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J.Health Sci., 47(1), 78-82, 2001

Cytochrome C Release from Mitochondria Induced by Cadmium

Masuo Kondoh, Satoko Ogasawara, Saeko Araragi, Minoru Higashimoto, and Masao Sato*

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan

Cadmium (Cd) induces apoptosis in vitro and in vivo. However, the mode of action is unclear. Cytochrome C (Cyt c) release from mitochondria into cytoplasm is a key event in apoptosis. In this study, we examined the effects of Cd on the release of Cyt c from mitochondria using human leukemia HL-60 cells and isolated mitochondria. Cd induced apoptosis in HL-60 cells in a dose-dependent manner, in accordance with increases in cytosolic Cyt c. Cd at 25 mu M also induced the release of Cyt c from isolated mitochondria. Mitochondrial swelling induced by permeability transition is known to cause outer membrane rupture and Cyt c release from mitochondria. Cd induced a swelling of mitochondria in vitro, as did calcium, a classical inducer of mitochondrial permeability transition. These results suggest that apoptosis induced by Cd appears to be involved in a mitochondria-dependent pathway and in the release of Cyt c from mitochondria by swelling.