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-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-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 addition of lipid hydroperoxides.
Sandstrom
P A
PA
Retrovirus Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Pardi
D
D
Tebbey
P W
PW
Dudek
R W
RW
Terrian
D M
DM
Folks
T M
TM
Buttke
T M
TM
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D002467:Cell Nucleus / Q000473:pathology / Q000648:ultrastructure; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015289:Leukotrienes / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
D015289:Leukotrienes; D008041:Linoleic Acids; D008054:Lipid Peroxides; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D004533:Egtazic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D002118:Calcium