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

2005 ◽  
Vol 97 (1) ◽  
pp. 178-187 ◽  
Author(s):  
Yoshihiro Shidoji ◽  
Kyoko Okamoto ◽  
Yasutoshi Muto ◽  
Sadaaki Komura ◽  
Nobuko Ohishi ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Peroxidase Gene ◽  
Phospholipid Hydroperoxide ◽  
Induced Apoptosis

Mitochondrial phospholipid hydroperoxide glutathione peroxidase inhibits the release of cytochrome c from mitochondria by suppressing the peroxidation of cardiolipin in hypoglycaemia-induced apoptosis

2000 ◽  
Vol 351 (1) ◽  
pp. 183-193 ◽  
Author(s):  
Kazuhiro NOMURA ◽  
Hirotaka IMAI ◽  
Tomoko KOUMURA ◽  
Toshihide KOBAYASHI ◽  
Yasuhito NAKAGAWA
Keyword(s):  
Cytochrome C ◽  
Glutathione Peroxidase ◽  
Acridine Orange ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Primary Event ◽  
Phospholipid Hydroperoxide ◽  
Cyt C ◽  
Mitochondrial Lipid ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

Cytochrome c (cyt. c) is a proapoptotic factor that binds preferentially to cardiolipin (CL), a mitochondrial lipid, but not to cardiolipin hydroperoxide (CL-OOH). Cyt. c that had bound to CL liposomes was liberated on peroxidation of the liposomes by a radical. The generation of CL-OOH in mitochondria occurred before the release of cyt. c in rat basophile leukaemia (RBL)2H3 cells that had been induced to undergo apoptosis by exposure to hypoglycaemia with 2-deoxyglucose (2DG). The amount of cyt. c bound to CL prepared from the mitochondria of 2DG-treated cells was lower than that of untreated cells. The release of cyt. c was completely suppressed when the production of CL-OOH in mitochondria was inhibited by the overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx). The fluorescence from CL-labelling dye (10-N-nonyl Acridine Orange) decreased on the induction of apoptosis by 2DG. However, no decrease in fluorescence was observed in PHGPx-overexpressing cells. Cyt. c was released from mitochondria that had been isolated from control cells on peroxidation by t-butylhydroperoxide, but no similar liberation of cyt. c from mitochondria isolated from mitochondrial PHGPx-overexpressing cells was observed. These findings suggest that the generation of CL-OOH in mitochondria might be a primary event that triggers the release of cyt. c from mitochondria in the apoptotic process in which mitochondrial PHGPx participates as an anti-apoptotic factor by preventing the formation of CL-OOH.

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