Cupric nitrilotriacetate-induced apoptosis in HL-60 cells association with lipid peroxidation, release of cytochrome C from mitochondria, and activation of caspase-3.
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| Abstract |
Oxidative stress may be a common mechanism underlying various forms of cell death, including necrosis and apoptosis. The authors have reported previously that the cupric nitrilotriacetate (Cu-NTA), a renal carcinogen, induces oxidative DNA damage and apoptosis in HL-60 human leukemia cells (Ma, Y., et al. Free Radic. Biol Med. 25:568-575; 1998). The focus of this investigation was to examine the possible pathway of the apoptosis induced by Cu-NTA. Results of the present study demonstrated that after exposure of HL-60 cells to Cu-NTA, an increase in lipid hydroperoxide and loss of mitochondrial membrane potential (deltaphim) were observed, followed by the increase in cytosolic cytochrome c that was released from the mitochondria. These events proceeded and triggered the activation of caspase-3 (CPP32/apopain/Yama), resulting in the degradation of poly (ADP-ribose) polymerase and DNA fragmentation. The antioxidants, N-acetylcysteine and glutathione, protected the loss of deltaphim and blocked the apoptosis induced by Cu-NTA. In addition, Ac-DEVD-CHO, a specific inhibitor of caspase-3, inhibited Cu-NTA-induced apoptosis. These results suggested that Cu-NTA-induced apoptosis in HL-60 cells was, at least in part, triggered by free radical-induced lipid peroxidation of membrane, which induced the release of cytochrome c from mitochondria and activation of caspase-3.
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| Authors | Y Ma, T Ogino, T Kawabata, J Li, K Eguchi, S Okada |
| Journal | Free radical biology & medicine (Free Radic Biol Med) Vol. 27 Issue 1-2 Pg. 227-33 (Jul 1999) ISSN: 0891-5849 [Print] United States |
| PMID | 10443940 (Publication Type: Journal Article) |
| Chemical References |
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