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

• Published in: FEBS letters Vol. 365; no. 1; pp. 66 - 70
• Main Authors: Sandstrom, Paul A., Pardi, Diane, Tebbey, Paul W., Dudek, Ronald W., Terrian, David M., Folks, Thomas M., Buttke, Thomas M.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 22.05.1995
• Subjects: acid; Antioxidant; Apoptosis - drug effects; BAPTA-AM, 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester; Calcium - analysis; Cell death; Cell Nucleus - pathology; Cell Nucleus - ultrastructure; Cells, Cultured; Dose-Response Relationship, Drug; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; HPETE, hydroperoxyeicosatetraenoic; HPODE; Humans; hydroperoxydodecadienoic acid; Leukotrienes - pharmacology; Linoleic Acids - pharmacology; Lipid Peroxidation; Lipid Peroxides - pharmacology; Lymphocyte; Membrane lipid; MTS, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H -tetrazolium, inner salt); Oxygen radical; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; ROS, reactive oxygen species; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; T-Lymphocytes - ultrastructure; TNF-α, tumor necrosis factor-α; BAPTA-AM, 1,2-bis( O-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid acetoxymethyl ester; Oxygen radical; hydroperoxydodecadienoic acid; HPETE, hydroperoxyeicosatetraenoic; MTS, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium, inner salt); Antioxidant; Membrane lipid; acid; TNF-α, tumor necrosis factor-α; HPODE; Cell death; ROS, reactive oxygen species; Lymphocyte
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00443-D

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.