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Cadmium inhibits the electron transfer chain and induces reactive oxygen species.

Authors
Wang-Y; Fang-J; Leonard-SS; Rao-KMK
Source
Free Radic Biol Med 2004 Jun; 36(11):1434-1443
NIOSHTIC No.
20024914
Abstract
Recent research indicates that cadmium (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 the stimulation of reactive oxygen species (ROS) production in mitochondria. The activity of complexes II (succinate:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome c oxidoreductase) 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 and in the absence of Cd. ESR showed that complex III might be the only site of ROS production induced by Cd. The results of kinetic studies and electron turnover experiments suggest that Cd may bind between semiubiquinone and cytochrome b566 of the Q0 site of cytochrome b of complex III, resulting in accumulation of semiubiquinones at the Q0 site. The semiubiquinones, being unstable, are prone to transfer one electron to molecular oxygen to form superoxide, providing a possible mechanism for Cd-induced generation of ROS in mitochondria.
Keywords
Cadmium-compounds; Free-radicals; Oxidative-processes; Oxidation; Cell-damage; Cellular-reactions; Cellular-function
Contact
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
CODEN
FRBMEH
CAS No.
7440-43-9
Publication Date
20040601
Document Type
Journal Article
Email Address
ybw4@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
11
ISSN
0891-5849
NIOSH Division
HELD
Source Name
Free Radical Biology and Medicine
State
WV
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