Funchal C, Moretto M B, Vivian L, Zeni G, Rocha J B T, Pessoa-Pureur R
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Toxicology. 2006 May 1;222(1-2):143-53. doi: 10.1016/j.tox.2006.02.009. Epub 2006 Mar 6.
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.
有机碲化物是有机合成中的重要中间体,因此,实验室工作人员在职业中接触它们始终存在风险。这些化合物可在中枢神经系统(CNS)引发许多神经毒性事件,并伴有多种神经症状。相比之下,有机硒化合物被认为对这些影响具有神经保护作用。神经丝(NF)是重要的细胞骨架蛋白,NF的磷酸化/去磷酸化对于稳定细胞骨架很重要。在这项工作中,我们研究了硒化合物依布硒啉和二苯基二硒醚(PhSe)₂对二苯基二碲醚(PhTe)₂和甲基汞(MeHg)对17日龄大鼠大脑皮质切片中高分子量神经丝亚基(NF-H)的总(磷酸化加非磷酸化)和磷酸化免疫含量的影响的潜在保护能力。我们观察到,1μM MeHg诱导了过度磷酸化,增加了高盐Triton不溶性NF-H该亚基的总免疫含量。否则,15μM(PhTe)₂诱导高盐Triton不溶性NF-H的过度磷酸化,而不会改变该蛋白在细胞骨架部分的总免疫含量。关于硒化合物,15μM(PhSe)₂和5μM依布硒啉本身不会诱导NF-H的体外磷酸化发生改变。此外,这些浓度的(PhSe)₂和依布硒啉对(PhTe)₂和MeHg对NF-H免疫反应性的作用具有保护作用。考虑到NF-H的过度磷酸化与神经元功能障碍有关,(PhTe)₂和MeHg的作用可能与这些有机金属化合物的显著神经毒性有关。此外,硒化合物对(PhTe)₂和MeHg作用的神经保护作用可能是一条有前途的途径,可用于开发可能的硫属化物中毒治疗方法。