Lipid hydroperoxides induce apoptosis in T cells displaying a HIV-associated glutathione peroxidase deficiency.
8E5 is a chronically human immunodeficiency virus (HIV)-infected human T cell line, which we have previously shown to be extremely susceptible to hydrogen peroxide (H2O2)-induced apoptosis due to a HIV-associated catalase deficiency. Here we report that HIV gene expression additionally renders 8E5 cells 10-fold more sensitive than either uninfected A3.01 cells or HIV-infected but nonexpressing 8E5L cells to killing by 15-hydroperoxyeicosatetraenoic acid (15-HPETE), as well as several other hydroperoxy fatty acids. Whereas the viability of A3.01 and 8E5L cells was relatively unaffected by exposure to 10 microM 15-HPETE, similarly treated 8E5 cells underwent apoptosis, as demonstrated by morphological changes and the presence of fragmented DNA. The unique susceptibility of 8E5 cells was attributable to their inability to convert 15-HPETE to 15-hydroxy-eicosatetraenoic acid (15-HETE) owing to a marked reduction in glutathione peroxidase activity. Since oxidized lipids have been reported to accumulate in oxidatively stressed, HIV-infected individuals, a HIV-associated glutathione peroxidase deficiency may contribute to the depletion of CD4 T cells that occurs in the acquired immune deficiency syndrome (AIDS).
Sandstrom
P A
PA
Department of Microbiology and Immunology, East Carolina University, School of Medicine, Greenville, North Carolina 27858-4354.
Tebbey
P W
PW
Van Cleave
S
S
Buttke
T M
TM
D017209:Apoptosis; D002460:Cell Line; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000172:deficiency*; D005980:Glutathione Reductase / Q000378:metabolism; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000201:enzymology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism* / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000201:enzymology*
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione