TY - JOUR
T1 - Organochalcogens inhibit mitochondrial complexes i and ii in rat brain
T2 - Possible implications for neurotoxicity
AU - Puntel, Robson Luiz
AU - Roos, Daniel Henrique
AU - Seeger, Rodrigo Lopes
AU - Aschner, Michael
AU - Rocha, João Batista Teixeira
N1 - Funding Information:
Acknowledgments This work was supported by grants from UNIPAMPA (Universidade Federal do Pampa), UFSM (Universidade Federal de Santa Maria), FAPERGS (Fundac¸ão de Amparo a Pesquisa do Estado do Rio Grande do Sul), CAPES (Coordenac¸ão de Aper-feic¸oamento de Pessoal de Nível Superior), CNPq (Conselho Nac-ional de Desenvolvimento Científico e Tecnológico), FINEP (Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00) and INCT-EN (Instituto Nacional de Ciência e Tecnologia em Excito-toxicidade e Neuroprotec¸ão). MA was supported in part by Grants from the National Institutes of Health ES R01 07331, ES R011 0563 and ES P30 000267.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Brain mitochondria
KW - Molecular target
KW - Thiol oxidation
KW - Thiol-oxidase-like activity
UR - http://www.scopus.com/inward/record.url?scp=84984589049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84984589049&partnerID=8YFLogxK
U2 - 10.1007/s12640-012-9365-0
DO - 10.1007/s12640-012-9365-0
M3 - Article
AN - SCOPUS:84984589049
SN - 1029-8428
VL - 24
SP - 109
EP - 118
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 2
ER -