title: Spectroscopic and microscopic studies on the mechanisms of mitochondrial toxicity induced by different concentrations of cadmium.
abstract: The deleterious action of Cd2+ on rat liver mitochondria was investigated in this work using spectroscopic and microscopic methods. The concentration dependence of Cd2+ on mitochondrial swelling, membrane potential and membrane fluidity was studied. Our aim was to detect the active sites of Cd2+ in the mitochondrial membrane treatments with cyclosporin A (CsA) and EGTA on the mitochondrial permeability transition (MPT) induced by low and high concentrations of Cd2+. The protective effects of dithiothreitol, human serum albumin and monobromobimane+ on Cd2+-induced MPT were also monitored. All of these investigations indicated that Cd2+ can directly affect MPT at two separate localization sites at different concentrations: the classic Ca2+ triggering site and the thiol (-SH) groups of membrane proteins matched by MPT pore opening (defined as "S" site). At the high concentration of Cd2+, other free -SH groups in the mitochondrial matrix may be involved in this process. These findings were supported by transmission electron microscopy and shed light on the toxic mechanism of Cd2+ on mitochondria.
authors.affiliation: State Key Laboratory of Virology, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jia-Han
authors.initials: JH
authors.lastname: Li
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Feng-Lei
authors.initials: FL
authors.lastname: Jiang
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Tian
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D005454:Fluorescence Polarization; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats; D017208:Rats, Wistar
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002104:Cadmium