title: Reversible inhibition of hydrogen peroxide elimination by calcium in brain mitochondria.
abstract: In the present work, the Ca(2+) dependence of mitochondrial H(2) O(2) elimination was investigated. Mitochondria isolated from guinea pig brain were energized by glutamate and malate and incubated with micromolar concentrations of Ca(2+) in the presence of ADP, preventing permeability transition pore formation. After the completion of Ca(2+) uptake, mitochondria were challenged with H(2) O(2) (5 μM), then at various time points residual H(2) O(2) was determined using the Amplex red method and compared with that in mitochondria incubated with H(2) O(2) without Ca(2+) addition. Dose-dependent inhibition of H(2) O(2) elimination by Ca(2+) was detected, which was prevented by the Ca(2+) -uptake inhibitor Ru 360. Stimulation of Ca(2+) release from Ca(2+) -loaded mitochondria by a combined addition of Ru 360 and Na(+) decreased the Ca(2+) -evoked inhibition of H(2) O(2) removal. After Ca(2+) uptake (50 μM), mitochondrial aconitase activity was found to be decreased, which was partially attributable to the impaired elimination of endogenously produced reactive oxygen species. We found that the effects of Ca(2+) and H(2) O(2) on the activity of aconitase were additive. These results confirm that Ca(2+) inhibits elimination of H(2) O(2) in mitochondria and demonstrate that this effect is concentration dependent and reversible. The phenomenon described here can play a role in the modulation of ROS handling under conditions involving excessive cellular Ca(2+) load.
authors.affiliation: Department of Medical Biochemistry, Semmelweis University, and Laboratory of Neurobiochemistry and Molecular Physiology, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tretter
authors.forename: Emanuela
authors.initials: E
authors.lastname: Biagioni Angeli
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ardestani
authors.forename: Gianfrancesco
authors.initials: G
authors.lastname: Goracci
authors.forename: Vera
authors.initials: V
authors.lastname: Adam-Vizi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002118:Calcium