Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial permeability transition through thiol-oxidation.
Selenium is an essential trace element in mammals and is thought to play a chemopreventive role in human cancer, possibly by inducing tumor cell apoptosis. Mitochondria play a pivotal role in the induction of apoptosis in many cell types. The effects of selenite on mitochondrial function were therefore investigated. Selenite induced the oxidation and cross-linking of protein thiol groups, mitochondrial permeability transition (MPT), a decrease in the mitochondrial membrane potential, and the release of cytochrome c in mitochondria isolated from rat liver. Induction of the MPT by selenite was prevented by cyclosporin A, EGTA, or N-ethylmaleimide. These results thus indicate that selenite induces the MPT as a result of direct modification of protein thiol groups, resulting in the release of cytochrome c and a loss of mitochondrial membrane potential.
Kim
Tae-soo
TS
Laboratory of Cellular and Molecular Biochemistry, Graduate School of Biotechnology, Korea University, 1 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-701, Republic of Korea.
Jeong
Dae-won
DW
Yun
Byung Yup
BY
Kim
Ick Young
IY
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D018038:Sodium Selenite / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D016588:Anticarcinogenic Agents; D003574:Cytochrome c Group; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D013438:Sulfhydryl Compounds; D013481:Superoxides; D018038:Sodium Selenite