Organoselenium compounds prevent hyperphosphorylation of cytoskeletal proteins induced by the neurotoxic agent diphenyl ditelluride in cerebral cortex of young rats.
In this work we investigated the protective ability of the selenium compounds ebselen and diphenyl diselenide against the effect of diphenyl ditelluride on the in vitro incorporation of 32P into intermediate filament (IF) proteins from slices of cerebral cortex of 17-day-old rats. We observed that ditelluride in the concentrations of 1, 15 and 50 microM induced hyperphosphorylation of the high-salt Triton insoluble neurofilament subunits (NF-M and NF-L), glial fibrillary acidic protein (GFAP) and vimentin, without altering the immunocontent of these proteins. Concerning the selenium compounds, diselenide (1,15 and 50 microM) did not induce alteration of the in vitro phosphorylation of the IF proteins. Otherwise, ebselen induced an altered in vitro phosphorylation of the cytoskeletal proteins in a dose-dependent manner. At intermediate concentrations (15 and 30 microM) it increased the in vitro phosphorylation even though, at low (5 microM) or high (50 and 100 microM) concentrations this compound was ineffective in altering the activity of the cytoskeletal-associated phosphorylating system. In addition, 15 microM diselenide and 5 microM ebselen, presented a protective effect against the action of ditelluride, on the phosphorylation of the proteins studied. Considering that hyperphosphorylation of cytoskeletal proteins is associated with neuronal dysfunction and neurodegeneration, it is probable that the effects of ditelluride could be related to the remarkable neurotoxicity of this organic form of tellurium. Furthermore the neuroprotective action of selenium compounds against tellurium effects could be a promising route to be exploited for a possible treatment of organic tellurium poisoning.
Moretto
M B
MB
Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Funchal
C
C
Zeni
G
G
Rocha
J B T
JB
Pessoa-Pureur
R
R
D000818:Animals; D001393:Azoles / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007382:Intermediate Filaments / Q000187:drug effects* / Q000378:metabolism; D054833:Isoindoles; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D001393:Azoles; D001555:Benzene Derivatives; D003598:Cytoskeletal Proteins; D054833:Isoindoles; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C061132:diphenyldiselenide; C042986:ebselen