NF-kappa B by TNF, even though it protected cells from TNF-induced ap optosis. The effects of exogenous pyrrolidine dithiocarbamate were ver y similar to those of Bcl-2 overexpression. We conclude that the prote ctive effects of anti-oxidants against induced apoptotic cell death ar e unrelated to their ability to interfere with NF-kappa B activation.