title: Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition.
abstract: Mitochondrial permeability transition (MPT) is correlated with the opening of a nonspecific pore, the so-called transition pore, that triggers bidirectional traffic of inorganic solutes and metabolites across the mitochondrial membrane. This phenomenon is caused by supraphysiological Ca(2+) concentrations and by other compounds leading to oxidative stress, while cyclosporin A, ADP, bongkrekic acid, antioxidant agents and naturally occurring polyamines strongly inhibit it. The effects of polyamines, including the diamine agmatine, have been widely studied in several types of mitochondria. The effects of monoamines on MPT have to date, been less well-studied, even if they are involved in a variety of neurological and neuroendocrine processes. This study shows that in rat liver mitochondria (RLM), monoamines such as tyramine, serotonin and dopamine amplify the swelling induced by calcium, and increase the oxidation of thiol groups and the production of hydrogen peroxide, effects that are counteracted by the above-mentioned inhibitors. In rat brain mitochondria (RBM), the monoamines do not amplify calcium-induced swelling, even if they demonstrate increases in the extent of oxidation of thiol groups and hydrogen peroxide production. In these mitochondria, the antioxidants are not at all or scarcely effective in suppressing mitochondrial swelling. In conclusion, we hypothesize that different mechanisms induce the MPT in the two different types of mitochondria evaluated. Calcium and monoamines induce oxidative stress in RLM, which in turn appears to induce and amplify MPT. This process is not apparent in RBM, where MPT seems resistant to oxidative stress.
authors.affiliation: Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Grancara
authors.forename: Valentina
authors.initials: V
authors.lastname: Battaglia
authors.forename: Pamela
authors.initials: P
authors.lastname: Martinis
authors.forename: Nikenza
authors.initials: N
authors.lastname: Viceconte
authors.forename: Enzo
authors.initials: E
authors.lastname: Agostinelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Toninello
authors.forename: Renzo
authors.initials: R
authors.lastname: Deana
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010539:Permeability; D051381:Rats
chemical_list: D015306:Biogenic Monoamines; D002118:Calcium