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-X-L 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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.Pharmacology & PharmacyToxicologySCI(E)PubMed0ARTICLE1-219-3319
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