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Cadmium inhibits the activity of Complexes II and III of respiratory chain and induces ROS production in mitochondria.

Wang-YD; Fang-J; Leonard-S; Demchuk-E; Rao-KMK

FASEB J 2004 Mar; 18(5)(Suppl):A1196

https://www.fasebj.org/loi/fasebj

20031576

Cadmium (Cd), a non-transitional metal, is widely used in industry. The toxicities associated with cadmium are well known. Recent research indicates that Cd induces oxidative damage in cells; however, the mechanism of the oxidative stress induced by this metal is unclear. We investigated the effects of Cd on the individual complexes of the electron transfer chain (ETC) and on stimulation of reactive oxidative species production in mitochondria. The complexes studied are Complex I (NADH:Ubiquinone oxidoreductase), Complex II (Succinate:ubiquinone oxidoreductase), Complex III (Ubiquinol:cytochrome c oxidoreductase), and Complex IV (Cytochrome c oxidase). The activity of complexes II and III of mitochondrial ETC from liver, brain, and heart showed greater inhibition by Cd than the other complexes. Cd stimulated ROS production in the mitochondria of all three tissues mentioned above. The effect of various electron donors (NADH, succinate and 2,3-dimethoxy-5-methyl-6-decyl- 1,4-benzoquinol ) on ROS production was tested separately in the presence or absence of Cd. Results indicate that complex III is the only place that induces ROS in the presence of Cd. Results from kinetic studies and electron turnover experiments suggest that Cd may bind between semiubiquinoe and cytochrome b566 of the Qo site of cytochrome b of complex III. This binding will result in accumulation of semiubiquinones at the Qo site of complex III. The semiubiquinones are not stable and are prone to transfer one electron to molecular oxygen to form superoxide, providing a possible mechanism for Cd-induced generation of ROS in mitochondria.

Metal-compounds; Metal-industry; Cell-alteration; Cell-damage; Cell-growth; Cell-function; Cell-morphology; Cell-transformation; Cellular-reactions; Cellular-structures; Cellular-uptake; Cellular-transport-mechanism; Heart; Liver-cells; Liver-function; Liver-microsomal-metabolism; Brain-disorders

NIOSH, PPRB, HELD, Morgantown, WV 26505

FAJOEC

7440-43-9

20040324

Abstract; Conference/Symposia Proceedings

2004

5

0892-6638

HELD

The FASEB Journal. Experimental Biology 2004, Washington, DC, April 17-21, 2004

WV