title: Mitochondrial electron transport chain in heavy metal-induced neurotoxicity: effects of cadmium, mercury, and copper.
abstract: To clarify the role of mitochondrial electron transport chain (mtETC) in heavy-metal-induced neurotoxicity, we studied action of Cd(2+), Hg(2+), and Cu(2+) on cell viability, intracellular reactive oxygen species formation, respiratory function, and mitochondrial membrane potential of rat cell line PC12. As found, the metals produced, although in a different way, dose- and time-dependent changes of all these parameters. Importantly, Cd(2+) beginning from 10 [mu]M and already at short incubation time (3 h) significantly inhibited the FCCP-uncoupled cell respiration; besides, practically the complete inhibition of the respiration was reached after 3 h incubation with 50 [mu]M Hg(2+) or 500 [mu]M Cd(2+), whereas even after 48 h exposure with 500 [mu]M Cu(2+), only a 50% inhibition of the respiration occurred. Against the Cd(2+)-induced cell injury, not only different antioxidants and mitochondrial permeability transition pore inhibitors were protective but also such mtETC effectors as FCCP and stigmatellin (complex III inhibitor). However, all mtETC effectors used did not protect against the Hg(2+)- or Cu(2+)-induced cell damage. Notably, stigmatellin was shown to be one of the strongest protectors against the Cd(2+)-induced cell damage, producing a 15-20% increase in the cell viability. The mechanisms of the mtETC involvement in the heavy-metal-induced mitochondrial membrane permeabilization and cell death are discussed.
authors.affiliation: I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez pr. 44, 194223 Saint-Petersburg, Russia. alenab61@mail.ru
authors.forename: Elena A
authors.initials: EA
authors.lastname: Belyaeva
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Sokolova
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Emelyanova
authors.forename: Irina O
authors.initials: IO
authors.lastname: Zakharova
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D003300:Copper / Q000633:toxicity*; D004579:Electron Transport; D008628:Mercury / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002104:Cadmium; D003300:Copper; D008628:Mercury