Diphenyl ditelluride- and methylmercury-induced hyperphosphorilation of the high molecular weight neurofilament subunit is prevented by organoselenium compounds in cerebral cortex of young rats.
Organotellurides are important intermediates in organic synthesis and, consequently, the occupational exposure to them is a constant risk for laboratory workers. These compounds can elicit many neurotoxic events in the central nervous system (CNS) that are associated with several neurological symptoms. In contrast, organoselenium compounds are considered to exert neuroprotective actions on such effects. Neurofilaments (NF) are important cytoskeletal proteins and phosphorylation/dephosphorylation of NF is important to stabilize the cytoskeleton. In this work we investigated the potential protective ability of the selenium compounds ebselen and diphenyl diselenide (PhSe)(2) against the effect of diphenyl ditelluride (PhTe)(2) and methylmercury (MeHg) on the total (phosphorylated plus nonphosphorylated) and phosphorylated immunocontent of the high molecular weight neurofilament subunit (NF-H) from slices of cerebral cortex of 17-day-old rats. We observed that 1muM MeHg induced hyperphosphorylation, increasing the total immunocontent of this subunit of the high-salt Triton insoluble NF-H. Otherwise, 15muM (PhTe)(2) induced hyperphosphorylation of the high-salt Triton insoluble NF-H without altering the total immunocontent of this protein into the cytoskeletal fraction. Concerning the selenium compounds, 15muM (PhSe)(2) and 5muM ebselen did not induce alteration per se on the in vitro phosphorylation of NF-H. In addition, (PhSe)(2) and ebselen at these concentrations, presented a protective effect against the action of (PhTe)(2) and MeHg, on the immunoreactivity of NF-H. Considering that hyperphosphorylation of NF-H is associated with neuronal dysfunction it is probable that the effects of (PhTe)(2) and MeHg could be related to the remarkable neurotoxicity of these organocalcogenides. Furthermore the neuroprotective action of selenium compounds against (PhTe)(2) and MeHg effects could be a promising route to be exploited for a possible treatment of calcogenides poisoning.
Funchal
C
C
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Moretto
M B
MB
Vivian
L
L
Zeni
G
G
Rocha
J B T
JB
Pessoa-Pureur
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology* / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D054833:Isoindoles; D008767:Methylmercury Compounds / Q000633:toxicity*; D008970:Molecular Weight; D016900:Neurofilament Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009942:Organometallic Compounds / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D001393:Azoles; D001555:Benzene Derivatives; D054833:Isoindoles; D008767:Methylmercury Compounds; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C051774:neurofilament protein H; C061132:diphenyldiselenide; C042986:ebselen