Organochalcogens inhibit mitochondrial complexes I and II in rat brain: possible implications for neurotoxicity. 2013

Robson Luiz Puntel, and Daniel Henrique Roos, and Rodrigo Lopes Seeger, and Michael Aschner, and João Batista Teixeira Rocha
Universidade Federal do Pampa, Campus Uruguaiana BR-472 Km 7, Uruguaiana, RS 97500-970, Brazil. robson_puntel@yahoo.com.br

Organochalcogens, such as organoselenium and organotellurium compounds, can be neurotoxic to rodents. Since mitochondrial dysfunction plays a pivotal role in neurological disorders, the present study was designed to test the hypothesis that rat brain mitochondrial complexes (I, II, I-III, II-III and IV) could be molecular targets of organochalcogens. The results show that organochalcogens caused statistically significant inhibition of mitochondrial complex I activity, which was prevented by preincubation with NADH and fully blunted by reduced glutathione (GSH). Mitochondrial complex II activity remained unchanged in response to (PhSe)₂ treatment. Ebs and (PhTe)₂ caused a significant concentration-dependent inhibition of complex II that was also blunted by GSH. Mitochondrial complex IV activity was not modified by organochalcogens. Collectively, Ebs, (PhSe)₂ and (PhTe)₂ were more effective inhibitors of brain mitochondrial complex I than of complex II, whereas they did not affect complex IV. These observations are consistent with organochalcogens inducing mitochondrial complex I and II inhibition via their thiol-oxidase-like activity, with Ebs, (PhSe)₂ and (PhTe)₂ effectively oxidising critical thiol groups of these complexes.

UI MeSH Term Description Entries
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016566 Organoselenium Compounds Organic compounds which contain selenium as an integral part of the molecule. Compounds, Organoselenium
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D042963 Electron Transport Complex II A flavoprotein oxidase complex that contains iron-sulfur centers. It catalyzes the oxidation of SUCCINATE to fumarate and couples the reaction to the reduction of UBIQUINONE to ubiquinol. Succinate Dehydrogenase (Ubiquinone),Succinate Dehydrogenase-CoQ Reductase,Succinate Dehydrogenase-Coenzyme Q Reductase,Succinate-Coenzyme Q Reductase,Succinate-Q Oxidoreductase,Succinate-Quinone Oxidoreductase,Succinate-Ubiquinone Oxidoreductase,Succinate-Ubiquinone Reductase,Dehydrogenase-CoQ Reductase, Succinate,Oxidoreductase, Succinate-Q,Oxidoreductase, Succinate-Quinone,Oxidoreductase, Succinate-Ubiquinone,Reductase, Succinate Dehydrogenase-CoQ,Succinate Coenzyme Q Reductase,Succinate Dehydrogenase CoQ Reductase,Succinate Dehydrogenase Coenzyme Q Reductase,Succinate Q Oxidoreductase,Succinate Quinone Oxidoreductase,Succinate Ubiquinone Oxidoreductase,Succinate Ubiquinone Reductase
D042967 Electron Transport Complex I A flavoprotein and iron sulfur-containing oxidoreductase complex that catalyzes the conversion of UBIQUINONE to ubiquinol. In MITOCHONDRIA the complex also couples its reaction to the transport of PROTONS across the internal mitochondrial membrane. The NADH DEHYDROGENASE component of the complex can be isolated and is listed as EC 1.6.99.3. NADH Dehydrogenase (Ubiquinone),Complex I Dehydrogenase,NADH DH I,NADH Dehydrogenase Complex 1,NADH Dehydrogenase I,NADH Q1 Oxidoreductase,NADH-CoQ Reductase,NADH-Coenzyme Q Reductase,NADH-Ubiquinone Oxidoreductase,NADH-Ubiquinone Reductase,Respiratory Complex I,Rotenone-Sensitive Mitochondrial NADH-Ubiquinone Oxidoreductase,Ubiquinone Reductase,Dehydrogenase, Complex I,NADH CoQ Reductase,NADH Coenzyme Q Reductase,NADH Ubiquinone Oxidoreductase,NADH Ubiquinone Reductase,Oxidoreductase, NADH Q1,Oxidoreductase, NADH-Ubiquinone,Reductase, NADH-Ubiquinone,Rotenone Sensitive Mitochondrial NADH Ubiquinone Oxidoreductase
D051336 Mitochondrial Membranes The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE). Inner Mitochondrial Membrane,Mitochondrial Membrane, Inner,Mitochondrial Membrane, Outer,Outer Mitochondrial Membrane,Inner Mitochondrial Membranes,Membrane, Inner Mitochondrial,Membrane, Mitochondrial,Membrane, Outer Mitochondrial,Membranes, Inner Mitochondrial,Membranes, Mitochondrial,Membranes, Outer Mitochondrial,Mitochondrial Membrane,Mitochondrial Membranes, Inner,Mitochondrial Membranes, Outer,Outer Mitochondrial Membranes
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018011 Chalcogens The elements OXYGEN; POLONIUM; SELENIUM; SULFUR; and TELLURIUM; that form group 16 (formerly group VI) of the periodic table. Group 16 Elements,Elements, Group 16

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