Cadmium directly induced the opening of membrane permeability pore of mitochondria which possibly involved in cadmium-triggered apoptosis.
The mitochondrial damage induced by cadmium has been well established, but its mechanism and its relationship with cadmium-induced apoptosis are elusive until now. Our research showed that cadmium could directly lead to the dysfunction of isolated mitochondria from mouse liver, including the inhibition of respiration, the opening of permeability transition pore (PTP), the loss of transmembrane potential, and the release of cytochrome c. These mitochondrial changes were completely suppressed by Bcl-xL and Ruthenium Red (RR). Bongkrekic acid (BK), an inhibitor of the PTP opening directly via adenine nucleotide translocator (ANT), also completely inhibited the PTP opening and loss of transmembrane potential. However, cyclosporin A (CsA), another inhibitor of the PTP opening indirectly via ANT, had not any inhibitory effect. When cadmium being pre-incubated with proteins containing abundant thiol groups, its effect was partially reversed. These results revealed that mitochondria pathway may involve in cadmium-induced apoptosis, and cadmium caused the PTP opening possibly through its binding to thiol groups of ANT. Furthermore, the mechanism of the PTP opening induced by cadmium was probably distinct from that of the calcium-induced PTP opening.
Li
Min
M
Department of Toxicology, Health Science Center, Peking University, Beijing 100083, PR China.
Xia
Tian
T
Jiang
Chun-Sun
CS
Li
Lin-Jiang
LJ
Fu
Juan-Ling
JL
Zhou
Zong-Can
ZC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001865:Bongkrekic Acid / Q000494:pharmacology; D002104:Cadmium / Q000633:toxicity*; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010101:Oxygen Consumption / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D002104:Cadmium; D001865:Bongkrekic Acid; D012430:Ruthenium Red; D016572:Cyclosporine; D045304:Cytochromes c