Prevention of geranylgeranoic acid-induced apoptosis by phospholipid hydroperoxide glutathione peroxidase gene

✍ Scribed by Yoshihiro Shidoji; Kyoko Okamoto; Yasutoshi Muto; Sadaaki Komura; Nobuko Ohishi; Kunio Yagi

• Book ID: 102302008
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 483 KB
• Volume: 97
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20627

✦ Synopsis

Micromolar concentrations (0.5 $ 5 mM) of all-trans geranylgeranoic acid (GGA) induced cell death in a guinea pig cell line, 104C1, whereas under the same conditions GGA was unable to kill 104C1/O4C, a clone established from 104C1 cells by transfection of them with the human phospholipid hydroperoxide glutathione peroxidase (PHGPx) gene. GGA (5 mM) induced a loss of the mitochondrial inner membrane potential (DCm) in 104C1 cells in 2 h, and their apoptotic cell death became evident in 6 h. On the other hand, 104C1/O4C cells were resistant to loss of DCm and showed intact morphology until at least 24 h after addition of 10 mM GGA. Dihydroethidine, superoxide-sensitive probe, was immediately oxidized 15 min after addition of GGA in both 104C1 and 104C1/O4C cells. The peroxide-sensitive probe 2 0 ,7 0 -dichlorofluorescin diacetate (H 2 -DCF-DA) was strongly oxidized in 104C1 cells 4 h after the addition of 2.5 mM GGA, but not in 104C1/O4C cells even in the presence of 10 mM GGA. The present results suggest that GGA induced a hyper-production of superoxide and subsequently peroxides, which in turn may have led to dissipation of the DCm and final apoptotic cell death in 104C1 cells.