Lipid hydroperoxide‐induced apoptosis: lack of inhibition by Bcl‐2 over‐expression

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Abstract
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‐hydroperoxydodecadienoic acid (13‐HPODE) to A3.01 T cells is shown to induce marked chromatin condensation coincident with DNA fragmentation, indicative of apoptosis. 15‐HPETE also evoked an immediate and sustained rise in cytoplasmic calcium which was required for the induction of apoptosis. A3.01 cells transfected with the bcl‐2 proto‐oncogene were 6‐ to 8‐fold more resistant to apoptotic killing by tumor necrosis factor‐α, 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 addition of lipid hydroperoxides.