LIPID HYDROPEROXIDE-INDUCED APOPTOSIS - LACK OF INHIBITION BY BCL-2 OVER-EXPRESSION

Increased membrane lipid peroxidation has recently been implicated as being associated with apoptosis, In the present study the addition of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) or 13-hydroperoxydodeca dienoic acid (13-HPODE) to A3.01 T cells is shown to induce marked chr omatin condensation coincident with DNA fragmentation, indicative of a poptosis, 15-HPETE also evoked an immediate and sustained rise in cyto plasmic calcium which was required for the induction of apoptosis, A3. 01 cells transfected with the bcl-2 proto-oncogene were 6- to 8-fold m ore resistant to apoptotic killing by tumor necrosis factor-alpha, but only 0.4-fold more resistant to 15-HPETE. Thus, Bcl-2 is not capable of protecting cells from undergoing apoptosis following the direct add ition of lipid hydroperoxides.