3 years ago

Mechanisms underlying aluminium neurotoxicity related to 14-3-3ζ protein.

Dai Cheng, Xiaomei Wang, Yuxia Ma, Weibo Jiang
Studies have shown aluminium (Al) is associated with Alzheimer's disease (AD) causality, however, the mechanism underlying this link remains unclear. To investigate the Al neurotoxicity, the high Al-affinity protein from pig hippocampus was screened by native gel electrophoresis and Al3+ plus 8-hydroxyquinoline (8-HQ) staining. The protein with high Al3+-affinity was identified to be 14-3-3ζ, which was then used for raising antibodies. By 8-HQ staining and immunocytochemical localization, we found the co-location of Al3+ and 14-3-3ζ increased markedly in the Al-exposed rat hippocampus tissue and the cultured rat primary hippocampal neuronal cells. By immune-analysis with antibodies against tau, we found tau accumulation mainly located in the neurons of cornu amonis3 and dentate gyrus of the rat hippocampus. Total free tau in hippocampus tissue and in neuronal cells increased 26.0% and 20.2%, respectively after Al-exposure. By immunofluorescent staining, we found the levels of tau and 14-3-3ζ co-location declined 15.9% or 12.1% in the hippocampus tissue or in neuronal cells after Al-exposure. These findings indicated that 14-3-3ζ combing with tau can prevent the over phosphorylation of tau and can be disturbed by Al-exposure due to Al3+ binding to 14-3-3ζ, which could account for the mechanisms underlying Al-neurotoxicity related to AD.

Publisher URL: http://doi.org/10.1093/toxsci/kfy021

DOI: 10.1093/toxsci/kfy021

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